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NATIONAL GUIDELINES

FOR
PAEDIATRIC HIV AND AIDS
TREATMENT AND CARE

FEDERAL MINISTRY OF HEALTH


NIGERIA
2007
COPY RIGHT PAGE

ISBN Number……..

FEDERAL MINISTRY OF HEALTH


NIGERIA
2007

1
LIST OF CONTRIBUTORS

NAMES ORGANISATION/ADDRESS
Prof. Kike Osinusi Department of Paediatrics, UCH, Ibadan
Prof. W. N. Ogala Department of Paediatrics, ABUTH, Zaria
Dr. Edna Iroha Department of Paediatrics, LUTH, Idi-Araba,
Lagos
Dr. A. I. Rabasa Department of Paediatrics, UMTH, Maiduguri
Dr. A. Nte Department of Paediatrics, UPTH, Port Harcourt
Dr. E. A. Adejuyigbe Department of paediatrics, OAUTH, Ile-Ife
Dr. S. Oguche Department of Paediatrics, JUTH, Jos
Dr. S. D. Pam Department Paediatrics, JUTH, Jos
Dr. L.W. Umar Department of Paediatrics, ABUTH, Zaria
Dr. Isaac Elon Department of Paediatrics, FMC, Gombe
Dr. Kolade Ernest Department of Paediatrics, UITH, Ilorin
Dr. O. Oniyangi Department of Paediatrics, National Hospital,
Abuja
Dr. Mariya Mukhtar-Yola Department of Paediatrics, AKTH, Kano
Dr. O.A. Owolabi Department of Paediatrics, UITH, Ilorin
Dr. J.U. Ojukwu Department of Paediatrics, EBSU, Abakaliki
Dr. G. Eke Department of Paediatrics, UPTH, Port Harcourt
Dr. Abieyuwa Emokpae Massey Street Children’s Hospital, Lagos
Dr. Rosemary Audu NIMR, Lagos
Dr. Georgina Odaibo Department of Virology, UCH, Ibadan
Dr. Pat Matemilola NEPWHAN, Abuja
Dr. Abiola Davies UNICEF, Abuja
Dr. Tunde Adegboyega WHO, Abuja
Dr. Pyande Mongi WHO, Abuja
Dr. Niyi Ogundiran WHO, Abuja
Dr. N. Sani-Gwarzo CDC, Abuja
Dr. E. O. Jaiyesimi CDC, Abuja
Dr. C. Omeogu USAID, Abuja
Dr. O. Ibe USAID, Abuja

2
Dr. Sunny Ochigbo APIN PLUS/Harvard PEPFAR, Lagos
Dr. J. Mafeni ENHANSE/CCM, Abuja
Dr. Shafiq Essajee Clinton Foundation, Abuja
Mr. Stephen Kisayke Clinton Foundation, Abuja
Dr. L. Anomnachi Clinton Foundation, Abuja
Prof. John Farley IHV-Nigeria, Abuja
Dr. David Bowman IHV-Nigeria, Abuja
Dr. M. J. Gambo IHV-Nigeria, Abuja
Dr. Orode Doherty ICAP Nigeria, Abuja

FMOH STAFF
Dr. A. Akinsete HIV and AIDS Division
Dr. O. Salawu HIV and AIDS Division
Dr. Evelyn Ngige HIV and AIDS Division
Dr. A. Lawanson HIV and AIDS Division
Dr. A. Adedeji HIV and AIDS Division
Dr. L Uzono HIV and AIDS Division
Dr. D. Bako HIV and AIDS Division
Dr. Emi Monye HIV and AIDS Division
Dr. B. Ibrahim HIV and AIDS Division
Mrs. O. F. Adegoke HIV and AIDS Division
Mr. S. A.Egbewumi HIV and AIDS Division
Mrs Ima Dada HIV and AIDS Division
Mrs. O. A .J. Adebari HIV and AIDS Division
Mr. O. A. Ombungadu HIV and AIDS Division
Dr. Olurunfemi. Amoran HIV and AIDS Division

3
ACKNOWLEDGMENTS

The Federal Ministry of Health appreciates the dedication and commitment of all
those who contributed in various ways to the development and production of this
document.

The development of these guidelines was made possible with the support of our
partners especially UNICEF and Clinton Foundation. Their continued support and
technical assistance are highly appreciated.

The contributions of all the former and current Directors of Public Health, National
Coordinators and staff of the National AIDS/STIs Control Programme are highly
appreciated.

Dr Ngozi Njepuome
Director Public Health
Federal Ministry of Health

4
FOREWORD

Twenty-six years after the first case of Acquired Immunodeficiency Syndrome


(AIDS) was diagnosed, the Human Immunodeficiency Virus and Acquired
Immunodeficiency Syndrome (HIV and AIDS) pandemic is now widely recognised as
a major public health crisis which affects not only the lives of individuals, but also the
future socio-economic development of nations.

The HIV and AIDS pandemic disproportionately affect children and young adults. It
is now an increasingly important cause of childhood morbidity and mortality in many
African countries including Nigeria and has slowed down or reversed the gains of the
child survival efforts of the last decade. This has become even more significant
because children profoundly depend on adults, not only for physical and emotional
needs, but also for the formulation and implementation of policies and programmes
that affect their survival and development.

In Nigeria it is estimated that one HIV-exposed child is born every five minutes. In
recognition of the magnitude of the HIV and AIDS problem in Nigeria, the Federal
Government has put in place a multi-sectoral response to prevent and control the
epidemic. Part of this effort is the Health Sector Response being implemented by the
Federal Ministry of Health.

The development of these guidelines is part of the treatment, care and support
strategies of the Health sector for the implementation of the Paediatric HIV and AIDS
Initiative. The guidelines provide essential and relevant information needed by health
workers not only to understand paediatric HIV and AIDS, but also to control and
manage it. The Government expects that all those providing care for children with
HIV and AIDS will strive to attain the standards prescribed in these guidelines.

Professor Eyitayo Lambo


Honourable Minister of Health

5
ABOUT THE GUIDELINES
The Federal Ministry of Health with the assistance of UNICEF in 2003 developed the
first draft of the National Guidelines for the Management of Paediatric HIV and
AIDS, in response to increasing paediatric HIV and AIDS and the neglect of children
in the National HIV programme. This is part of the multi-sectoral response of the
Federal Government to the HIV pandemic. Although the final print of that document
was not produced, it provided the template for the inclusion of paediatric HIV and
AIDS management in the 2005 Guidelines for the Use of Antiretroviral (ARV) Drugs
in Nigeria. However the 2005 Guidelines was considered inadequate in many aspects
of paediatric HIV care. This realisation, in addition to the recent information on HIV
and AIDS necessitated the current review of the document.

The Guidelines provide current evidence-based scientific information on paediatric


HIV and AIDS. It reviews the epidemiology, pathophysiology, clinical features,
management and prevention of HIV and AIDS including associated conditions e.g.
Tuberculosis (TB) co-infection. The legal and ethical issues related to HIV and AIDS
are also briefly discussed.

It is written for healthcare providers at all levels responsible for the care of children
both in public and private sectors. It will provide information for the implementation
of the Paediatric HIV and AIDS programme throughout the country. Since situations
at different levels of care vary, users should adapt it to their settings. It will facilitate
the scale up of treatment, care and support of children infected with HIV and AIDS.

In the use of these Guidelines, health care providers at all levels must realize the need
to establish linkages with pre-existing programmes to ensure efficient use of
resources. Linkages with the following programmes will therefore need to be
established (Fig. i.).

• The Prevention of Mother-to-Child Transmission of HIV (PMTCT)


• The Adult Antiretroviral Therapy (ART)
• The HIV Counselling and Testing(HCT)
• Home-Based care (HBC) for HIV-infected persons

6
• Orphans and Vulnerable Children (OVC)
• Integrated Maternal, Newborn and Child Health
• School Health

COMMUNITY
SUPPORT • ADULT ART
INTEGRATED
PROGRAMMES PROGRAMME
MATERNAL,
INCLUDING • HCT SERVICES
NEWBORN AND
HOME-BASED • TB AND OTHER
CHILD HEALTH
CARE SPECIALISED
SERVICES
CLINICS

PREVENTION OF PAEDIATRIC
ADOLESCENT
MOTHER-TO- HIV AND AIDS
AND YOUTH
CHILD TREATMENT,
HEALTH
TRANSMISSION CARE AND
SERVICES
SERVICES SUPPORT
PROGRAMME

ORPHANS AND
SCHOOL HEALTH VULNERABLE
PROGRAMME PAEDIATRIC OUT- CHILDREN’S
AND OTHERS PATIENT AND PROGRAMME
IN-PATIENT SERVICES
SERVICES

Fig. i. Linkages between paediatric HIV and AIDS and other programmes

7
TABLE OF CONTENTS
Page
List of contributors ...................................................................................................................... I
Acknowledgements ...................................................................................................................... III
Foreword ...................................................................................................................... IV
About the Guidelines ...................................................................................................................... V
Table of contents ...................................................................................................................... VII
List of figures ...................................................................................................................... IX
List of tables ...................................................................................................................... X
List of annexes ...................................................................................................................... XII
Acronyms ...................................................................................................................... XIII
Chapter 1: Introduction ...................................................................................................................... 1
Chapter 2: Virology ......................................................................................................................

2.1 Classification and structure


22. Variability of HIV isolates
2.3 Cellular receptors
2.4 Replication
2.5 Natural history in children below 6 years
2.6 Natural history of HIV infection in children ≥ 6 years
2.7 Factors predicting prognosis
Chapter 3: Diagnosis of HIV and AIDS ...................................................................

3.1 Clinical presentation


3.2 Approach to diagnosis
3.3 Laboratory diagnosis of HIV infection
3.4 Diagnosis in children
3.5 Assessment and monitoring of severity of HIV
infection and disease progression ..................................................................

3.6 Counselling in paediatric HIV and AIDS


3.7 Paediatric disclosure (talking to children about their
HIV status)
Chapter 4: Provider-Initiated Testing and Counselling (PITC)
4.1 Recommendations for PITC in Children and Adolescent Health care
services

8
4.2 Pre-test information and informed consent for PITC in Children and
Adolescents
4.3 Guiding principles and Special Considerations in adopting PITC
strategy for Children
4.4 Special Considerations in PITC for Adolescents
4.5 Follow-up of Children and Adolescents where a test is declined
4.6 Post-test counselling for HIV-positive persons
4.7 Post-test counselling for HIV-positive pregnant women
4.8 Linkages and Referrals to other HIV services
4.9 Frequency of testing
Chapter 5: Management of common clinical conditions
associated with paediatric HIV and AIDS ...............................

Chapter 6: Common opportunistic and co-infections ...............................

6.1 Tuberculosis
6.2 Hepatitis B and C
Chapter 7: Antiretroviral therapy ...........................................................................

7.1 Principles of antiretroviral therapy


7.2 Classes of ARVs
7.3 Initiating ARV therapy
7.4 Antiretroviral drug toxicity
7.5 Drug interaction
7.6 Substitution within the first line ARV drug regimens in
infants and children
7.7 Treatment failure in infants and children
7.8 Switching ARV regimen in infants and children
7.9 Treatment interruption
7.10 Discontinuation of therapy
7.11 Salvage therapy
7.12 Drug resistance
7.13 Adherence to ART
Chapter 8: Clinical and laboratory monitoring ......................................................

8.1 Baseline clinical and laboratory assessment


8.2 Routine monitoring of children who are not yet
eligible for ART

9
8.3 Routine monitoring of children on ART
Chapter 9: Supportive care ...........................................................................

9.1 Definitions and Context


9.2 Food/Nutrition in HIV and AIDS
9.3 Psychosocial support (PSS)
9.4 Education and Vocational Training
9.5 Health care needs of OVC
9.6 Protection including Legal Support
9.7 Shelter
9.8 Economic Strengthening
Chapter 10: HIV infection in adolescents ...........................................................................

10.1 Transmission
10.2 Clinical features, diagnosis and management of HIV in adolescents
10.3 Antiretroviral therapy
10.4 Challenges related to HIV and AIDS in adolescents
10.5 Counselling for ART in adolescents
10.6 Prevention
Chapter 11: Prevention of HIV infection ...........................................................................

11.1 Specific strategies for prevention of HIV infection in children


11.2 Post-exposure prophylaxis for children
11.3 Post-sexual exposure prophylaxis
Chapter 12: Legal and ethical issues ........................................................................

12.1 Children and the law


Chapter 13: Programmatic Monitoring and Evaluation
13.1 Indicators to track the Paediatric ART programme
13.2 Paediatric ART Management Information System (ART MIS)
13.4 Data flow
13.5 Data Analysis and Reporting
13.6 Project management meeting

Annexes

10
LIST OF FIGURES
Page
Figure i. The Linkages between Paediatric HIV and AIDS and other
programmes
Figure 1.1. Median National (Nigeria) HIV Prevalence trend
Figure 2.1. Simplified schematic structure of HIV
Figure 2.2. Genomic structure of a typical HIV-1
Figure 2.3. HIV replication cycle
Figure 2.4. Dynamics of virus and CD4+ levels over the course of an
untreated HIV infection
Figure 2.5. Natural course of viral load and anti-HIV antibody
in adults and children
Figure 3.1. Algorithm for Early Infant Diagnosis of HIV infection
Figure 7.1. Life cycle of HIV showing the point of action of ARVs.

11
LIST OF TABLES
Page
Table 2.1: Factors predicting disease progression in infants
Table 3.1: Neurologic manifestations of paediatric HIV infection
Table 3.2: Clinical signs or conditions in a child that may suggest
HIV infection
Table 3.3: WHO staging system for HIV infection and disease in
infants, children and adolescents
Table 3.4: Presumptive and definitive criteria for recognizing HIV-related
clinical events in infants and children with established
HIV infection
Table 3.5: WHO classification of HIV-associated immunodeficiency

in infants and children

Table 4.1: HIV-related services recommended for implementation of


comprehensive provider-initiated HIV testing and counselling
in health facilities
Table 5.1: Common childhood infections in HIV and AIDS
Table 6.1: Common opportunistic infections in children with
HIV and AIDS
Table 6.2: Features and treatment of hepatitis B and C infections in
children with HIV and AIDS
Table 7.1: Antiretroviral drugs
Table 7.2: Nucleoside Reverse Transcriptase Inhibitors
Table 7.3: Non-Nucleoside Reverse Transcriptase Inhibitors
Table 7.4: Protease Inhibitors
Table 7.5: Dosing schedule for Fixed-Dose Combination containing
d4T/3TC/NVP
Table 7.6: First line ARV regimen
Table 7.7: Timing of ART following initiation of TB treatment with
rifampicin-containing regimen in HIV infected infants
and children
Table 7.8: Management of TB/HIV co-infection in children developing
TB while on ARVs

12
Table 7.9: Antiretroviral drug toxicity
Table 7.10: Drug interactions
Table 7.11: Severe toxicities associated with specific first line ARVs
and potential first line drug substitution
Table 7.12: Second line ARV regimens
Table 8.1: Schedule for starting and monitoring children on HAART
Table 8.2: Tiered laboratory capabilities for HIV treatment
Table 9.1: Recommended immunization schedule for use in
HIV-exposed or infected children
Table 9.2: Symptoms of common illnesses, causes and their management
Table 9.3: Weight-based dosage in co-trimoxazole prophylaxis for
children
Table 11.1: Recommended drug regimen for post-exposure prophylaxis
Table 11.2: Recommended schedule of investigations following exposure
Table 13.1: Paediatric ART Programme Core indicators
Table 13.2: Service statistics for Paediatric ART Programme

13
ANNEXES
Page
ANNEX I: Paediatric weight-based dosing chart
ANNEX II a: Tanner Sexual Maturity Staging in females
ANNEX II b: Tanner Sexual Maturity Staging in males

14
ACRONYMS
3TC Lamivudine
ABC Abacavir
AFASS Affordable, Feasible, Available, Sustainable, Safe
AFB Acid Fast Bacilli
AIDS Acquired Immunodeficiency Syndrome
ALT Alanine aminotransferase
ANC Antenatal clinic
APV Amprenavir
ARV Antiretroviral
ART Antiretroviral Therapy
ARM Artificial rupture of membrane
AZT Azidothymidine (Zidovudine)
AZV Atazanavir
BCG Bacillé- Calmette-Guerin
BF Breastfeeding
BFHI Baby Friendly Hospital Initiative
BMS Breastmilk Substitute
CBOs Community-Based Organisations
CCM Country Coordinating Mechanism
CDC Centre for Disease Control and Prevention
CD4+ T lymphocyte bearing CD4+ marker
CMV Cytomegalovirus
CNS Central nervous system
CPK Creatinine phosphokinase
CPT Co-trimoxazole Preventive Therapy
CSF Cerebrospinal Fluid
CSM Cerebrospinal meningitis
CT Computerized Tomography
CTX Co-trimoxazole
d4T Stavudine
DBS Dried Blood Spot
DIC Disseminated Intravascular Coagulopathy

15
ddC Zalcitabine
DDI Didanosine
DLV Delavirdine
EBF Exclusive Breastfeeding
EEG Electroencephalography
EFV Efavirenz
EGA Estimated Gestational Age
EID Early Infant Diagnosis
ELISA Enzyme-linked Immunosorbent Assay
EMG Electromyography
ENT Ear Nose and Throat
ESR Erythrocyte Sedimentation Rate
FBC Full Blood Count
FBO Faith-Based Organization
FMOH Federal Ministry of Health
FP Family Planning
FTC Emtricitabine
GHAIN Global HIV/AIDS Initiative in Nigeria
G-CSF Granulocyte Colony Stimulating Factor
HAART Highly Active Antiretroviral Therapy
HBV Hepatitis B virus
HBcAg Hepatitis core antigen
HCVAb Hepatitis C antibody
HBeAg Hepatitis B e antigen
HBsAg Hepatitis B surface antigen
HCT HIV Counselling and Testing
HCV Hepatitis C virus
HIV Human Immunodeficiency Virus
HSV Herpes Simplex Virus
IATT Inter-agency Task Team on PMTCT
ICAP International Centre for AIDS Care and Treatment Programme
IDV Indinavir
IEC Information, Education and Communication
IF Infant Feeding

16
IFA Immunofluorescence Assay
IgG Immunoglobulin G
IHV-N Institute of Human Virology Nigeria
IMCI Integrated Management of Childhood Illnesses
INF-α Interferon-alpha
INH Isoniazid
IPT Isoniazid Preventive Therapy
LFT Liver Function Test
LIP Lymphoid Interstitial Pneumonitis
LMIS Logistic Management Information System
LPV/r Lopinavir/ritonavir
MTCT Mother-to-Child Transmission (of HIV)
MCH Maternal and Child Health
MRI Magnetic Resonance Imaging
MUAC Mid-Upper Arm Circumference
NACA National Agency for Control of AIDS
NAFDAC National Agency for Food and Drug Administration and Control
NASCP National AIDS/STIs Control Programme
NEPWHAN Network of People Living With HIV/AIDS in Nigeria
NFV Nelfinavir
NGO Non-Governmental Organisation
NNRTIs Non-Nucleoside Reverse Transcriptase Inhibitors
NPC National Population Commission
NRTIs Nucleoside Reverse Transcriptase Inhibitors
NSAID Non-steroidal Anti-Inflammatory Drugs
NtRTI Nucleotide Reverse transcriptase inhibitor
NVP Nevirapine
OIs Opportunistic Infections
OPV Oral Polio Vaccine
ORT Oral Rehydration Therapy
PABA People Affected By AIDS
PCR Polymerase Chain Reaction
PCM Paracetamol
PCP Pneumocystis jirovecii Pneumonia

17
PE Progressive Encephalopathy
PEP Post-Exposure Prophylaxis
PEPFAR President’s Emergency Plan for AIDS Relief
PI Protease Inhibitors
PITC Provider-Initiated Testing and Counselling
PSC Project Site-Coordinator
PMTCT Prevention of Mother-to-child Transmission of HIV
PLWHA People living with HIV and AIDS
RHSO Reproductive Health Services Outlets
RNA Ribonucleic Acid
RTV Ritonavir
SAPC State AIDS Programme Coordinators
SE Static Encephalopathy
SMR Sexual Maturity Rating
SMX Sulphamethoxasole
SQV Saquinavir
SR Sero-reverter
SSS Salt-Sugar Solution
STIs Sexually Transmitted Infections
T-20 Enfuvirtide
TB Tuberculosis
TDF Tenofovir
TF Task force
TFR Total Fertility Rate
TLC Total Lymphocyte Count
TMP Trimethoprim
TT Tetanus toxoid
TBA Traditional Birth Attendant
UNAIDS Joint United Nations Programme on HIV and AIDS
UNFPA United Nations Population Fund
UNICEF United Nations Children’s Fund
USAID United States Agency for International Development
VHW Village health worker/Voluntary health worker
VZV Varicella Zoster Virus

18
WHO World Health Organisation
ZDV Zidovudine

19
CHAPTER 1
INTRODUCTION
The World Health Organization (WHO) in 2006 estimated that 2.3 million children
are living with Human Immunodeficiency Virus (HIV) infection largely acquired
through mother to child transmission. It is estimated that over 1500 children are
infected with HIV every day all over the world. The Human Immunodeficiency Virus
now accounts for 6% of deaths in children younger than five years in Sub–Saharan
Africa. Recent data from WHO and Joint United Nations Programme on HIV and
AIDS (UNAIDS) indicate that only 40,000 of the more than 660,000 HIV positive
African children needing Anti retroviral therapy (ART) were receiving it in 2005.

Nigeria has the highest burden of MTCT rates and Paediatric HIV disease in the
world and the 2006 UNAIDS Report on the Global AIDS Epidemic indicated that
there are an estimated 240,000 children under 15 years old accounting for 14% of the
total African burden. The 2005 sentinel survey estimated that 74,520 new infections
would occur in children in 2006. The number of HIV positive children requiring ARV
was estimated to be 98,040, of which less than 5% actually received it.

From 1991 to 2005, the FMOH conducted biennial antenatal clinic sentinel surveys,
which showed HIV prevalence of 1.8% in 1992, 5.8% in 2001 and 4.4% in 2005
(Figure 1.1). The initial response to the epidemic concentrated efforts on the
establishment of adult ART and PMTCT programmes with minimal direct measures
to address the many challenges of HIV care for children. The development of these
guidelines is therefore, aimed at filling these gaps in the national response to the
epidemic of HIV and AIDS.

20
7

6 5.4
5.8 5
5 4.4
3.8
4 4.5
%
3

2
1.8
1

0
1992 1994 1996 1999 2001 2003 2005

Figure. 1.1: Median National HIV sero-prevalence trend

Objectives of the Guidelines

1. To provide standardized management protocols for children infected with or


exposed to HIV infection for all levels of health care delivery.
2. To provide guidance for monitoring and evaluation of Paediatric ARV services.
3. To provide guidance to advisory boards, programme managers and other policy
makers who are involved in the planning of Paediatric HIV care strategies.
4. To provide guidance on supportive care for children infected/affected by HIV
and AIDS.

Challenges of paediatric HIV and AIDS


Paediatric HIV and AIDS pose a number of challenges to the child, the
mother/caregivers, the family, the community and the nation as a whole. It is
important that these challenges are identified so that plans can be made to reduce the
overall impact of HIV and AIDS in children.

1. The challenges related to the prevention of mother to child transmission


In spite of the proven value of PMTCT services, a number of challenges negatively
impact the attainment of its goal including:

21
• The need to develop more effective, less expensive, and more feasible
interventions
• Making the PMTCT strategies globally accessible leaving out no mother or
child

2. Challenges of chronicity of the disease


• The provision of counselling and support services to enable the child, family
and caregivers cope with the disease and its complications
• The cost of care including repeated facility visits, adherence to treatment and
adverse drug reactions
• Emotional, cognitive and behavioural challenges which include coming to
terms with the diagnosis in the child and reactions of grief, guilt, sadness, and
anger.

22
3. Challenges to the health system
• Increased burden on already overstretched healthcare system as a result
increasing number of HIV infected children.
• Lack of access to and poor uptake of PMTCT services.
• Inadequate facilities for early infant diagnosis.
• Limited human resource capacity to manage paediatric HIV and AIDS
• Issues around infant feeding counselling.
• Lack of integration, poor linkages and weak referral system.
• Weak logistic management information system LMIS
• The challenge of regular monitoring and evaluation of the services.

4. Societal challenges
• Loss of productive age group
• Increasing number of orphans and vulnerable children
• Stigma, discrimination and cultural barriers to effective care and treatment

23
CHAPTER 2
VIROLOGY
2.1 Classifications and structure
The aetiological agents of AIDS have been identified as HIV-1 and HIV-2. These
viruses belong to the Lentivirus group of Retroviridae family. All the members of the
family contain an enzyme called reverse transcriptase that is used for the synthesis of
proviral DNA from the infecting viral RNA. This group of viruses is associated with
many diseases some of which may run a rapid course or have a long latency period.
Human immunodeficiency virus, like other retroviruses, has a positive single stranded
RNA. In the mature virus (Figure 2.1), the genome is diploid, with a 60-70s dimer of
two identical positive sense single-stranded RNA copies. Electron-microscopy studies
showed that HIV has a dense, cylindrical core whose structural elements are coded by
the gag gene for the protein that encloses the RNA genome.

The envelope is made of two glycoproteins Gp 120 and Gp 41 for HIV-1 and Gp 105
and Gp 36 for HIV-2. These trans-membrane proteins project out of the lipid barrier.
Antibodies to these two sets of proteins do not usually cross react and thus
differentiate serologic response to the two types of the virus.

The HIV pro-viral genome is approximately 10kb in length with an open reading
frame coding for the several viral proteins. The genome (Figure 2.2) is flanked at both
ends by long terminal repeat (LTR) sequences that contain regulatory segments for
HIV replication. It also comprises the gag, pol and env genes that code for the capsid
proteins, the viral enzymes and the internal and external envelope proteins
respectively. In addition to these major genes, an HIV genome has at least five other
genes Tat, Rev, Nef, Vif and Vpu/Vpx. Vpu is present in HIV-1 while Vpx is present in
HIV-2.

The envelope encloses the core proteins that in nature house the virus genome (RNA)
and the enzymes (reverse transcriptase, integrase and protease). The core is made up
of two proteins, p18 and p24.

24
The gag precursor p55 gives rise to five smaller proteins p25, p17, p9, p6 and p4 by
proteolytic cleavage. The pol precursor protein is cleaved into products consisting of
the reverse transcriptase (RT), the protease (PR), and the intergrase (IN) proteins.
The envelope precursor Gp160 is also split into two smaller glycoproteins, Gp120 and
Gp41.

Figure 2.1: Simplified schematic structure of HIV (Source: ANECCA Handbook on


Pædiatric AIDS in Africa 2006)

Figure 2.2: Genomic structure of a typical HIV-1 (Source: AIDS in Nigeria, 2006)

The Gp120 forms the external surface (SU) envelope protein and the Gp41, the
transmembrane (TM) protein. The Gp120 contains the binding site for the cellular
receptor and major neutralizing domain.

25
2.2 Variability of HIV isolates
HIV exhibits marked genetic diversity among different isolates. This heterogeneity is
distributed throughout the viral genome and most of it is located in the env gene.
Based on this variability HIV has been classified into types 1 and 2. HIV-1 has a
global distribution while HIV-2 is limited to West Africa. Nevertheless, HIV-1 is still
the predominant type in this sub-region. The 2 sub-types of the virus also vary in their
biological characteristics. The rate of transmission is higher and progression to
disease is faster in HIV-1 than in HIV-2.

HIV-1 is classified into subtypes using the nucleotide sequence of the gag, pol and
env genes. Subtypes of HIV-1 using the env gene have been based mainly on the
third variable region (V3 loop) of the Gp120, known to be important in viral cell type
tropism, virus cell-fusion and cytopathology. Based on the nucleotide of the V3 loop
of the Gp120, HIV-1 has been classified into three major groups, the group M
(major), N (non-M, non-O) and group O (Outlier). The group M virus has been
further classified into at least 10 different subtypes (A to J). In addition,
recombination of the virus subtypes is a well known phenomenon and many
recombinant forms including the A/G which is the most predominant subtype in West
Africa have been identified. HIV-2 is classified into 5 subtypes, A-E and recombinant
forms have not been identified. In Nigeria, the A/G and the G subtypes are
predominant.

Co-infection or super-infection of an individual by HIV-1 and HIV-2 has been well


documented. Infection with different HIV-1 and HIV-2 subtypes has also been
reported.

2.3 Cellular receptors


The primary receptor for HIV is the CD4+ molecule on the T-helper cells of humans.
Recent advances in genetics of infectious diseases have shown that human genetic
variation might influence susceptibility to pathogenic organisms. Variation in CD4+
receptive molecule on T-cells surface may influence the ability of HIV to bind and
eventually penetrate the target cell. In addition, attachment to and fusion with the
target cells is determined not only by its binding with CD4+ molecules, but also other
secondary binding sites known as β-chemokines such as CCR5 and CXCR4.

26
Individuals who are homozygous for a deletion in the CCR5 or CXCR4 gene are less
frequently infected with HIV. Those who are heterozygous for the same mutation
become infected but can be protected against rapid progression to disease compared
with infected individuals homozygous for the normal CCR5 or CXCR4 gene.

2.4 Replication
Replication of the virus particle begins with attachment of Gp120 to the CD4+ on the
surface of a target cell. Following the Gp120-CD4+ binding, a structural change
allows for the interaction of the V3 loop region in the Gp120 with a chemokine
receptor, including CCR5 and CXCR4. The reaction with the co-receptor results in
another conformational change in the viral surface glycoprotein, which exposes a
fusion domain contained within the envelope trans-membrane glycoprotein. Exposure
of the fusion domain results in the insertion of the Gp41 into the cellular membrane.
Subsequent to the fusion event, the viral core is released into the cytoplasm of the host
cell. Once in the cytoplasm, the viral RNA genome is uncoated and reverse
transcribed by the virally encoded RT enzyme to generate a double-stranded viral
DNA pre-integration complex.

The double stranded DNA is then transported into the host cell nucleus where it
becomes integrated into the host cell chromosome with the aid of integrase. It then
resides as a provirus and may remain in a ‘latent’ state for many years or can begin
the production of new viral RNA. On activation, the host cell enzyme RNA,
polymerase II will transcribe the proviral DNA into messenger RNA (mRNA).

The mRNA is then translated into viral proteins that undergo extensive post-
translational modifications. The viral RNA becomes the genetic material for the next
generation of viruses. Viral RNA and viral proteins assemble at the cell membrane.
After proper assembly and processing, new infectious virus particles are released by
budding from the cell membrane.

27
Figure 2.3: HIV replication cycle (Source: ANECCA Handbook on Pædiatric AIDS in Africa
2006)

2.5 Natural history in children below 6 years


Clinical Course of Illness
There are critical differences between the disease progression in children and in
adults. Stemming largely from the lower efficiency of a child’s immature (but
developing) immune system, these differences result in much more rapid disease
progression and a much shorter duration for each stage. Perinatally acquired HIV
infection demonstrates defined modes of expression of disease.

At birth, viral load is usually very low and then slowly rises within the first 2 months
of life to values above 100,000 copies/ml and slowly decreases only after the age of 4-
5 years. These viral dynamics are significantly different from the rapid increase and
decrease of the viral load seen in untreated children older than 6 years and adults
within a few months following the acute HIV infection (Figure 2.4).

28
Figure 2.4: Dynamics of virus and CD4+ levels over the course of untreated HIV
infection

In children, the higher viral load is associated with the somatic growth of the
lymphatic system and the inability of their immature immune system to mount an
HIV-specific response. When assessing the immune system in infants and children, it
is very important to compare the child’s CD4+ T-cell count with the age-appropriate
values (e.g. the mean CD4+ T-cell count for a 6-month-old baby is 3,000 cells/µl).
Lymphocyte counts are very high in infancy and decline to adult levels around 6 years
of age.

A higher mortality in HIV-infected children may result from inter-current infections,


malnutrition, and lack of access to primary HIV care including delayed definitive
diagnosis. With no interventions, the majority of perinatally HIV-infected children
develop HIV-related symptoms by 6 months of age. There is limited data on clinical
and biological indicators of disease progression in HIV-infected children in Nigeria.

29
2.6 Natural history of HIV infection in children ≥ 6 years
The course of HIV infection varies within a population. Nonetheless, a typical
infection can be divided into three stages: primary infection, asymptomatic infection,
and symptomatic infection including AIDS. Following primary HIV infection, the
CD4+ cell count decreases and the HIV RNA rises significantly. With sufficient
exposure to viral antigens, cytotoxic T-lymphocyte responses are generated and the
HIV viral load typically declines to an equilibrium known as a virologic “set-point,”
within 6 to 12 months of infection. Once this viral set-point is reached, the CD4+ cell
count may rebound again marginally, although it does not often return to baseline
values. Concurrent with these events are clinical manifestations of acute HIV
infection in 30% to 60% of individuals.

About half of newly infected individuals experience flu-like symptoms; the remainder
are asymptomatic. Once infected, adults experience an asymptomatic clinical latency
that lasts 2 to 10 years, during which HIV is produced and removed by the immune
system, and CD4+ T cells are killed and replaced. This latency period is considerably
shorter in children. During this asymptomatic period, the number of infected
circulating CD4+ cells and free virions is relatively low. Moreover, the hematopoietic
system is able to replace most T cells that are destroyed, thus keeping the CD4+ cell
counts in the normal range for adults and children >5 years (636-977 cells/µl).

Later in infection, replicating viruses disrupt the follicular dendritic cells’architecture,


and more infected T cells appear in the circulation. Viruses are no longer retained in
the lymph nodes; thus, the circulating levels of free virus increase. Eventually, the
circulating CD4+ T cell levels drops to less than 500 cells/µl and opportunistic
infections may occasionally occur. During the later stage of infection, the CD4+ cell
count declines below 200/µl, a level at which the infected individual is deemed to
have severe immune suppression.

A number of opportunistic infections, including recurrent oral candidiasis and


tuberculosis are common during the early symptomatic phase of AIDS. As the CD4+
cell count declines to an even lower level, additional life-threatening opportunistic
infections such as herpes zoster, amoebiasis, and dermatomycoses may occur with
increasing frequency and severity. In the later stages of symptomatic HIV infection,

30
the viral load levels rise again. Quantitative PCR methods (viral load assays),
demonstrate:
• Continuous replication of HIV occurs in nearly all infected individuals,
although the rates of virus production vary by as much as 70-fold in different
individuals;
• The average half-life of an HIV infected cell in vivo is 2.1 days. Recent
reports have suggested an even faster turnover of plasma virus of 28 to 110 per
minute;
• Up to 109–1010 HIV particles are produced each day; and an average of 2 x109
CD4+ cells are produced each day.

Quantifying the viral load is currently the most direct measurement of the HIV
disease process. It is used to assess the risk of disease progression and the response to
antiretroviral therapy (ART). As the disease progresses, CD4+ cell count declines but
may rebound if therapy is efficacious; this parameter alone is an incomplete marker
for clinical assessment of a patient. Nevertheless, in resource poor settings, the CD4+
cell count is a more affordable and hence more practical yardstick for monitoring
disease progression and ART efficacy.

Fig. 2.5: Changes in viral load over time and magnitude of virus-specific
cytotoxic T lymphocyte (CTL) activity in untreated adult and paediatric HIV
infection (Source: Andrew Prendergast, et al. International perspectives, progress,
and future challenges of paediatric HIV infection. Lancet 2007; 370: 68–80).

31
Perinatally infected children fit into one of three categories:
• Category 1: Rapid progressors develop signs and symptoms of HIV and AIDS
and die by age 1 year. These children are likely to have acquired the infection
in utero or during the early perinatal period (about 25–30%)
• Category 2: Children develop symptoms early in life, followed by rapid
deterioration and death by age 3 to 5 years (about 50–60%)
• Category 3: Long-term survivors live beyond age 8 years (about 5–25%)

2.7 Factors predicting prognosis


Predictors of prognosis are derived mainly from studies performed in industrialized
countries; however, these predictors are also useful in the African context. HIV RNA
and CD4 percent provide complementary and independent information about the
prognosis for HIV-infected children. The two markers together at baseline and with
changes over time provide a more accurate prognosis.

Table 2.1: Factors predicting disease progression in infants

Infant factors Maternal factors


• Infecting viral dose • Maternal viral load at time of
• HIV infection before 4 months of life delivery
• Infant peak viraemia • Maternal CD4+ cell count (<200
• Low CD4+ count and percent cells/µl)
• Viral type and subtypes • Rapidly progressive maternal disease
• Rapid decline in CD4+ count • Maternal death, which is associated
• Clinical AIDS with a 2- to 5-fold increase in infant

• p24 antigenaemia mortality when compared to infants


born to mothers who survive

32
CHAPTER 3
DIAGNOSIS OF HIV AND AIDS IN CHILDREN

Introduction
Clinical signs and symptoms are useful parameters in making a diagnosis of HIV
infection, but in children these features overlap with those of other common
childhood diseases. The definitive diagnosis of HIV infection in children at any age
requires diagnostic test that confirms presence of human immunodeficiency virus.

3.1 Clinical presentation


HIV infection is associated with an increased frequency of common childhood
infections. These tend to be recurrent, persistent, severe and sometimes life
threatening. As the immune system gets destroyed, opportunistic infections become
very common. Majority of HIV-infected children develop symptoms and signs of
severe immuno-suppression in the first year of life and frequently die from common
childhood infections before their HIV status is determined. Consequently, HIV and
AIDS have increased infant and under-five mortality in many developing countries.

HIV-infected children usually have flu-like symptoms shortly after infection. These
resolve unnoticed or present as the common illnesses in the environment. Thus, the
presentations range from the symptoms and signs of the common childhood illnesses
to those highly specific to the HIV infection.

The early features are non-specific and may include fever, diarrhoea, weight loss,
failure to thrive, and cough. As the illness progresses, the child presents with
additional features that indicate severe immune suppression. These include those of
opportunistic infections, recurrent and more severe forms of the common illnesses in
the environment and malignancies. These presentations are discussed below.

3.1.1 General manifestations


a. Fever
Fever (an axillary temperature of 37.5oC or higher) is an important symptom in
children. However, in the HIV-infected child, in addition to the usual causes of fever,

33
the virus itself, malignancies and ARVs are known causative factors. Fevers in HIV-
infected children tend to be persistent (lasting 7 days or more) or recurrent (see Table
3.3: Clinical staging). The evaluation of a child with fever should be carried out as in
the HIV uninfected child but attention should be paid to features of opportunistic
infections. The assessment involves taking a detailed history and doing a full general
examination to identify probable causes. Investigations such as full blood count
(FBC) and cultures of specimens (such as cerebrospinal fluid (CSF), urine, blood or
other body fluids/ tissues) to identify possible causes should be carried out. Blood
film should also be examined for malaria parasites.

b. Persistent generalised lymphadenopathy


Persistent generalised lymphadenopathy is one of the most common early clinical
presentations of HIV-infected children. It may also be associated with parotid
enlargement and or hepatosplenomegaly. A biopsy may show non-specific
inflammation of the nodes. Other causes include disseminated TB, acute
toxoplasmosis, rubella, CMV, herpes, leukaemia, Kaposi’s sarcoma (KS) and
syphilis.

3.1.2 Common infections and illnesses


a. Respiratory infections
Respiratory infections are common in children and contribute to about 30% under-
five deaths. The infections can affect the upper or lower respiratory tracts. The signs
and symptoms include fever, cough, fast or difficult breathing, rhinitis, ear pain or
discharge and sore throat. The common causes of the infection, especially
pneumonias, are viruses such as Respiratory Syncytial virus, bacteria, such as Strept.
pneumoniae, H. influenzae and Staph. aureus. These pneumonias tend to be acute
and recurrent. In the early phase of the HIV infection, the child is still immuno-
competent and responds to these infections as the uninfected child. However, as the
immune system becomes suppressed, the child’s susceptibility to opportunistic
infections increases. At this stage, the child no longer responds appropriately to the
infection and may be overwhelmed by the pneumonia with more persistent symptoms
and signs and the complications become more frequent. Other respiratory infections
include recurrent episodes of mastoiditis and pharyngotonsilitis (sore throat).

34
The assessment of the child involves taking a detailed history and carrying out a full
clinical examination with emphasis on the respiratory system. Health workers at the
first level of care can use the IMCI Guidelines to manage the child. Investigations
include full blood count (FBC), chest radiographs, cultures of sputum, pleural fluid or
blood to isolate probable aetiologic agents.

Otitis Media
Ear infection is one of the most common infections in HIV-infected children. Acute
otitis media refers to ear infections that have lasted for less than 14 days. Acute
suppurative otitis media is more common in infected children in the first year of life.
By age 3 years, most HIV-infected children will have had one or more episodes of
acute otitis media. Signs and symptoms are similar to those in other children and
include ear pain, pulling on the ears, excessive crying, ear discharge, and irritability.
At otoscopy the eardrum is hyperaemic, bulging, immobile and may be perforated.

Chronic suppurative otitis media is painless ear discharge lasting >14 days. It is more
frequent in HIV-infected children, its presence particularly with recurrence should
prompt the health worker to screen for HIV infection.

b. Malaria
Malaria is a major cause of morbidity and mortality in children in Nigeria. Some
reports have shown that infants born to HIV-infected women are more likely to suffer
from congenital malaria than children born to uninfected women. Likewise, an
increased frequency of malaria has been noted in HIV-infected children. Additionally
HIV-infected children are more likely to be anaemic during an episode of malaria
compared to uninfected children. There is need for research in these areas to generate
local data.

Clinical presentation is similar to uninfected children and treatment recommendations


should follow the National Malaria Guidelines.

c. Malnutrition
Malnutrition is very common among HIV-infected children due to the following
reasons:

35
• Decreased food intake because of anorexia associated with illness, mouth
ulcers and oral thrush
• Increased nutrient loss resulting from malabsorption and diarrhea
• Increased catabolism due to co-infections, OIs and the HIV infection itself

The effects of malnutrition are compounded by the high burden and recurring
infections and infestations in HIV-infected children. In addition, HIV-positive
mothers have higher rates of low-birth-weight babies and premature birth, which are
risk factors for malnutrition. Characteristics of HIV-infected children associated with
malnutrition include:
• Micronutrient deficiencies (e.g. low serum levels of zinc, selenium,
vitamins, A, E, B6, B12 and C) lead to reduced immunity which predisposes
them to more infections and worsening nutritional status
• Decrease in linear growth and weight which become apparent as early as 3
months of age.

The clinical presentation of diseases in HIV-infected children is similar to that of


HIV-negative children. However, marasmus is more common than kwashiorkor
among HIV-infected children.

d. Tuberculosis (TB)
HIV infection increases a child’s susceptibility to infection with Mycobacterium
tuberculosis. The presence of TB may allow HIV to multiply more quickly resulting
in more rapid progression of the disease. Pulmonary presentation is the most common
form of TB in HIV-infected children. M. tuberculosis infection is one of the major
causes of morbidity in the HIV- infected child. With increasing spread of HIV
infection, there is a corresponding increase in the incidence of tuberculosis as well as
an increase in multi-drug resistant strains of M. tuberculosis. The presence of multi-
drug and extensively resistant M. tuberculosis has added considerable challenge to the
treatment and control of TB. The symptoms and signs are similar to those in non-
HIV-infected children but extra-pulmonary manifestations such as meningitis,
disseminated or miliary forms are more common in HIV-infected children. The
confirmation of the diagnosis of tuberculosis in children is difficult.

36
Investigations to assist in the diagnosis of tuberculosis include:
• Mantoux test: a result of >5mm should be considered positive but sometimes
because of anergy, the test may be falsely negative
• Radiographs of the chest and other relevant areas of the body e.g. spine: most
changes are similar to those in the non HIV-infected children and chest x-rays
may be normal. However, cavitations are particularly common in the HIV-
infected child
• Microscopy and cultures of relevant specimens: these may detect acid-fast
bacilli and help isolate the organism
• Histologic examination of tissues such as lymph nodes will show tuberculous
granulomas
• FBC and ESR are useful ancillary investigations
• PCR testing for TB is useful in confirming the diagnosis. However it is
currently not widely available in Nigeria.

e. Measles
Measles is one of the major causes of morbidity and mortality and is a severe illness
in children with HIV infection, particularly those with advanced immunodeficiency. It
may occur in early infancy in HIV-infected children because of inadequate transfer of
maternal antibodies. Infection may occur despite history of immunisation. Severe
cases can occur without the typical rash and may be complicated by pneumonia or
encephalitis. HIV-infected children with measles have a high case fatality and should
be treated in hospital.

3.1.3 Gastrointestinal Manifestations


The common gastrointestinal manifestations of HIV infection are nausea, vomiting,
diarrhoea and wasting.

a. Nausea and vomiting


These are common complaints in the HIV-infected child. The causes are many and
may include inflammatory lesions of the gastrointestinal tract, meningo-encephalitis,
malignancies and metabolic abnormalities. Medications such as ARVs, prophylactic
and anti-cancer agents may also cause nausea and vomiting. A detailed history should

37
be obtained and a full physical examination carried out to determine the causes in
each case.

b. Diarrhoea
Diarrhoea is a common presentation in HIV-infected children. Aetiological factors
include HIV infection itself, other infections of the gut, osmotic diarrhoea,
malabsorption syndrome, and lactase deficiency. The diarrhoea may be acute,
persistent, or chronic and is often recurrent. The assessment of the child involves a
detailed history and physical examination. Identification of the cause of the diarrhoea
is often difficult but stool analysis and culture may be helpful.

c. Parotid enlargement
Parotid gland enlargement, usually bilateral, is one of the most specific signs of HIV
infection in children. It is usually not tender and is commonly found in older children
who are slow progressors. It may be associated with hepato-splenomegaly and LIP.
When exceptionally large, it may be disfiguring and lead to emotional distress.
Intermittently the glands may enlarge and regress over several months, and may
become tender from bacterial super-infection.

d. Viral hepatitis
Hepatitis B and C infections are common in HIV-infected children. Infection occurs
by the same routes as in the non HIV-infected child. It may be asymptomatic or
present with fever, nausea, abdominal pain and jaundice. The patient may present
with complications of the illness such as bleeding tendencies, seizures and coma
because of liver failure. A detailed history and examination of the child should be
carried out. Investigations include HBV and HCV antigen and antibody levels, LFTs,
FBC, abdominal ultrasound and other tests as indicated.

3.1.4 Oral and cutaneous manifestations of HIV and AIDS


a. Herpes simplex virus (HSV) infection
HSV-1 and HSV-2 occur 10-35 times more commonly in HIV-infected children and
adults than in non- infected persons. The presence of herpetic lesion for >1 month is
an indicator of AIDS. HSV infection causes painful cold sores around the mouth, the
rectal and genital areas. The presentations of the infection in HIV-infected children

38
though similar to those in the non-infected, are more severe. Chronic progressive
herpetic lesions may also be found. Recurrences of the lesions are very common.
Diagnosis is mainly clinical but viral cultures can also be done.

b. Varicella-zoster virus (VZV) infection


This is a herpes virus that causes varicella (chickenpox) and zoster (shingles) in
children and adolescents. Past history of chickenpox increases the risk of shingles.
Patients with severe immunodeficiency have severe manifestations of the infection
with dissemination to the lung, liver, brain or pancreas. Some patients have a
syndrome of chronic VZV infection. Symptoms of the infection include the presence
of small, painful blisters that follow a dermatomal distribution. Complications include
severe painful ulcerations, post-herpetic neuralgia and disseminated disease.
Diagnosis is mainly clinical but viral cultures can also be done. Confirmation of
diagnosis is by the use of Tzanck smear.

c. Molluscum contagiosum
The infection presents as painless, pale, umbilicated nodules measuring 3-5 mm. They
may occur anywhere on the body but are most commonly seen on the face. The major
effect is cosmetic. In adolescents, it occurs when the CD4+ cell count is <200 cells/µl.
When the count is less than 50 cells/µl, the giant forms of the lesions are seen. There
is a high rate of recurrence.

d. Bacterial skin infections


Bacterial skin infections often found in HIV-infected children include folliculitis,
cellulitis, skin abscesses, and paronychia. These infections tend to be recurrent in the
HIV-infected child. The commonest organism isolated is Staph. aureus.

e. Fungal infections
Candidiasis and dermatophytosis are common fungal infections found in HIV-
infected children.
i. Candidiasis
Candida albicans is the most common cause of fungal infection in HIV-infected
children. It can present with oral, oesophageal, skin, perineal and vaginal lesions
with oral thrush being the commonest. Oral thrush may be the only indication of

39
HIV infection in a child, recurrence or poor response to therapy is highly
suggestive of HIV infection. The patient presents with whitish or yellowish
plaques on the oro-pharyngeal mucosa. When there is oesophageal infection,
there may be inability to swallow or retro-sternal chest pain and refusal to feed.
Cutaneous candidiasis is commonly found in the nappy areas and skin folds.
Candida septicaemia may occur in severely ill patients and those on long-term
antibiotics or carrying an indwelling catheter. Diarrhoea may be a
gastrointestinal manifestation. Diagnosis is mainly clinical and isolation of the
organism from relevant specimens can be done.

ii. Dermatophytosis
Dermatophyte infections such as tinea corporis, capitis or cruris occur
commonly in HIV-infected children. They present characteristically as flat
scaling lesions with raised borders. The presence of tinea unguim may be
suggestive of immune suppression.

f. Aphthous ulcers
These are small painful blisters on the tongue, mucous membranes of the mouth,
tonsils, oro-pharynx or gastrointestinal tract. The diagnosis of aphthous ulcer is one of
exclusion when other infectious and non-infectious causes of mouth ulcers have been
excluded. Some medications such as AZT, and foscarnet can cause aphthous ulcers.
Recurrence is however very common.

g. Seborrhoeic dermatitis
This occurs more severely in HIV-infected children. It is characterised by thick
yellow scales occurring on the scalp but may also be seen on the face or nappy area.
In older children (>12 months) the naso-labial folds and the skin behind the ear and
eyebrows may also be affected.

h. Scabies
This is characterised by papular pruritic lesions found commonly in the webs of the
fingers and toes, folds of the wrist, gluteal region, ante-cubital areas and axillae. The
lesions may affect the soles and palms. In severely immuno-suppressed individuals
the severe form, Norwegian scabies, occurs. This is characterised by generalised

40
scaling and enlarged crusted plaques. Scraping of the sites viewed under the
microscope will reveal the mites or their eggs or faeces.

i. Oral hairy leukoplakia


While this affects about one third of HIV-infected adults, it is less common in
children. It is related to Epstein- Barr virus infection and occurs when the immune
suppression is severe. The lesions appear whitish or greyish along the margins of the
tongue. They often have vertical corrugations and when the mucosa is dry, they
appear hairy.

j. Peri-odontal disease
This occurs commonly in children with HIV infection and the manifestations range
from mild redness around the gum to necrotising ulcerative peri-odontitis, severe
ulceration with destruction of the gum. The ulcerative peri-odontitis can result in
extensive loss of soft tissue and teeth. Severe lesions cause pain and poor oral intake.
Poor oral hygiene is a common problem among HIV-infected children and it needs
special attention. Diagnosis is clinical.

3.1.5 Haematologic manifestations


The three cell lines in the blood can be suppressed in HIV infection resulting in
anaemia, neutropaenia or thrombocytopaenia, occurring singly or in combination. The
causes include drugs and infections by the HIV virus and other organisms.

a. Anaemia
The anaemia in HIV infection has multiple origins, which include the following:
• Reduced production of erythrocytes caused by HIV infection, other infections
(CMV, Parvovirus B19, tuberculosis), malignancies (lymphoma and Kaposi’s
sarcoma) and drugs (AZT, d4T, sulphonamides and dapsone)
• Destruction of erythrocytes caused by the haemo-phagocytic syndrome,
disseminated intravascular coagulation (DIC) and drugs
• Ineffective erythropoeisis due to deficiency of erythropoeitic factors - iron,
folic acid and vitamin B12. These result from inadequate intake, poor
intestinal absorption and/or infections in the gastrointestinal tract.

41
b. Neutropenia
This is defined as an absolute neutrophil count of less than 1000/mm3 for children
aged 2 weeks to 1 year and 1500/mm3 for children aged over 12 months. When the
absolute neutrophil count is below 500/mm3, opportunistic infections occur. The
neutropaenia in HIV-infected children may result from decreased levels of factors that
stimulate the production of white blood cells G-CSF. Decreases in the levels of white
blood cell growth factors lead to reduction in the numbers of progenitor cells in the
bone marrow. This leads to a decrease in the number of granulocytes and monocytes.
There is also a decrease in the level of G-CSF in the blood. This is associated with
decreased numbers of neutrophils. Neutropaenia can also be caused by antiretroviral,
antifungal, anti-neoplastic and PCP prophylactic drugs. The neutropaenic child may
be asymptomatic or may present with fever, skin ulcerations or eruptions, chest
infections, stomatitis, dysphagia, and peri-rectal pain or fissures.

c. Thrombocytopaenia
This is said to be present when the platelet count is less than 100,000/mm3. HIV may
cause thrombocytopenia but the cause is unknown in most patients. The
thrombocytopaenic child presents with easy bruising, petechiae, purpura, epistaxis,
gingival bleeding, haematuria and haematochezia.

3.1.6 Neuro-developmental manifestations of HIV infection


The nervous system is often involved in HIV infection with manifestations ranging
from mild delays in developmental milestones to severe progressive encephalopathy.
The causes of these nervous system manifestations include HIV infection (direct viral
invasion of the CNS), complications related to immune suppression, chemical
mediators and the neurotoxic effects of ARV therapy. The peripheral nervous system
manifestations are multi-focal and may be due to the attack of the virus on the
peripheral nervous tissue. Children who are severely immuno-compromised may have
opportunistic infections of the nervous system. Malignancies of the CNS such as
lymphomas and leiomyosarcomas may also contribute to the nervous system
manifestations. These manifestations are described below (Table 3.1).

42
Table 3.1 Neurologic manifestations of paediatric HIV infection
Abnormality Clinical findings Diagnostic studies
Developmental Delay or loss of developmental and Neuro-developmental testing,
delay language milestones and microcephaly speech and language testing,
head circumference
measurements reveal delays for
age.
Progressive Fine and gross motor deficits (usually CT/MRI: brain atrophy, white
encephalopathy symmetrical), gait disturbance, hyper-or matter abnormalities
(PE) hypotonia, spasticity, inability to bear
weight or ambulate, neuro-developmental
delay, microcephaly, confusional states

Static Fixed non-progressive or static motor CT/MRI: loss of brain tissue


encephalopathy deficits, developmental delay,
(SE) microcephaly

Seizures Generalized or focal seizure activity EEG: abnormal patterns


CT/MRI: findings depend on
aetiology
E &U estimation
CSF: may be positive for
pathogens, if infectious in
aetiology
Myopathy Muscle weakness, myalgia, loss of muscle EMG: irritative myopathy
bulk Muscle biopsy: inflammation
and degeneration

Myelopathy Gait disturbances, lower extremity MRI: normal or inconclusive


weakness and stiffness, urinary and faecal
incontinence, spasticity, Babinski sign,
sensory abnormalities

Focal cerebral Headache, nausea, vomiting, gait CT/MRI: enhancing lesions


mass lesion instability, motor deficits, visual changes

43
Table 3.1……cont
Abnormality Clinical findings Diagnostic studies
Opportunistic Headache, nausea, vomiting, confusion, CSF: positive for pathogens, if
infections coma, malaise, fever, behaviour changes, infectious in aetiology
seizure activity Serology: positive for aetiologic
pathogens
CT/MRI: multiple enhancing
lesions (toxoplamosis); peri-
ventricular and meningeal
abnormalities (CMV)
Peripheral Distal symmetrical neuropathy, distal EMG: Distal axonopathy
neuropathy numbness, pain, paraesthesias, decreased
ankle reflexes, glove and stocking sensory
loss, pseudoparalysis.

Inflammatory demyelinating EMG: demyelination


polyneuropathy: progressive weakness,
paraesthesias, areflexia, mild sensory loss.

Progressive poly-radiculopathy: lower


extremity weakness, paraesthesias, EMG: polyradiculopathy.
urinary incontinence and retention, Serum: Increased creatinine
diminished reflexes kinase

3.1.7 HIV-associated malignancies


The incidence of malignancies in HIV-infected children is not as high as in HIV-
infected adults. The common malignancies seen in HIV-infected children are non-
Hodgkin’s lymphomas and Kaposi’s sarcoma. There has also been an increase in
other types of malignancies in some African countries- retinoblastoma,
rhabdomyosarcoma and nasopharyngeal carcinoma among HIV-infected children

3.2 Approach to diagnosis


A rational approach to diagnosis of paediatric HIV infection requires health workers
to have a high index of suspicion, some knowledge and communication skills to
enable them discuss and offer HIV testing to children and their parents.

44
Diagnosis may be:
• Clinical (based on signs and symptoms), or
• Clinical supported by laboratory findings

HIV and AIDS should be suspected among children with suggestive clinical signs or
HIV-associated conditions (see Table 3.2). Health workers should also evaluate
children born to HIV-infected mothers, those who are sexually assaulted and those
exposed to potentially infectious body fluids. If HIV infection is confirmed, the exact
clinical stage of disease should be determined using the WHO staging system (Table
3.3).

45
Table 3.2 Clinical signs or conditions in a child that may suggest HIV infection

Specificity for Conditions


HIV infection
Very Specific to • Pneumocystis pneumonia
HIV infection • Oesophageal candidiasis
• Extrapulmonary cryptococcosis
• Invasive salmonella infection
• Lymphoid interstitial pneumonitis
• Herpes Zoster (shingles) with multi-dermatomal involvement
• Kaposi’s Sarcoma
• Lymphoma
• Progressive multi-focal leuco-encephalopathy
Conditions • Severe bacterial infections especially if recurrent
common in HIV • Persistent or recurrent oral thrush
infected and • Bilateral painless parotid enlargement
uncommon in • Generalized persistent non-inguinal lymphadenopathy
uninfected • Hepato-splenomegaly (in non-malaria endemic areas)
children • Persistent and/or recurrent fever
• Neurologic dysfunction
• Herpes Zoster, single dermatome
• Persistent generalized dermatitis unresponsive to treatment
Conditions • Chronic recurrent otitis media with ear discharge
common in HIV • Persistent or recurrent diarrhea
infected children • Severe pneumonia
but also common • Tuberculosis
in uninfected • Bronchiectasis
• Failure to thrive
• Marasmus

46
Table 3.3: WHO Staging system for HIV infection and disease in infants,
children and adolescents
Clinical Stage 1 (Asymptomatic)
• Asymptomatic
• Persistent Generalized Lymphadenopathy
Clinical Stage 2 (Mild)
• Unexplained persistent hepatosplenomegaly
• Papular pruritic eruptions
• Extensive wart virus infection
• Extensive molluscum contagiosum
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Linear gingival erythema
• Herpes zoster
• Recurrent or chronic upper respiratory tract infection (otitis media, otorrhoea,
sinusitis, tonsillitis)
• Fungal nail infections
Clinical Stage 3 (Advanced)
• Unexplained moderate malnutrition not responding to standard therapy
• Unexplained persistent diarrhoea (14 days or more)
• Unexplained persistent fever (>37.50 C, intermittent/ constant, longer than 1
month)
• Persistent oral candidiasis (after 1st 6 weeks of life)
• Oral hairy leukoplakia
• Acute necrotizing ulcerative gingivitis/periodontitis
• Lymph node TB
• Pulmonary TB
• Severe recurrent bacterial pneumonia
• Symptomatic lymphoid interstitial pneumonitis
• Chronic HIV-associated lung disease including bronchiectasis
• Unexplained anaemia (<8.0 g/dl), neutropenia (<0.5 x 109/l3)
• Chronic thrombocytopenia (<50 x 109/l3)

47
Clinical Stage 4 (Severe)
• Unexplained severe wasting, stunting or severe malnutrition not responding to
standard therapy
• Pneumocystis pneumonia
• Recurrent severe bacterial infections (e.g. empyema, pyomyositis, bone or
joint infection but excluding pneumonia)
• Chronic Herpes simplex infection (oro-labial or cutaneous of >1 month, or
visceral at any site)
• Extra-pulmonary TB
• Kaposi’s sarcoma
• Oesophageal candidiasis (or candida of trachea, bronchi or lungs)
• Central nervous system toxoplasmosis (after the neonatal period)
• HIV encephalopathy
• CMV infection; retinitis or infection affecting another organ with onset >1
month)
• Extra-pulmonary cryptococcosis (including meningitis)
• Disseminated endemic mycosis (extra-pulmonary histoplasmosis,
coccidiomycosis)
• Chronic cryptosporidiosis (with diarrhoea)
• Chronic isosporidiasis
• Disseminated non-tuberculous mycobacterial infection
• Cerebral or B-cell non-Hodgkin lymphoma
• Progressive multifocal leukoencephalopathy
• HIV-associated cardiomyopathy or nephropathy
• HIV-associated recto-vaginal fistula

3.3 Laboratory diagnosis of HIV infection


There are 2 broad categories of tests for diagnosis of HIV infection: detection of
antibodies or of the virus/viral components in a patient’s blood sample. The choice of
which method to use is determined by age, time of exposure and cost.

48
3.3.1 Antibody tests

• HIV rapid testing: these are relatively inexpensive and easy to perform and
should be used according to the National Testing Algorithm.
• HIV Enzyme-linked Immunosorbent Assays (ELISA): Although requires
more equipment, time and technical skills, it is more sensitive than rapid tests.
• Western Blot: This is the gold standard test for confirmation of HIV infection,
but is expensive and subject to indeterminate results.

3.3.2 Detection of virus/viral components


• DNA PCR; this is a very sensitive test useful especially for infant diagnosis
• RNA PCR (plasma viral load): is especially useful for monitoring disease
progression and response to treatment
• p24 antigen detection by ELISA: This is a very specific test that detects the
core viral antigen produced in the early phase of infection. It is useful for
detecting infection in the window period, however, a negative result does not
rule out infection
• Isolation of HIV by culture: This technique is highly sensitive and specific.
However, it is time consuming (4 weeks), very expensive and recommended
mainly as a research tool.

3.4 Diagnosis in children


a. Age < 18 months
• Children less than 18 months of age born to HIV infected mothers may
have circulating maternal antibodies and a positive antibody test may be
from the child and/or the mother. Therefore virus/viral component
detection test such as DNA PCR is the test of choice.
• The optimal time for DNA detection test in non-breastfeeding children is
2-3 months of life and 3 months after cessation of breastfeeding.
• At the end of 18 months of life, an antibody test should be performed
irrespective of whether a child received breastmilk or replacement feeds.

49
b. Age >18 months
• Antibody detection is very useful and reliable for children >18 months
except during window period (4-6 weeks post-exposure) where antibodies
may not be present at a detectable level.
• Repeat of antibody testing 3 months later is recommended if window
period is suspected.
• On rare occasions a patient with AIDS may test p24 antigen and/or
antibody negative because of the formation of complexes between the viral
antigens and the corresponding antibodies.
• Methods such as DNA/RNA PCR could be used to resolve false negative
results.
The algorithm below (Fig. 3.1) indicates an approach to the laboratory evaluation,
diagnosis and follow up of exposed or infected infants.

50
Paediatric Program:
ƒ Emergency Ward PMTCT Program*
ƒ Inpatient Ward
ƒ Outpatient Clinic

HIV Exposed Child


Children <18m with signs and Î Refer mother to care &
symptoms suggesting HIV treatment or VCT if status
was previously unknown
Î Start CTX
Routine RT Î If clinically indicated
(WHO clinical staging) refer
RT–ve RT+ve
child to ART clinic
Non-HIV HIV
Î Test infant for HIV
Exposed Exposed BF=breastfed
If signs &
RT=Rapid Test
symptoms are Child 9-18m Child < 9m
suggestive of HIV RT first.
send PCR. If no, Send PCR** Send PCR
evaluate other
causes.
Has the child
POS NEG BF in the last
6 wks?
HIV Exposed
BF Child
YES NO
Î Continue CTX from 6w-18m
Î Assess at each follow up visit:
Does the child have any signs of HIV?

Î If clinically indicated, do RT and


refer child to ART clinic
Î 6 weeks after breastfeeding
cessation-re-test for HIV
(most infants will be ≥ 9m
HIV HIV
old by this time)
Positive Negative
Child Child ≥ 9m Child < 9m Child
Î Confirm with RT first, Î Stop CTX
2nd PCR test† Send PCR ‡ Send PCR Î If child is ill,
Î Refer child consider other
to HIV care & causes and
treatment follow up
Î Continue CTX
POS NEG
from 6w-18m RT at 18m

Fig. 3.1 Algorithm for Early Infant Diagnosis of HIV infection

51
3.5 Assessment and monitoring of severity of HIV infection and disease
progression

The WHO has developed an improved clinical staging system which lists clinical
conditions believed to have prognostic significance. There are four prognostic
categories (Table 3.4). This staging system is used in conjunction with the
immunological staging (Table 3.5) to determine when to initiate therapy.

Table 3.4: Presumptive and definitive criteria for recognizing HIV-related


clinical events in infants and children with established HIV infection
Clinical event Clinical diagnosis Definitive
diagnosis
STAGE 1
Asymptomatic No HIV-related symptoms reported and no Not applicable
clinical signs on examination.

Persistent Persistent swollen or enlarged lymph nodes >1 Clinical


generalised cm at two or more non-contiguous sites diagnosis
lymphadenopathy (excluding inguinal), without known cause
(PGL)
STAGE 2
Unexplained Enlarged liver and spleen without obvious cause. Clinical
persistent diagnosis
Hepato-
splenomegaly
Papular pruritic Papular pruritic vesicular lesions. Clinical
eruptions diagnosis
Fungal nail Fungal paronychia (painful, red and swollen nail Clinical
infections bed) or onycholysis (painless separation of the diagnosis
nail from the nail bed). Proximal white subungual
onchomycosis is uncommon without
immunodeficiency.

52
Clinical event Clinical diagnosis Definitive
diagnosis
STAGE 2 cont…
Angular cheilitis Splits or cracks on lips at the angle of the mouth Clinical
with depigmentation, usually responding to anti- diagnosis
fungal treatment but may recur.
Lineal gingival Erythematous band that follows the contour of the Clinical
Erythema (LGE) free gingival line; may be associated with diagnosis
spontaneous bleeding.
Extensive wart Characteristic warty skin lesions; small fleshy Clinical
virus grainy bumps, often rough, flat on sole of feet diagnosis
infection (plantar warts); facial, > 5% BSA or disfiguring.
Extensive Characteristic skin lesions: small flesh-coloured, Clinical
molluscum pearly or pink, dome-shaped or umbilicated diagnosis
contagiosum growths, may be inflamed or red; facial, > 5% of
infection BSA or disfiguring Giant molluscum may
indicate advanced immunodeficiency.
Recurrent oral Aphthous ulceration, typically with a halo of Clinical
Ulcers (≥2/6 mo.) inflammation and yellow-grey pseudomembrane. diagnosis
Unexplained Asymptomatic bilateral swelling that may Clinical
parotid spontaneously resolve and recur, in absence of diagnosis
enlargement known cause; usually painless.
Herpes zoster Painful rash with fluid-filled blisters, dermatomal Clinical
distribution, may be haemorrhagic on diagnosis
erythematous background; may become large &
confluent. Does not cross the midline.
Recurrent upper Current event with at least 1 episode in past 6 Clinical
respiratory tract months. Symptoms: fever, unilateral face pain diagnosis
infection (URTI) and nasal discharge (sinusitis) or painful swollen
eardrum (otitis media), sore throat with
productive cough (bronchitis) , sore throat
(pharyngitis) and barking croup-like cough,
persistent or recurrent ear discharge.

53
Clinical event Clinical diagnosis Definitive
diagnosis
STAGE 3
Unexplained Weight loss: low weight-for-age, up to -2 Documented loss of
moderate standard deviations (SDs), not explained by body weight
malnutrition poor or inadequate feeding and/or other of -2 SDs, failure to
infections, and not adequately responding to gain weight on
standard management. standard
management and
no other cause
identified during
investigation.
Unexplained Unexplained persistent (14 days or more) Stools observed and
persistent diarrhoea (loose or watery stool, three or documented as
diarrhoea more times daily) not responding to unformed. Culture
standard treatment. and microscopy
reveal no pathogens
Unexplained Reports of fever or night sweats for longer Documented fever
persistent than one month, either intermittent or of >37.5 ºC
Fever (intermittent constant, with reported lack of response with negative blood
or to antibiotics or antimalarials. No other culture,
constant for longer obvious foci of disease reported or found on negative malaria
than one month) examination. Malaria must be excluded in slide and
malarious areas normal or
unchanged CXR,
and
no other obvious
foci of disease.
Oral candidiasis Persistent or recurring creamy white soft Microscopy or
(after first 6 weeks small plaques which can be scraped off culture.
of life) (pseudomembranous), or red patches on
tongue, palate or lining of mouth, usually
painful or tender (erythematous form)

54
STAGE 3 cont…
Clinical event Clinical diagnosis Definitive
diagnosis
Oral hairy Fine small linear patches on lateral borders Clinical diagnosis.
leukoplakia of tongue, generally bilaterally, which do
not scrape off.

Lymph node TB Non-acute, painless “cold” enlargement of Histology or fine


lymph nodes, usually matted, localized in needle aspirate
one region. May have draining sinuses. for Ziehl Neelsen
Response to standard anti-TB treatment in stain. Culture.
one month.

Pulmonary TB Nonspecific symptoms, e.g. chronic cough, Isolation of M.


(History of contact fever, night sweats, anorexia and weight tuberculosis on
with adult with loss. In older children, productive cough sputum culture. +/-
smear-positive and haemoptysis as well. Abnormal
PTB) CXR

Severe recurrent Cough with fast breathing, chest in- Isolation of bacteria
bacterial drawing, nasal flaring, wheezing, and from appropriate
pneumonia grunting. Crackles or consolidation on clinical specimens
auscultation. Responds to course of (induced sputum,
antibiotics. Current episode plus one or BAL, lung
more in previous six months. aspirate).
Acute necrotizing Severe pain, ulcerated gingival papillae, Clinical diagnosis.
ulcerative loosening of teeth, spontaneous bleeding,
gingivitis or bad odour, and rapid loss of bone and/or
stomatitis, or acute soft tissue
necrotizing
ulcerative
periodontitis

55
Clinical event Clinical diagnosis Definitive
diagnosis
STAGE 3 cont…
Symptomatic LIP No presumptive clinical diagnosis. CXR: Oxygen saturation
bilateral reticulo-nodular interstitial persistently <90%.
pulmonary infiltrates present for more than May present with
two months with no response to antibiotic cor pulmonale
treatment and no other pathogen found. and may have
increased exercise-
induced fatigue.
Characteristic
histology.
Chronic HIV- History of cough productive of copious CXR; may show
associated amounts of purulent sputum (bronchiectasis honeycomb
lung disease only), with or without clubbing, halitosis, appearance (small
(including and crepitations and/or wheezes on cysts) and/or
bronchiectasis) auscultation; persistent areas of
opacification and/or
widespread lung
destruction, with
fibrosis and loss of
volume.
Unexplained No presumptive clinical diagnosis. Laboratory testing,
anaemia (<8g/dl), not explained
or neutropenia by other non-HIV
(<0.5 x 109/l) or conditions,
chronic or not responding to
thrombocytopenia standard
(<50 X 109/l) therapy with
haematinics,
anti-malarials or
anti-helminthics as
outlined in IMCI.

56
STAGE 4
Clinical event Clinical diagnosis Definitive
diagnosis
Unexplained Persistent weight loss not explained by poor or Documented
severe wasting, inadequate feeding or other infections and not weight loss of
stunting/ severe adequately responding in two weeks to standard >-3 SD +/-
malnutrition not therapy. Characterized by: visible severe oedema.
adequately wasting of muscles, with or without oedema of
responding both feet, and/or weight-for-height of -3 SDs, as
to standard therapy defined by WHO IMCI guidelines.
Pneumocystis Dry cough, progressive difficulty in breathing, CXR, typical
pneumonia (PCP) cyanosis, tachypnoea and fever; chest in- bilateral
drawing or stridor. (Severe or very severe perihilar
pneumonia as in IMCI.) Usually of rapid onset diffuse
especially in infants under 6 months of age. infiltrates;
Response to high-dose cotrimoxazole +/- microscopy of
prednisolone. induced sputum
or BAL or NPA
Recurrent severe Fever accompanied by specific symptoms or Culture of
bacterial infection, signs that localize infection. Responds to appropriate
e.g. empyema, antibiotics. Current episode plus one or more in clinical
pyomyositis, bone previous six months. specimen.
or joint infection,
meningitis but
excluding
pneumonia
Chronic herpes Severe and progressive painful orolabial, Culture and/or
simplex infection; genital, or anorectal lesions caused by HSV histology.
(orolabial or infection present for more than one month.
cutaneous of more
than one month’s
duration or visceral
at any site)

57
STAGE 4…cont…

Clinical event Clinical diagnosis Definitive


diagnosis
Oesophageal Chest pain and dysphagia (difficulty in Macroscopic
Candida swallowing), odynophagia (pain on swallowing appearance at
(or Candida of food and fluids) or retrosternal pain worse on endoscopy,
trachea, swallowing (food and fluids) responds to microscopy of
bronchi or lungs). specific treatment. In young children, suspect specimen from
particularly if oral Candida observed and food tissue or
refusal occurs and/or difficulties/crying when macroscopic
feeding. appearance at
bronchoscopy
or histology.
Extrapulmonary/ Systemic illness usually with prolonged fever, Positive
disseminated TB night sweats, weight loss. Clinical features of microscopy
organs involved, e.g. sterile showing AFB
pyuria, pericarditis, ascites, pleural effusion, or culture of
meningitis, arthritis, orchitis. Mycobacterium
. tuberculosis
from blood or
other relevant
specimen
except sputum
or BAL.
Biopsy and
histology.

Kaposi’s sarcoma Typical appearance in skin or oropharynx of Macroscopic


persistent, initially flat, patches with a pink or appearence or
blood-bruise colour, skin lesions that usually by
develop into nodules. Histology

58
STAGE 4…cont…

Clinical event Clinical diagnosis Definitive


diagnosis
CMV retinitis or Retinitis only: may be diagnosed by Histology or
CMV infection experienced clinicians: typical eye lesions on CMV
affecting another fundoscopic examination; discrete patches of demonstrated in
organ, with onset retinal whitening with distinct borders, CSF by culture
at age over 1 spreading centrifugally, often following blood or DNA-PCR.
month. vessels associated with retinal vasculitis,
haemorrhage and necrosis with onset at age
over 1 month.
CNS Fever, headache, focal neurological signs, Positive serum
toxoplasmosis convulsions. Usually responds within 10 days toxoplasma
to specific therapy. antibody AND
of available
single/
multiple
intracranial
mass lesions
on neuro
imaging (CT or
MRI).
Extrapulmonary Meningitis: usually subacute, fever with Isolation of
cryptococcosis increasing severe headache, meningism, Cryptococcus
including confusion, behavioural changes that responds to neoformans
meningitis cryptococcal therapy. from
extrapulmonary
site or positive
cryptococcal
antigen test
(CRAG) on
CSF or blood.

59
STAGE 4…cont…

Clinical event Clinical diagnosis Definitive diagnosis

HIV At least one of the following, Neuro imaging


encephalopathy progressing over at least two months in demonstrating atrophy
the absence of another illness: and basal ganglia
• failure to attain, or loss of, calcification, exclusion
developmental milestones, loss of other causes
of intellectual ability;
or
• progressive impaired brain
growth demonstrated by
stagnation of head
circumference;
or
• acquired symmetric motor
deficit accompanied by two or
more of the following: paresis,
pathological reflexes, ataxia, gait
disturbances

Disseminated No presumptive clinical diagnosis. Histology: usually


mycosis granuloma formation.
(coccidiomycosis, Isolation: antigen
histoplasmosis, . detection from affected
penicilliosis) tissue; culture or
microscopy from
clinical specimen or
blood culture.

60
STAGE 4…cont…

Clinical event Clinical diagnosis Definitive diagnosis

Disseminated No presumptive clinical diagnosis. Non-specific clinical


mycobacteriosis symptoms including
other than TB progressive weight loss,
fever, anaemia, night
sweats, fatigue or
diarrhoea; plus culture of
atypical
mycobacteria species from
stool, blood, body fluid or
other body tissue,
excluding lung.
Chronic Isospora No presumptive clinical diagnosis. Identification of isospora.

Chronic No presumptive clinical diagnosis. Cysts identified on


cryptosporidiosis modified ZN stain.
(with diarrhoea)
Cerebral or B cell No presumptive clinical diagnosis. CNS imaging: at least 1
non-Hodgkin lesion with mass effect;
lymphoma histology of
relevant specimen

61
Table 3.5: WHO classification of HIV-associated immunodeficiency in infants
and children

Classification of
HIV-associated Age-related CD4+ values/percentages
immunodeficiency ≤ 11 months 12-35 36-59 ≥ 5 years (cells/µl)
(%) months months
(%) (%)
Not significant >35 >30 >25 >500
Mild 30-35 25-30 20-25 350-499
Advanced 25-29 20-24 15-19 200-349
Severe <25 <20 <15 <200 or <15%

Total <4000 <3000 <2500 <2000


Lymphocyte cells/µl cells/µl cells/µl cells/µl
Count (TLC) *

*TLC criteria for severe HIV immunodeficiency requiring initiation of ART; suggested for use in
infants and children with clinical stage 2 and where CD4+ measurement is not available

3.6 Counselling in paediatric HIV and AIDS


a. Introduction
Counselling is an integral component of the holistic approach to caring for HIV-
infected/affected children and their families/caregivers. It is a continuous process that
starts from the point of contact with the facility for HIV-related services and
continues through out the life of the child with health and non-health sector support
services. Children and families/caregivers infected and affected by HIV and AIDS
have a number of challenges and needs and therefore require these services to cope.

Each counselling encounter is tailored to a specific need of the counsellee and may
include the following at different stages of the disease process:
• Counselling for HIV testing (pre-test and post-test counselling)
• Ongoing /Follow-up counselling for the other needs of the child and family

62
• Counselling for PMTCT including Early Infant Diagnosis
• Counselling for ART
• Counselling for disclosure
• HIV prevention counselling
• Bereavement counselling
Before discussing counselling in these situations, it is important to understand the
concept of counselling, how to do it and its benefits.

b. Definition of counselling
Counselling is a process by which a counsellor provides information and education
about a situation and helps the client to make an informed choice of what is best to do
in their situation. It is a helping process that involves a one-to-one communication
that is aimed at meeting specific needs of the individual. Thus for HIV infected and
affected children and their families since their needs differ from time to time,
counselling must be given at every visit. The counsellor must identify the reason for
each counselling encounter so as to maximise the benefit of the visit.

c. Benefits of counselling:
The benefits include the following:
• Meeting the specific need for which the counselling was sought
• Helping the child/caregivers and family members adopt a positive attitude to
HIV and its related complications
• Helping detect HIV-related conditions that could be effectively managed and
thereby improve the client’s life
• Offering opportunity for the child and his/her family to access other support
services (e.g., peer support groups and post-test clubs), nutritional support, and
ART.
• Equipping the client with the knowledge and skills to support other affected
persons

d. How to counsel
Care providers who counsel HIV infected and affected children and their
families/caregivers in different situations of care should be knowledgeable and skilled

63
in the aspect of the subject for discussion and must use appropriate counselling skills.
These skills are:
• Listening and learning skills
o Use helpful non-verbal communication
o Ask open questions
o Use responses and gestures that show interest
o Reflect back what the mother says
o Empathize – show that you understand how she feels
o Avoid words which are judgmental

• Building confidence and giving support skills


o Accept what a mother thinks and feels
o Recognise and praise what a mother and baby are doing right
o Give practical help
o Give a little relevant information
o Use simple and appropriate language
o Make one or two suggestions, not commands

As a general rule, interaction with the child should take place in the presence of a
parent and, when appropriate, with other family members or siblings, until the
counsellor has gained the confidence and trust of both the child and the caregivers.
Additionally, the presence of other family members enables the counsellor to observe
the reactions and interactions of both the child and family/caregiver. Children are
usually counselled by proxy, caregiver/parents are counselled and supported to
counsel the child. Older children can be counselled alone or with a family member
present, as the child prefers. However, counsellors should not discuss issues such as
sexuality without permission from parents/caregivers.

Parents should be continually informed and participate in the decision-making and


planning of appropriate care for their child, including decisions about where the child
should be treated. The counsellor must ensure that the social needs of the HIV-
infected and affected child are addressed by referring the parents to appropriate
organisations/institutions for socio-economic and spiritual support.

64
Confidentiality should be ensured during counselling and physical examination. The
protection of the child and his rights should be guaranteed especially when HIV
infection resulted from sexual abuse. Health services for adolescents should be youth-
friendly.

Effective counselling for adolescents should be culturally sensitive, tailored to the


developmental needs of youth, and in accordance with local values and laws.

e. Who should counsel


All health care providers involved in the care of HIV infected and affected children
and their families should be able to provide some basic counselling. Specific
counselling sessions such as HCT, Infant feeding options, EID, ART and adherence
should be carried out by trained counsellors to improve the quality of the counselling.

f. Different counselling situations


i. Counselling for HIV testing (pre-test and post-test counselling)
• Pre-test counselling: Pre-test counselling is carried out before testing for HIV
infection. Its objective is to obtain consent, preferably written, for HIV testing.
This counselling, in addition to providing basic information about HIV and the
test, should inform the counsellee about the limitations of the testing method,
the benefits of early diagnosis for the child, and the implications of a positive
HIV antibody test results for the family. If adolescents are counselled and
tested without an accompanying adult, their request for non-disclosure of the
result to the parents/caregivers must be respected

• Post test counselling: This involves discussing the result of the HIV testing
with the counsellee and its contents depend on the result-negative or positive.
The counsellor provides appropriate information, support and referral. If the
test result is negative, the counsellor will discuss how the child/family can
reduce their exposure to HIV infection. It is important to discuss the “window
period” and the need to repeat the test after 6 weeks to 3 months. If the test
result is positive, the counsellor should assist the counsellee to understand the

65
implications of the result and discuss their concerns about the disease. This
counselling should be arranged for at the time of taking blood for the HIV
testing. Results of a positive test should not be communicated through a phone
call. The number of post test counselling sessions needed by a child/family
varies and depends on how soon the child/family come to terms with the
positive result. The counsellor should be equipped to handle the spectrum of
reactions the child/family may express following a positive result; social
workers and psychologists may be of assistance.

ii. Ongoing /Follow-up counselling for the other needs of the child and family
HIV infected or exposed children should be followed-up to ensure optimal growth and
development. The follow-up counselling needs include:
• Nutritional support
• Growth monitoring and promotion
• Immunisation and other infant welfare services
• Prevention and management of the common disease conditions
• School-related problems of the HIV exposed and infected children
• Counselling and services for opportunistic infections and other HIV and AIDS
related conditions. This will include counselling for cotrimoxazole
chemoprophylaxis for PCP
• Support services to help families cope with the challenges of their status

iii. Counselling for the Prevention of Mother-to-Child Transmission of HIV


This counselling is aimed at reducing the risk of transmission of HIV infection from
mother to child. It can be carried out before or during the pregnancy or after the birth
of the child. It should be done at the earliest possible time, preferably prenatally so
that the woman gets pregnant at a time when her risk of infecting the baby is lowest.
The counselling involves discussing with the mother the different methods of
preventing mother-to-child transmission of HIV. The mother may need to be referred
for the different aspects of the services. The counselling should address the following:
• HIV testing & disclosure
• Delivery options
• Infant feeding options

66
• EID
• ARV prophylaxis
• Primary Prevention

The PMTCT services should be integrated into the health system.

iv. Counselling for ART


This counselling session is for the caregiver and the child where appropriate. It should
help them understand the following
• That the treatment will not cure the disease but reduce the multiplication of the
virus and improve quality of life
• The need for treatment, when to start, schedule and duration
• The different ARVs and their adverse effects
• Resistance to the drugs
• Adherence to the treatment
• Monitoring of treatment at home, community and facility

At different stages of the disease and during follow-up care visits, these issues should
be revisited to provide continued support for the child and the family/caregiver.

v. Counselling for disclosure


This involves counselling the parents/caregivers to support the process of disclosure
of the child’s HIV status to him/her with minimal negative impact. Parents who, for
different reasons may want to withhold disclosure from their children should be
counselled to understand the importance of the child knowing his/her status and
assisted to do so.

vi. Counselling for primary HIV prevention


HIV prevention counselling is a counsellor-led and client-focused exchange designed
to help individuals make behaviour changes that will reduce their risk of acquiring or
transmitting HIV. The counselling should provide information on the following:
• Behaviour change communication
• Encouragement of abstinence

67
• Condom use-promotion and provision
• Prompt treatment of STIs
• Family planning in HIV infected adolescents and couples.
.
vii. Bereavement counselling
• HIV-infected and affected children and their families face a major challenge
of coping with chronic ill health and death in themselves or their family
members. They need counselling and support to cope with these experiences.
Health workers should encourage open communication about what is
happening between the children themselves, the parents, and the health
workers. Parents must be reassured and understand that professionals are not
giving up on their children, but rather that there is nothing more that can be
done.
• The children and their families/caregivers require continual and ongoing
counselling and help after the death of a loved one. Parents and caregivers also
need support for their emotional reaction toward a dying child, and the dying
children themselves need help.
• Counselling should help the child cope with the terminal illness in themselves
or their parents. Where the parents are terminally ill the children need
counselling to cope with the loss of the parents and the new roles they may
have to take on in the absence of their parents and siblings. When children
lose someone they love, they need:
o Simple and age-appropriate information about what has happened
o To be listened to by someone who must be prepared to answer the
same question several times
o Reassurance that they will be loved and taken care of

Issues that need to be addressed in counselling children with terminally ill or deceased
parents include the following:
• Psychological stress
• Anxiety about their security and safety
• Lack of parental nurturing
• Lack of basic needs

68
• Loss of inheritance
• Need to work
• Less education and skills
• Mental health needs
• Emergency and long-term childcare

g. Steps for counselling HIV-infected and affected children and their families
There are certain steps that can be used as a basis for counselling HIV-
infected/exposed children and their families/caregivers. These steps vary with the
situation.
i. Child with unknown HIV status presenting with clinical signs of HIV infection and
or risk factors such as mother or sibling with HIV/AIDS
• Ascertain a child’s and/or mother’s or caregiver’s understanding of HIV
infection in general and, more specifically, MTCT
• Discuss the presumptive diagnosis of HIV infection in light of existing signs,
symptoms, and risk factors
• Explain the benefits of early awareness of HIV infection in the child’s life and
for the family
• Counsel and test child/parents to determine their HIV infection status
• If parents decline testing or decide to postpone the test, accept their decision
and reassure them that while their refusal will not compromise the
management of the child’s current illness, they and the health workers will be
missing the opportunity to plan for the child’s optimum care and support if the
child is HIV infected.

ii. Child known to be HIV infected and responding poorly to treatment


• Ascertain child’s and/or mother’s or caregiver’s understanding of HIV
infection
• Discuss the management of current problems and the reasons for poor
response to treatment
• Ascertain adherence to ARV therapy
• Refer child to a higher level of care for further investigations and/or
community-based or HBC programme, if necessary

69
• Discuss psychological implications of HIV for the child, mother, father, and
other family members
• Provide ongoing psychosocial support on coping with a chronic illness such as
HIV.

iii. Child known to be HIV infected and responding well to treatment


• Discuss follow-up, care, and risk factors for future illness.
• Discuss shared confidentiality and the social well-being of the child and the
family.

h. Challenges in the counselling of HIV infected/affected children and their


families
There are a number of challenges which a counsellor involved in paediatric HIV care
should consider and plan to mitigate their impacts. They include:
• Making and confirming the diagnosis in the child; some challenges here
include obtaining informed consent for testing, the window period, the types
of tests available and the need to wait for some time to confirm the result
• Disclosing the HIV status of the child; the parents/caregivers may have
challenges in this regard. These will include the appropriate language and skill
to communicate with the child, the age to disclose, the risk of the child
disclosing this status to peers
• Follow-up and other care for the children; challenges here include those of
getting the parents/caregivers to comply with the schedule of treatment, those
of reducing stigma arising from frequent visits to health facilities
• Starting and adhering to ART. The challenges here are those of providing the
relevant information that will enable adherence to the schedule of treatment.

3.7 Paediatric disclosure (talking to children about their HIV status)

Disclosure means to reveal, make known, make public or to share information on an


issue. Disclosure in this context means informing the child about his/her HIV status.
Disclosing information to children is a sensitive issue which must consider the needs,
feelings, beliefs of the child and those of the parent(s)/caregiver(s). It must however
be done to improve the management outcome. It is also important to consider the

70
current and evolving developmental and cognitive stages of the child as well as
existing family dynamics and communication.
Disclosure of the child’s HIV status is difficult for parents due to the following:
• Fear of impact of disclosure on child’s psychology and emotional health
• Fear of inadvertent disclosure to others by child
• Attempt to protect child from social rejection and stigma
• Guilt about the mode of transmission
• Difficulty coping with their own illness and those of their loved ones
• Established coping strategies within families (i.e. traditional silence around
illness and disease, limited communication within families and denial)
• Belief that the child will not understand
• Children as hope for future (avoiding thought of HIV keeps fatality at bay)

3.7.1 Importance of disclosure to children


These include:
• Reduction of the risk of development of fantasies about their illness
• Improvement of access to care and support services
• Enhancement of adherence to treatment and coping strategies
• Reduction of the negative psychosocial impacts of the disease

3.7.2 When and how to disclose


Disclosure is more than revealing HIV status. It also entails an ongoing discussion of
health and health-related issues. Parents/caregivers have the primary responsibility for
disclosure. They should begin the process as early as possible and continue to
dialogue with the child about the condition and related issues. Simple explanation of
the nature of HIV disease for younger children and disclosure about nature and
consequences for older children is recommended.

When to use the words “HIV and AIDS” will vary with the needs of the child and
family. The process can usually be started between the ages 5 and 7 years depending
on the child’s understanding and on the parent(s)/caregiver(s) consent. The process
should be gradual and the child could be led to guide the discussion. Alternatively, the
approach could be individualized to tailor the discussion according to the cognitive

71
development, use of tools and language for different developmental capacities
(drawing, story-telling, play, drama), level of maturity, coping skills and the child’s
health status. Health care providers should provide the necessary support, including
materials for the disclosure process.

3.7.3 Assisting families with disclosure


In preparing to disclose HIV status to a child, it is important for parents to have the
requisite knowledge to explain HIV infection and handle the related questions and
responses.
Arrangements should be made on appropriate place and time of disclosure, who needs
to be there, what will be said and the plans after disclosure. Issues of disclosure to
peers and others must also be addressed.

A follow-up arrangement to ensure school and family functioning, monitoring of


medical treatment and adherence should also be arranged. A role for support groups
and further on-going counselling should be outlined.

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CHAPTER 4
PROVIDER-INITIATED COUNSELLING AND TESTING IN
CHILDREN AND ADOLESCENTS

Introduction and Definitions


Provider-initiated HIV testing and counselling (PITC) refers to HIV testing and
counselling which is recommended by health care providers to persons attending
health care facilities as a standard component of medical care. The major purpose of
such testing and counselling is to enable specific clinical decisions to be made and/or
specific medical services to be offered that would not be possible without knowledge
of the child’s HIV status.

HIV testing and counselling should be recommended to all children seen in Paediatric
health services because children have a more rapid progression of HIV disease than
adults and signs and symptoms of HIV infection are often not specific. Without access
to care at least one-quarter of children with HIV die before the age of one year and
most die before reaching five years. It is a basic responsibility of heath care providers
to recommend HIV testing and counselling as part of the child’s routine clinical
management.

PITC for children also aims to identify unrecognized or unsuspected HIV infection
not only for children attending health facilities but also for children in their
community and home environments where opportunity allows. Health care providers
should therefore recommend HIV testing and counselling as part of a comprehensive
package of services provided to children and adolescents during all clinical
interactions in their health facility even if children do not have obvious HIV-related
symptoms or signs. Such children may nevertheless have HIV and may benefit from
specific preventive and/or therapeutic services. HIV control programs with

73
community outreach components should make efforts to implement PITC strategy as
a deliberate effort to scale up access to HIV care and support.

PITC is voluntary and the “three C’s” – informed consent, counselling and
confidentiality – must be observed. Special considerations apply for obtaining
informed consent from parents/caregivers in the case of children. In “opt-out”
approaches, caregivers and adolescents must specifically decline the HIV test after
receiving pre-test information if they do not want the test to be performed. In contrast,
with “opt-in” approaches, they must agree to the test being performed after pre=test
information has been received.

4.1 Recommendations for PITC in Children and Adolescent Health care services
PITC is recommended in all health facilities where children and adolescents receive
health care whether in public and private health settings, including medical and
surgical services, inpatient and outpatient facilities and mobile or outreach medical
services.
In the case of phased implementation of PITC an approximate order of priority maybe
as follows:
• Paedaitric in-patient and out-patient facilities including TB clinics

• Emergency Paediatric Unit

• Maternal and child health services (including immunization)

• Child birth services

• Services for most at risk population e.g. sickle cell disease, haemophiliacs,
oncology and STI clinics and OVC

• Surgical services

4.2 Pre-test information and informed consent for PITC in Children and
Adolescents
Facilities where PITC services exist should provide information and conduct risk
assessment to focus on prevention counselling for clients both prior to and after
receiving their test results.

74
a. Minimum information for informed consent for PITC in Children and
Adolescents

The following should be the minimum information that should be provided:


That HIV testing and counselling is being offered routinely and this has the benefits
of early diagnosis of HIV infection to allow for prompt interventions
• The test result will be treated confidentially and will not be shared with
anyone other than health care providers directly involved in providing services
to the patient
• The patient has the right to decline the test and that testing will be performed
unless the patient exercises that right
• Declining an HIV test will not affect the patient's access to services that do not
depend upon knowledge of HIV status
• In the event of an HIV-positive test result, prompt enrollment into HIV care
and support services
• An opportunity to ask the health care provider questions.
• For women and adolescent girls who are or may become pregnant should
include:
o The risks of transmitting HIV to the infant
o Measures that can be taken to reduce mother-to-child transmission,
including antiretroviral prophylaxis and infant feeding counselling
o The benefits to infants of early diagnosis of HIV.

b. Informed Consent for PITC for children


As minors( under the age of 18 years), children cannot legally provide informed
consent, thus informed consent for HIV testing should be obtained from the child’s
parent or guardian. Where there is no parent or legal guardian available, health care
providers should seek consent from an individual (sometimes known as a “substitute
decision-maker” or “surrogate decision-maker”) who has authority under the law to
make a decision based on the best interests of the child.

75
Although children have the right to be involved in all decisions affecting their lives
and to make their views known according to their level of development, attempts
should be made to explain to them what is happening and to obtain their assent.
Verbal communication is adequate for the purpose of obtaining informed consent.

4.3 Guiding principles and Special Considerations in adopting PITC strategy for
Children
The UN Convention on the Rights of the Child stipulates that “the best interests of the
child shall be a primary consideration” in all actions concerning children. This
includes decision-making about medical care. The purpose of HIV testing and
counselling should always be to promote the best interests and optimal health
outcomes for the child.

Where a child is extremely disadvantaged because he or she is orphaned, abandoned


or affected by mental or intellectual disability, he/she may be at increased risk of
discrimination, exploitation and unfavourable access to health care. HIV testing and
counselling should therefore be recommended for such children only where the
criteria of apparent HIV-related illness are satisfied, or maternal HIV-positive status is
known. HIV testing should only be offered for the purpose of providing the child with
appropriate HIV-related treatment, care and support.

Positive HIV test results in infants and young children in most instances indicates
maternal infection and, possibly, paternal infection. HIV testing and counselling
should therefore be recommended to parents and siblings of HIV-infected children,
where possible and appropriate, in the form of couples or family HIV counselling and
testing. Mothers should be specially informed that a negative test in the child does not
mean that the mother is not HIV-infected.

Health care providers must be adequately equipped to deal with the needs of children.
For example, counselling children requires skills that differ from adult and adolescent
counselling, including the ability to assess maturity and use age-appropriate language
(Refer to Chapter 3 in this Guidelines).

4.4 Special Considerations in PITC for Adolescents

76
Efforts to expand PITC in health facilities should include training and supervision for
health care providers on relevant laws and policies governing the consent for minors
to access clinical services, including when they can and cannot recommend an HIV
test to an adolescent independent of the consent of the adolescent’s parent or legal
guardian.
Where the law does not allow a sufficiently mature adolescent to give his or her own
informed consent to an HIV test, the health care provider should provide an
adolescent patient with the opportunity to assent to HIV testing and counselling in
private, without the presence or knowledge of his or her parents or legal guardians.
The pre-test information should be adapted to the patient’s age, developmental stage
and literacy level. If the adolescent provides assent, indicating that he or she
understands the risks and the benefits of HIV testing and would like to receive the
test, then the health care provider should seek the informed consent of the parent or
legal guardian.

In some situations, a parent or legal guardian may not be available to give consent on
the adolescent’s behalf. The health care provider may need to assess whether an
adolescent can request and consent to testing alone. The provider must always work
within the framework of existing laws and regulations and be guided by the best
interests of the patient.

4.5 Follow-up of Children and Adolescents where a test is declined


Declining an HIV test should not result in reduced quality or denial of services,
coercive treatment or breach of confidentiality, nor should it affect a person’s access
to health services that do not depend on knowledge of HIV status. Where testing is
declined, further opportunity should be created by offering assistance to access either
client-initiated testing or PITC in the future.

The patient’s decision to decline the HIV test should be noted in the medical record so
that, at subsequent visits to the health facility, a discussion of HIV testing and
counselling can be re-initiated.

4.6 Post-test counselling for HIV-positive persons

77
Ideally, post-test counselling should be provided by the same health care provider
who initiated HIV testing and counselling. Results should not be given in group
settings.

It is not acceptable practice for health care providers to recommend HIV testing and
counselling and to subsequently withhold or fail to convey test results. Although
patients can refuse to receive or accept results of any test or investigation, health care
providers should make every reasonable attempt to ensure that patients receive and
understand their test results in a confidential and compassionate manner.

The health care provider who provides post-test counselling in PITC should proceed
to actively link the child into care directly or through a pre-identified peer health
educator. Immediate enrollment into care should be emphasized with commencement
of cotrimoxazole prophylaxis. Subsequent effort should focus on providing testing
and counselling for the other members of the family including siblings of the index
child.

The focus of post-test counselling for families with HIV-positive test results is
psychosocial support to cope with the emotional impact of the test result, facilitate
access to treatment, care and prevention services, prevention of transmission and
disclosure to sexual and injecting partners. Health care providers should:
• Provide information about the result simply and clearly, and give the
client/caregiver time to consider it
• Ensure that the client/caregiver understands the result
• Allow the client/caregiver to ask questions
• Help cope with emotions arising from the test result
• Discuss any immediate concerns and assist in determining who in the
client/caregiver’s social network may be available and acceptable to offer
immediate support
• Describe follow-up services that are available in the health facility and in the
community, with special attention to the available treatment, PMTCT and care
and support services

78
• Provide information on how to prevent transmission of HIV, including
provision of male and female condoms and guidance on their use
• Provide information on other relevant preventive health measures such as
good nutrition, co-trimoxazole prophylaxis and insecticide-treated bed nets
• Discuss disclosure of the result, when and how this may happen and to whom
• Encourage and offer testing and counselling of partners and children
• Assess the risk of violence or suicide and discuss possible steps to ensure the
physical safety of family members
• Arrange a specific date and time for follow-up visits or referrals for treatment,
care, counselling, support and other services as appropriate (e.g. tuberculosis
screening and treatment, prophylaxis for opportunistic infections, STI
treatment, family planning, antenatal care, pain relief and access to sterile
needles and syringes).

4.7 Post-test counselling for HIV-positive pregnant women


In addition to the information described above, post-test counselling for pregnant
women whose test result is HIV-positive should address the following:
• Childbirth plans
• Use of antiretroviral drugs for the patient’s own health, when indicated and
available, and to prevent mother-to-child transmission
• Adequate maternal nutrition, including iron and folic acid
• Infant feeding options and support to carry out the mother’s infant feeding
choice
• HIV testing for the infant and the follow-up that will be necessary
• Partner testing.

4.8 Linkages and Referrals to other HIV services


HIV test results must be communicated with an explanation of the prevention,
treatment, care and support services available to the patient. Programmes for other
chronic illnesses and community-based HIV prevention, treatment, care and support
services are especially important resources and it is important to establish and
maintain active linkages with them.

79
At a minimum, referral should include providing the patient with information about
whom to contact as well as where, when and how to contact them. Patient referral
works best if the health care provider makes contact in the presence of the patient and
schedules an appointment, making note of the contact and the organization in the
patient’s file. Staff within the referral network need to routinely inform each other of
changes in personnel or processes which could impact upon the referral of patients.

4.9 Frequency of testing


The frequency of re-testing family members will depend on the exposure of the
individuals, the availability of human and financial resources.

Risks of HIV transmission to the infant are very high if the mother acquires HIV
during pregnancy or while breastfeeding.

HIV testing and counselling should generally be recommended to patients where


doubt exists about the patient’s prior testing history or the accuracy or veracity of
prior test results.

It is important that regular HIV testing does not become a substitution for prevention
behaviours. Health care providers should emphasize that people should sustain safer
behaviour.

80
Table 4.1: HIV-related services recommended for implementation of
comprehensive provider-initiated HIV testing and counselling in health facilities
(adapted from WHO)
• Individual or group pre-test information
• Basic care and support services for persons diagnosed HIV-positive:
o Education, psychosocial and peer support for management of HIV
o Periodic clinical assessment and clinical staging
o Management and treatment of common opportunistic infections
o Co-trimoxazole prophylaxis
o Tuberculosis screening and treatment when indicated; preventive
therapy when appropriate
o Malaria prevention and treatment, where appropriate
o STI case management and treatment
o Palliative care and symptom management
o Advice and support on other prevention interventions, such as safe
drinking water
o Nutrition advice
o Infant feeding counselling
o Antiretroviral treatment, where available
• Basic prevention services for persons diagnosed HIV-positive:
o Individual post-test counselling by a trained provider that includes
information about and referral to prevention, care and treatment
services, as required
o Support for disclosure to partner and couples counselling
o HIV testing and counselling for partners and children
o Safer sex and risk reduction counselling with promotion and provision
of male and female condoms
o Needle and syringe access and other harm reduction interventions for
injecting drug users
o Interventions to prevent mother-to-child transmission for pregnant
women, including antiretroviral prophylaxis
o Reproductive health services, family planning counselling and access
to contraceptive methods
• Basic prevention services for persons diagnosed HIV-negative:
o Post-test HIV prevention counselling for individuals or couples that
includes information about prevention services
o Promotion and provision of male and female condoms
o Needle and syringe access and other harm reduction interventions for
injecting drug users
o Post-exposure prophylaxis, where indicated

81
CHAPTER 5
MANAGEMENT OF COMMON CLINICAL CONDITIONS
ASSOCIATED WITH PAEDIATRIC HIV AND AIDS
Common childhood infections
HIV infection is associated with an increased frequency of common childhood
infections. These tend to be persistent or recurrent, severe, sometimes life-threatening
and respond poorly to treatment. They include acute respiratory tract, gastrointestinal
and muco-cutaneous infections as well as malaria which may be caused by bacteria,
viruses, fungi and protozoa. Table 5.1 shows common childhood infections in HIV
and AIDS, causative organisms, symptoms, signs and treatments.

82
83
Table 5.1: Common childhood infections in HIV and AIDS
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Bacterial Strept. pneumoniae, H. Fever, chills, cough and Clinical For out-patient therapy, For severe
pneumonia influenzae, Staph. aureus, pleuritic chest pain, Laboratory: CTZ pneumonia in
Moraxella catarhalis, difficulty/ fast breathing. blood culture. Ampiclox, amoxicillin or children <12
Klebs. pneumoniae and P. Crepitations, bronchial Chest x ray Amoxicillin/clauvullic acid. months old treat
aeruginosa breath sounds For in-patient therapy, PCP presumptively
Crystalline Penicillin & with CTZ.
Gentamicin. If facilities to
nd
2 generation cephalosporins as exclude PCP
second line. infections are not
available. If the
child on CPT
develops bacterial
pneumonia do not
treat with CTZ.
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Acute Respiratory viruses Fever, cough, vomiting, Clinical Amoxicillin or Amoxicillin/
Pharyngo Strept. pneumoniae, H. refusal of feeds, drooling Laboratory: clauvullinic acid.
– tonsillitis influenzae, M. catarhalis, saliva, inflamed tonsils/ Throat swab for 2nd generation cephalosporins.
Klebs. pneumoniae pharynx mcs

Acute Strept. pneumoniae, H. Fever, vomiting, cough, Clinical Amoxicillin or


otitis influenzae, Staph. aureus, ear-tugging; Hyperaemic Laboratory: Amoxicillin/clauvullinic acid.
media Moraxella catarhalis, tympanic membrane, Ear swab mcs Second generation
Klebs. pneumoniae purulent ear discharge cephalosporins. Ear wicking
Chronic Strept. pneumoniae, H. Ear discharge >14 days As above Refer to ENT specialist Hearing loss is a
suppurativ influenzae, S. aureus, M. X ray of complication
e otitis catarhalis, Kl. pneumoniae mastoid bone
media &P. aeruginosa
Acute Viruses – rota virus, Frequent watery stools, Clinical Rehydrate and treat Maintain adequate
watery Bacteria- Enterobacteriae, Laboratory: appropriately (SSS or ORS as nutrition
Diarrhoea E. coli, Campylobacter Stool mcs required)
jejuni, Serology

1
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Dysentery, Several possible Frequent watery stools, Clinical Rehydrate and treat Maintain adequate
pathogens: abdominal cramps bloody Laboratory: appropriately (SSS or ORS as nutrition
E. hystolitica, G. Lamblia, stools, fever, nausea and Stool mcs required)
Isospora belli, Crypt. vomiting, dehydration. Serological If antibiotics required:
parvum, Salmonella spp., diagnosis e.g. Ciprofloxacin
Shigella, C. pylori; C. Widal test Metronidazole and CTZ
jejuni, Cyclospora,
Microsporidium, C. Albendazole 400mg bd for 5
albicans, M. avium days to treat strongyloidiasis
complex (MAC), S. Oral Zinc therapy
Stercoralis
Malaria Mainly P. falciparum Fever, chills and rigor, Clinical Uncomplicated: Refer to tertiary
headache, nausea and Laboratory: Artemesinine Combination facility if necessary
vomiting detection of Therapy.
malaria parasite Complicated:
in the blood IV quinine, IM Artemether

2
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Sepsis S. pneumoniae, Fever may be only Careful clinical Broad spectrum antibiotics:
H. influenzae, presenting symptom; assessment Crystalline Penicillin Refer to tertiary
Salmonella, N. & Chloramphenicol; facility if necessary
meningitides, Shock Laboratory: Crystalline penicillin &
Staph aureus. Gram FBC Gentamycin
negative organisms such as Blood culture, Or
E. coli, Urine culture Ampiclox/ Gentamycin
Anaerobes Or
Amoxicillin/clauvullinate/
gentamycin.
Metronidazole
Pending mcs results
2nd and 3rd generation
cephalosporin can be used as
2nd line
If in shock, supportive therapy

3
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Meningitis S. pneumoniae Fever, headache, vomits, Careful clinical Crystalline Penicillin & Refer to tertiary
H. influenzae, irritability, altered assessment Chloramphenicol facility if necessary
Salmonella, N. sensorium, convulsions, Or
meningitides, nuchal rigidity, bulging Laboratory: Crystalline Penicillin &
Staph aureus fontanelle FBC, Blood Third generation
culture, LP for cephalosporins;
CSF analysis Supportive treatment

Measles Measles virus Fever, cough, red eyes, Clinical Supportive therapy Highly contagious;
coryza , typical maculo- Anti-pyresis (reduce fever) With
papular rash pneumonia, Vitamin A, antibiotics as complications,
diarrhoeal disease, indicated, adequate hydration refer to higher level
malnutrition and kerato- of care; Nutritional
conjunctivitis are common support
complications

4
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Chicken Varicella virus Fever, centrifugal (starts Clinical Supportive therapy
pox from trunk to extremities) Reduce fever;
umbilicated rash in crops Antibiotics for 2o infections

Skin infections
Impetigo Streptococcus spp, Staph. Fever, skin pustules Clinical Clean sore with antiseptics
contagio- aureus Drain pus if fluctuant
sum Ampicillin/cloxacillin
Scabies Sarcoptes scabei Intense itchy lesions most Clinical, 20% Benzyl benzoate applied Treat super-
prominent in inter-digital Lab: Micro- apply to total body, neck down imposed bacterial
webs, cleft; scopy on KOH nocte for 3 days infections with oral
Papular rashes or prep. of skin OR antibiotics;
generalised (Norwegian scrapings Permethrin cream 5% apply to Household
scabies) total body, neck down and wash members to be
treated
off after 8 – 14 hours. Repeat
simultaneously
after 1 – 2 weeks. even if
asymptomatic.

5
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Tinea Malassaezia furfur, Itchy circular lesions with Clinical Whitfield’s ointment 2% Miconazole
corporis raised edges, fine scaly 2 times daily for 3-5 wks cream apply bid to
Trichophyton rubrum area in the centre, loss of Laboratory: Oral Griseofulvin 10mg/kg/day skin
Tinea hair skin scrapings x 8wks
capitis stained with Oral Ketoconazole Take note of ARV
KOH 3.3-6.6 mg/kg/day once/day x (nevirapine)
2-4 wks interactions with
ketoconazole

Mollus- Pox virus Light-coloured nodule Clinical Leave alone unless super- Antibiotics with
cum with central umbilication infected. super-infection
contagio- commonly seen on face OR,
sum and trunk Electro-cautery
OR,
Use Liquid nitrogen application

6
Common Causative organisms Symptoms and signs Diagnosis Treatment Comments
childhood
infections
Warts Human papilloma virus Papules or nodules with a Clinical Apply Salicylic acid preparation
rough (verrucous) surface OR
Liquid nitrogen
OR
Cryotherapy
OR
Electrocautery
Seborrh- Allergic reaction to Yeast Greasy scales over scalp Clinical Selenium sulphide shampoo OR Secondary bacterial
oea infection (pityrosporum) and redness of cheek and Tar shampoo followed by infection may be
flexural aspects of body sulphur salicylic acid cream or common
1% hydrocortisone or
Ketoconazole cream

7
CHAPTER 6
COMMON OPPORTUNISTIC AND CO-INFECTIONS
Opportunistic infections (OIs) are caused by organisms, which in the immune
competent host would not cause significant disease. The causative organisms of OIs
in HIV-infected children include viruses, bacteria, fungi, protozoa and other parasites,
which often co-exist (Table 6.1).
Table 6.1: Common opportunistic infections in children with HIV and AIDS

Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects


infections organisms signs
Candida Candida White painless Clinical Nystatin 100,000-200,000 iu Nausea, vomiting,
infections: albicans plaques on the gargled or delivered to the diarrhoea, abdominal pain
buccal and or Laboratory: Wet cheeks in children 4-5 x day
A. Oral thrush pharyngeal mucosa mount microscopy for 14 days or pastiles Hepatotoxicity,
or surface of the using KOH (mucosal adhesive capsule agranulocytosis, seizures,
tongue that is not preparation. MAC) 4-5x/day for 7 – 10 days nausea, vomiting,
easily scraped off 1% aqueous solution of diarrhoea
gentian violet, local
application 2 x daily x 7 days
Fluconazole - oral
6mg/kg stat day 1 then
3mg/kg/day for 14 days

1
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
B. Oesophagitis As above White patches, in Suspected presence Fluconazole - oral With fluconazole,
mouth, retro-sternal of oro-pharyngeal 6mg/kg stat day 1 then hepatotoxicity, nausea,
pain on swallowing, thrush, 3mg/kg/day for 14-21 days vomiting abdominal pain,
food refusal, odynophagia Ketoconazole 3.3- pancytopaenia may occur
excessive salivation Oesophagoscopy 6.6mg/kg/day x 14-21 days Avoid use of ketoconazole
with NVP
Pneumocystis Pneumocystis Acute/sub-acute Clinical: Acute: Trimethoprim (TMP) Complications of drug
CXR: focal 20mg/kg/day PO or iv x 21
pneumonia jirovecii non productive treatment: Severe
interstitial days (3-4 divided doses)
(PCP) (carinii) cough, difficulty in Or reactions,
infiltrates and
Dapsone 2mg/kg daily max.
breathing mediastinal Stevens-Johnson
100mg/ day x 21 days
lymphadenopathy, Or syndrome, Toxic epidermal
ground glass Pentamidine 4mg/kg/day iv x
necrolysis,
appearance, 21 days;
Laboratory: Or Anaemia, hepatitis,
induced sputum or Clindamycin 10-30mg/kg/day
haemolysis in G6PD
i.v. tid x 14-21 days
bronchio-alveolar
For severe disease: PO2 deficient patients
lavage (BAL) for <90mmHg: add prednisolone
cytology. 2mg/kg/day x 7-14 days
Prophylaxis: CTX 6-
8mg/kg/day PO daily

2
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
Lymphoid Unknown, but Recurrent Cough, Clinical Steroids (prednisolone Complications of therapy
interstitial associated respiratory distress, 2mg/kg/day x 6 weeks, taper with prednisolone include
pneumonitis with co- parotid Laboratory: off) Hypertension, gastritis,
(LIP) infection with enlargement, Chest X Ray: adrenal insufficiency,
HIV and generalized reticulo-nodular Oxygen seizures, pseudo tumor
Epstein Barr lymphadenopathy, infiltrates, bilateral cerebri, hypokalaemia,
Virus hepatosplenomegal hilar/mediastinal Bronchodilators (salbutamol) fluid retention, glucose
y, digital clubbing, lymphadenopathy; intolerance
poor response to Chest physiotherapy
TB therapy Diagnosis of Referral to specialist
exclusion (paediatric pulmonologist)

3
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
Oral Herpes Herpes Recurrent, painful, Clinical; If severe; Nausea, vomiting,
simplex virus oral vesicular Laboratory: Tzanck i.v Acyclovir 5mg/kg/dose tid diarrhoea, headache,
1 and 2 lesions, shallow smear. or orally 40-80mg/kg/day tid malaise, rash, seizures,
ulcers Rising serum HSV for 5-10 days. renal dysfunction
Oesophagitis, antibody titres Topical antiseptics to avoid
cutaneous vesicles Increased ratio of secondary bacterial infections.
CNS Herpes Fever, altered state CSF:serum HSV Analgesics.
of consciousness, antibody IV Acyclovir 20mg/kg tid x
convulsions; there Viral isolation 21days
may be focal
neurological signs

4
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
Herpes zoster Varicella Painful vesicular Clinical IV Acyclovir 30mg/kg/day tds Refer intractable cases for
(Shingles) zoster lesions in a x 7 days specialist care.
dermatomal Analgesics – NSAIDS,
distribution, carbamazepine, amitriptyline
commonest on the Local appl of calamine lotion;
face and trunk Topical application of
Acyclovir cream
Toxoplasmosis Toxoplasma Fever, reduced Clinical: Pyrimethamine Complications of drug
2mg/kg/dose/day max 50mg x
gondii alertness, headache, Response to treatment - Megaloblastic
2 days then maintenance
focal neurological empiric therapy. 1mg/kg/day max 25mg + anaemia, pancytopaenia,
Sulphadiazine 50mg/kg/every
deficits, seizures, rash, Stevens Johnson
12 hours then treat 4 weeks
chorio-retinitis Serology: beyond resolution of Syndrome, nausea,
symptoms
rising IgG titre vomiting, abdominal pain,
Pyrimethamine + Folinic acid
5-20 mg 3 times weekly photosensitivity
+ Clindamycin 10-30mg/kg/
CT scan Folinic acid 5-20 mg
day tds x 6 weeks
Corticosteroids to reduce should be given to prevent
oedema/mass effect.
deficiency
Prophylaxis: CTZ

5
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
Cryptococcal Cryptococcus Headache, fever, Clinical Flucytosine orally Refer to infectious disease
meningitis neoformans delirium, neck pain, 100mg/kg/day for 14 days specialist
convulsion, Laboratory: followed by IV Amphotericin
photophobia CSF (Indian Ink B 0.7-1mg/kg/day x 2 wks
stain and Serology) Fluconazole 6mg/kg/day x 8
wks then 3mg/kg/day for life;
Cytomegalovirus Cytomegalovi Fever, cramps, Clinical Ganciclovir 5mg/kg iv bid x 2-
enteritis or colitis rus (CMV) watery stools with 3 weeks;
or without blood in
or CNS Laboratory: Biopsy
stools; delirium,
involvement lethargy, (intracellular Foscarnet 40-60mg/kg 8 hrly x
disorientation, inclusions) 2-3 weeks
malaise and
Serology
headache, neck
stiffness, Skull X ray Retinitis:
photophobia, CT Scan Same
cranial nerve
deficits, dysphagia
and odynophagia,
blurring of vision or
“floaters”

6
Opportunistic Causative Symptoms and Diagnosis Treatment Comments/ side effects
infections organisms signs
Mycobacterium M. avium spp. Disseminated form Clinical Clarithromycin 7.5mg/kg/dose Nausea and vomiting
Avium Complex – recurrent fever, bd or azithromycin 5-
chronic diarrhoea, Laboratory: 20mg/kg/dose once daily plus Optic neuritis
weight loss/failure multiple blood Ethambutol 15mg/kg/day for 6
to thrive, abdominal cultures months.
pain, Respiratory Biopsy of lymph Prophylaxis guided by CD4+
symptoms rare nodes for count
intracellular
inclusions

7
6.1 Tuberculosis
HIV infection increases a child’s susceptibility to infection with Mycobacterium tuberculosis.
The presence of TB may allow HIV to multiply quickly resulting in rapid progression of HIV
and AIDS. Pulmonary presentation is the most common form of TB in HIV-infected children
although other forms do occur. M. tuberculosis infection is one of the major causes of death in
HIV-infected children. There is a parallel increase in multi-drug resistant strains of M.
tuberculosis as a result of the HIV epidemic and consequently, the control of TB has become
more challenging.

6.1.1 Clinical Diagnosis


A high index of suspicion is required for the diagnosis of TB in HIV infected children.
• History
o Unexplained weight loss or failure to thrive
o Unexplained fever >21 days
o Cough >21 days
o Failure to respond to appropriate antibiotic treatment of presumed bacterial pneumonia or
meningitis
o Excessive night sweats
o Exposure to an adult with probable or definite open pulmonary TB

• Physical examination
o Pyrexia (temperature >37.50C)
o Weight loss
o Lymphadenopathy
o Abnormal chest signs
o Pleural effusion
o Signs of meningitis
o Abdominal distension
o Swelling and/or deformity of the spine

• Laboratory Investigations
o Radiographs of chest, spine and any other relevant area as indicated
o Tuberculin skin test e.g. Mantoux (≥5mm is positive)
o Ziehl-Neelson stain of sputum or early morning gastric aspirates for AFB
o Culture of sputum, gastric aspirate, pleural/ascitic fluid, CSF as indicated
o Lymph node biopsy
o FBC
o ESR
o PCR where available

6.1.2 Treatment and prophylaxis of TB in HIV-exposed or infected children


For treatment of TB in HIV-infected children see chapter 6.
For TB prophylaxis in HIV-exposed/infected children see chapter 8.

6.2 Hepatitis B and C


There is limited data on HIV and HBV/HCV infection in children. Infants born to mothers who
are co-infected with HIV and Hepatitis C are at a significantly increased risk of developing
Hepatitis C. Table 6.2 shows the clinical features and treatment of Hepatitis B and C.

9
10
Table 6.2 Features and treatment of Hepatitis B and C infections in HIV and AIDS
Condition Causative Symptoms Diagnosis Treatment Comments
agents and signs
Hepatitis B Hepatitis Acute: Clinical Supportive care; Perinatal transmission,
B virus Fever, right Chronic active hepatitis Treatment for life; through blood transfusion
(HBV) hypochondrial Laboratory: HBsAg, For pts <10 yr HAART in-eligible: and breast milk;
pain; jaundice, HBeAg, anti-HBs, anti- INF-α 5 Mega Units/m2 SC 3 x weekly x 3- Increased risk of hepato-
malaise HBe, anti-HBc 12 months; toxicity with ART
For <10 year eligible for HAART:
Chronic active LFTs HAART – 3TC, ZDV, EFV + INF-α There is increased risk of
hepatitis not For >10 years, HAART eligible: hepatic failure with
common in HAART (containing 3TC or FTC treatment interruption of
children + Tenofovir OR ARVs when drugs used
Adefovir +/- include 3TC and
INF-α 5 Mega Units/m2 Tenofovir
Prophylaxis: HBIG 0.06ml/kg + HBV
vaccine x 3 doses; Use Tenofovir with 3TC
HIV patient: recombinant HBV vaccine if or FTC in children <10
HBV markers negative. years if feasible
Hepatitis C Hepatitis Fever, right Clinical; Supportive care; Perinatal transmission,
C virus hypochondrial Labs: LFTs, Serology: Pegilated Interferon 1.5µg/kg/week sc; through blood transfusion
anti-HCV if >18 mo.
pain; jaundice Ribavirin 10.6mg/kg/day PO. and breast milk
HCV RNA-PCR if <18
mo. (Use ZDV, ddI with Ribavirin with caution Increased risk of
Liver biopsy due to side effects. Monitor ALT, FBC) hepatotoxicity with ART
12
CHAPTER 7
ANTIRETROVIRAL THERAPY IN INFANTS AND CHILDREN

Antiretroviral drugs reduce the ability of the virus to replicate thereby increasing the ability of
the body to fight infections. They do not provide a cure for HIV and AIDS but consistent and
appropriate use have been shown to prolong the lives of infected children.

7.1 Principles of Antiretroviral therapy in children


The principles underlying the use of antiretroviral drugs in children are different from those in
adults. The major differences are:
• Most HIV infections in children are acquired perinatally
• Perinatally acquired HIV infection occurs during the development of the infant's immune
system. Thus, both the clinical manifestations of HIV infection and the course of
immunological and virological markers of infection differ from those of adults
• Treatment of perinatally infected children may occur in the context of prior exposure to
ARVs for PMTCT
• Drug pharmacokinetics change during the transition from the newborn period to
adulthood, requiring specific evaluation of drug dosing and toxicity in infants and
children
• Optimising adherence to therapy in children requires specific considerations.

7.2 Classes of ARVs


The following are classes of ARVs:
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs) stop viral replication by
binding directly onto the reverse transcriptase enzyme preventing the transcription of
RNA to DNA
• Nucleoside reverse transcriptase inhibitors (NRTIs) incorporate themselves into the DNA
of the virus, stopping the building process. The resulting DNA is incomplete and cannot
create a new virus
• Nucleotide reverse transcriptase inhibitors (NtRTIs) act at the same stage of the viral life
cycle as the NRTIs, but do not require to be phosphorylated for effective antiretroviral
activity
• Protease inhibitors (PIs) work at the last stage of the virus reproduction cycle. They
prevent HIV from being successfully assembled and released from the infected CD4+ cell
• Entry inhibitors also called HIV fusion inhibitors prevent HIV particles from infecting
the CD4+ cell
• Integrase inhibitors interfere with the ability of the HIV DNA to insert itself into the host
DNA and thereby copy itself.

Fig 7.1 Life cycle of HIV showing the points of action of the ARVs

14
Table 7.1 Antiretroviral drugs

Non- Fixed-dose
Nucleoside Nucleotide
nucleoside combinati
reverse reverse
reverse Fusion ons
transcriptase transcriptase Protease inhibitors (PIs)
transcriptase inhibitors
inhibitors inhibitor
inhibitors
(NRTIs) (NtRTIs)
(NNRTIs)
Zidovudine Tenofovir Nevirapine Enfuvirtide Lopinavir-ritonavir 3TC/d4T/N
(ZDV, AZT)* (Disoproxil (NVP)* (T-20) (LPV/r)* VP
Lamivudine Fumarate Efavirenz Ritonavir (RTV) {as ZDV/ABC/
(3TC)* {TDF}) (EFV)* pharmacoenhancer}* 3TC
Stavudine Delavirdine Nelfinavir (NFV)* ZDV/3TC
(d4T)* (DLV) Saquinavir (SQV)
Abacavir Amprenavir (APV)*
(ABC)* Indinavir (IDV)
Didanosine Atazanavir (AZV)
(ddI) * Tipranavir
Zalcitabine Darunavir
(ddC) Fosamprenavir
Emtricitabine
(FTC)*

*Drugs indicated for use in children

15
Table 7.2: Nucleoside reverse transcriptase inhibitors (NRTIs)

ARV Strength/ Dosing Patient advice


Drug preparation
Zidovudine 10mg/ml oral solution 180-240 • Use with caution in the setting of anaemia. Do not use if HB < 8mg/dl.
2
(ZDV, AZT) 100 mg capsules mg/m /dose • Increased toxicity possible when used with other drugs that are associated
300 mg tablets b.d. to a with bone marrow suppression.
maximum of • Should not be administered in combination with d4T.
300 mg/dose • Use the higher dose with nervous system involvement.
• Storage: Room temperature and protect from light.
• No food restrictions.
Lamivudine 10 mg/ml oral solution 4 mg/kg/dose Store at room temperature.
(3TC) 150 tablets b.d. to a max.
of 150 mg/dose
Stavudine 1mg/ml oral powder 1 mg/kg/dose Not to be used with ZDV. Palatable solution that needs to be refrigerated and
(d4T) 15, 20, 30, 40 mg tablet b.d. to a max. shaken well before use.
of 40 mg/dose
Didanosine 10 mg/ml oral powder 90-120 • Suspension is not easy to use and should be avoided if possible. Requires
2
(ddl) 25, 50, 100 and150 mg tabs mg/m /dose refrigeration. Stable for 30 days.
125, 200, 250 and 400 mg b.d. to a • These may be enteric coated or combined with buffering agents or antacids.
enteric coated tabs maximum of • Should not be swallowed whole but should be chewed thoroughly, crushed or
dispersed in water or clear juice; in children tablets are not easily degradable
200 mg/dose
and may not have to be taken on an empty stomach.
• At least 2 tablets of appropriate strength must be used at any one time for
adequate buffering e.g. if the child’s dose is 50mg administer two 25mg
tablets instead of 50mg.
ARV Strength/ Dosing Patient advice
Drug preparation
Abacavir Suspension 20 mg/ml 8 mg/kg/dose • Parents must be warned about potential hypersensitivity reaction (signs of
(ABC) b.d. to a which may include fever, rash and difficulty with breathing).
maximum of • It should be stopped permanently if hypersensitivity reaction occurs.
300 mg tablets 300 mg/dose • No food restrictions.
• Tablets can be crushed, mixed with small amounts of water or food and
ingested immediately.
• Can be stored at room temperature but solution may be refrigerated.

Table 7.3: Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Drug Strengths & Dosing Patient advice


preparations
Nevirapine (NVP) 10 mg/ml solution 120mg/m2 od for 2 • Patients should be warned about the potential for severe life
weeks, then 120- threatening rash.
200mg/m2 bd to a • Metabolism of NVP may be increased with co-
200 mg tablets maximum of 200 administration of rifampin or rifabutin
mg/dose. • Ketoconazole should not be co-administered with NVP. No
food restriction needed. Oral suspension must be well
shaken.
Efavirenz (EFV) 30 mg/ml syrup 19.5 mg/kg/day syrup • Not recommended for use in children under the age of 3
years and weighing less than 10kg.
15 mg/kg/day capsule • Best given at bedtime to decrease the incidence of side
50, 100, 200 mg effects.
tablets > 40 kg: 600 mg • Can be taken with food, however when taken with a high
fat meal absorption is increased by 50%.

17
Table 7.4 Protease inhibitors (PIs)
Drug Strength & Dosing Patient advice
preparations
Amprenavir 15 mg/ml Not recommended for <4 Skin rash and fast breathing may occur.
(APV) years;
Children >4 yrs and <50
kg: 22.5 mg/kg/dose b.d.
or 17 mg/kg t.d.s max
1400 mg/dose
Lopinavir/r Oral solution: 80 mg 10-16 mg/kg/dose twice • Storage: Oral solution and capsules should be
lopinavir and 20 mg daily refrigerated, but can be kept at room temperature (up
ritonavir/ml to 25o C) if used within two months.
Capsules: 133.3 mg Maximum dose 400 mg • Caps to be swallowed whole & musn't’n be
lopinavir and 33.3 mg crushed.
ritonavir (Dosing refers to • No food restrictions.
Tablets 200 mg lopinavir Lopinavir component) • Has a bitter taste.
& 50 mg ritonavir • 200/50 tab; heat-stable; not require refrigeration.
Nelfinavir 50 mg/1.25ml scoop 60-75 mg/kg/dose bd, the • Administer with or after food; powder may be
(NFV) powder for oral higher dose/kg being for mixed with water, milk, formula feeds or pap; it
suspension. the bigger child, to a should not be mixed with acidic foods or juices.
200 mg/5ml maximum of 1250 • Tablets may be halved or crushed and dispersed in
Tablets 250, 625 mg mg/dose water or onto small amounts of food.

18
19
Table 7.5 Dosing schedule for fixed-dose combination containing d4T/3TC/ NVP

Weight range Dose


Formulation
(kg) (tablets)
AM PM
3 3.9 6/30/50 mg tablets 1 1
4 4.9 6/30/50 mg tablets 1 1
5 5.9 6/30/50 mg tablets 1 1
6 6.9 6/30/50 mg tablets 1.5 1.5
7 7.9 6/30/50 mg tablets 1.5 1.5
8 8.9 6/30/50 mg tablets 1.5 1.5
9 9.9 6/30/50 mg tablets 1.5 1.5
10 10.9 6/30/50 mg tablets 2 2
11 11.9 6/30/50 mg tablets 2 2
12 13.9 6/30/50 mg tablets 2 2
14 16.9 12/60/100 mg tablets 1.5 1
17 19.9 12/60/100 mg tablets 1.5 1
20 24.9 12/60/100 mg tablets 1.5 1.5
25 29.9 30/150/200 mg tablets 1 1
30 34.9 30/150/200 mg tablets 1 1

7.3 Initiating ART


The decision to start ART in children is complex. It depends on the age of the child, clinical
stage and immunological assessment.

7.3.1 Goals
The goals of ART in children are to:
• Stop and reverse progression of the disease by sustaining maximal viral suppression
thereby preserving the immune system and reducing the risk of opportunistic infections.
• Promote or restore normal growth and development
• Improve quality of life.
7.3.2 Considerations for ART in children include
• Multidisciplinary approach involving doctors, pharmacists, nurses, medical laboratory
scientists, counsellors, social workers, psychologists, nutritionists, data entry clerks,
outreach workers and others
• Identification of a primary caregiver who understands the disease and implications of
ART which include life long therapy, adherence issues, drugs storage and toxicities
• Access to nutritional support and family support groups including identification of an
informed secondary caregiver
• The status of disclosure to the child and other members of the family
• The choice of antiretroviral regimen should take into consideration possible limitation of
future treatment options and potential for drug resistance
• Factors influencing adherence to therapy
o Availability and palatability of paediatric formulations
o Impact of the medication schedule on quality of life, such as number of medications,
frequency of administration and the need to take with or without food
o Potential for drug interactions (including traditional medicines)
• Access to laboratory monitoring
• Prevalent coexisting conditions (e.g. malaria, malnutrition, TB, hepatitis B and C).
• Drug toxicity profile.

7.3.3 Pre-treatment evaluation


This includes:
• Confirmation of HIV infection
• Clinical evaluation of the child
o Detailed history and physical examination
o Determination of immunisation status
o Anthropometry (weight, height/length, MUAC, head circumference)
o Neuro-developmental assessment
• Immunological evaluation of the child (CD4+ count/CD4+%)
• Review of tuberculin skin test, chest x-ray, sputum/gastric aspirate for AFB to exclude
tuberculosis
• Review of other laboratory results LFTs, urinalysis, E/U, Serum creatinine, FBC (and
Serum lipids, serum Amylase, viral load if available)
21
• Development of child-specific adherence strategy.

7.3.4 Indications for initiation of ART

a) WHO recommendation for ART when CD4+ testing is available


i. Children with confirmed HIV infection with
WHO Paediatric stage 3 or 4 irrespective of CD4+% Or WHO paediatric stage 2 or 1 with
• CD4+ less than 25% (1500cells/µl) for children less than 12 months* or
• CD4+ less than 20% (<750cells/µl) for children 12-35 months
• CD4+ less than 15% (350cells/µl) for children 36-59 months
• CD4+ less than 15% (200cells/µl) for children ≥ 5 years

*All infants with a positive DNA-PCR should be closely monitored monthly for indications for
early initiation of therapy.

ii. Antibody positive children < 18months with no virological test*, but with:
• WHO paediatric HIV stage 3 or 4 irrespective of CD4+ %
• WHO paediatric HIV stage 2 only if CD4+% is less than 20
• WHO paediatric HIV stage 1: do not treat if no virological tests are available

* Must have confirmatory test at 18 months to continue with ART.

b) WHO recommendation for ART when CD4+ is not available


i. Less than 18 months of age:
• WHO paediatric HIV stage 3 or 4, irrespective of total lymphocyte count (TLC)
3
• WHO paediatric HIV stage 2 only if TLC less than 4000/mm (age <12 months)
3
<3000/mm (age 12-18 months) or if mother has severe symptomatic disease (WHO
adult stage 3 or 4), or died of AIDS
• WHO paediatric HIV stage 1: do not treat if no virological test available (but monitor
closely, monthly)

ii. More than 18 months of age:


• WHO paediatric HIV stage 3 or 4 irrespective of TLC

22
• WHO paediatric HIV stage 2 only if TLC is
o < 3000/mm3 if aged 18-35 months
o <2500/mm3 if aged 36-59 months or
o <2000/mm3 if age is ≥ 5 years.

7.3.5 First line ARV regimen


The combination of three or more drugs from at least two different groups is called Highly Active
Antiretroviral Therapy (HAART). The use of HAART is currently the standard treatment of HIV
infection in order to achieve the best possible suppression of viral replication and to arrest the
progression of the disease. There are many drug combinations that could be used. However, due
to limited availability of paediatric formulations, accessibility and affordability, the following are
recommended:

Table 7.6 First line ARV regimen

2 NRTI + 1 NNRTI
Recommended
AZT + 3TC + NVP/ EFV*

Alternative
D4T + 3TC + NVP/ EFV *
ABC + 3TC + NVP/ EFV *

*Only above age 3 years or >10 kg

See Annex I for paediatric weight-based dosing.

23
Table 7.7 Recommendations for the timing of ART following the initiation of TB
treatment with a rifampicin-containing regimen in HIV infected infants and children

Clinical stage Timing of ART following initiation Recommended


of child with of TB treatment (rifampicin- ARV regimenc
TB (as an containing regimen)a [B (IV)]*
event
WHO • Start ART soon after TB treatment In children <3 years :d
paediatric (between 2 and 8 weeks following • Triple NRTI first-line regimen
clinical stage start of TB treatment) (d4T or AZT + 3TC + ABC)
4b • or
• Standard first-line regimen of two
NRTIs + NVPc
In children >3 years:d
• Triple NRTI first-line regimen
(d4T or AZT + 3TC + ABC)
• or
• Standard first-line regimen of two
WHO With clinical management alone:
paediatric • Start ART soon after TB treatment
clinical stage (between 2 and 8 weeks following
c
3 start of TB treatment)
• If excellent clinical response to TB
treatment in first 2 to 8 weeks of
Where CD4+ is available: • Regimens as recommended above
Evaluate the possibility of delaying • Where ART can be delayed until
initiation of ART depending on after completion of TB treatment,
assessment of clinical status and initiation with a standard two NRTIs
CD4+, and clinical and + NNRTI first-line regimen (Table
immunological response to TB 6.7) is recommended
therapy

24
- Severe and advanced immunodeficiency: initiate ART soon after TB treatment (between 2 and 8 weeks following
start of TB treatment)
- Mild or no immunodeficiency: Initiation of ART may be delayed until after the completion of TB therapy; closely
monitor response to TB therapy and reassess
need for ART after TB therapy; if no improvement, consider starting ART

* Strength of recommendation /level of evidence.


a
Administration of CPT is important in children with TB/HIV co-infection.
b
All children with paediatric clinical stage 4 should be initiated on ART regardless of CD4+ criteria.
c
Careful clinical monitoring with laboratory support, if available, is recommended where NVP is administered
concurrently with rifampicin. This combination should only be used if there are no other options e.g in a
child with ABC hypersensitivity)
d
Because of lack of data the ranking of preferred or alternative ARV regimens is not possible.
e
EFV is not currently recommended for children <3 years of age, and should not be given to post-pubertal
adolescent girls who are either in the first trimester of pregnancy or are sexually active and not using
adequate contraception.

25
Table 7.8 Management of TB/HIV co-infection in children developing TB while on ARVs

Time of TB Underlying cause of TB Considerations for ART ARV regimen


diagnosis in following initiation of TB
relation to treatment (rifampicin-
ART containing regimen)

Child on TB attributable to primary infection Continue ART but assess for Continue on standard two NRTIs +
standard two (consider at any time during ART, need to change ART regimen - NNRTI first-line; if on NVP,a
NRTIs + depending on exposure to TB) response to TB therapy should substitute to EFVb if the child is aged
NNRTI first- be used to evaluate need for 3 years or above or
line regimen change ' Substitute NVP for ABC
diagnosed with
TB as part of IRIS (consider in first 6
TB months of ART) Refer to management
of IRIS

TB as a sign of treatment failure of Switch to second line regimen or refer


first-line regimen (consider only after at
to higher level of carec
least 24 weeks of ART)

Child on TB attributable to primary infection Assess for need to change Continue same regimen, consider
standard (consider at any time during ART, regimen - response to TB adding RTV to achieve full
second-line depending on exposure to TB) therapy should be used to therapeutic RTV dose (increase RTV
regimen evaluate need for changing or until same dose as LPV in mg)
(NRTI + stopping
boosted PI)
diagnosed TB as a sign of treatment failure of Consider consultation with experts for
with TB second-line regimen decision on salvage therapyc

26
a
Administration of co-trimoxazole preventive therapy (CPT) is important in children with TB/HIV co-infection. Careful clinical and
laboratory monitoring should be ensured where NVP is administered concurrently with rifampicin.
b
EFV is not currently recommended for children <3 years of age, and should not be given to post-pubertal adolescent girls who are
either in the first trimester of pregnancy or are sexually active and not using adequate contraception.
c
Few data are available to guide ART recommendations; research is urgently needed.

27
7.4 Antiretroviral drug toxicity

Most ART toxicities described in adults have also been reported in children, however there is
limited data on toxicities compared to adults. It is sometimes difficult to differentiate between
complications of HIV infection, ARVs toxicity and drug-drug interaction. Alternative
explanations for features suggestive of toxicities must be excluded before concluding that they
are ARV-related. Additional causes of these features include:
• Concurrent infection e.g. malaria with severe anaemia
• Immune reconstitution inflammatory syndrome (IRIS)
• A reaction to a non ARV drug such as co-trimoxazole in a child receiving CPT.
Table 7.9 Antiretroviral drug toxicity

ARV drug Primary toxicities Minor Monitoring and management


toxicities

Zidovudine Hematological (anaemia- Blue- For severe anaemia:


(ZDV, increasing macrocytosis over black
• Change to d4T or transfuse
AZT) time, neutropenia, discolorati
• Do not use if Hb < 7 g/dl or PCV <
thrombocytopenia), myopathy, on of
21%
gastro-intestinal intolerance nails,
For myopathy:
nausea
• Discontinue if CPK high
and
headache

Lamivudin Pancreatitis, liver toxicity, Skin rash, Discontinue if serum amylase elevated.
e (3TC) mild peripheral neuropathy headache Restart when resolved or change to
ABC

Stavudine peripheral neuropathy, Insomnia, With severe peripheral neuropathy,


(d4T) lipodystrophy/metabolic anxiety, abnormal serum amylase and
syndrome, lactic acidosis, panic transaminases, discontinue therapy
hepatitis, pancreatitis attacks

Didanosine Pancreatitis, painful peripheral Abdomina Discontinue if neuropathy is severe or


(ddI) neuropathy l cramps, serum amylase and transaminases are
diarrhoea raised. (Life-threatening lactic acidosis
-may may occur if combined with stavudine)
herald
onset of
lactic
acidosis

29
ARV drug Primary toxicities Minor Monitoring and management
toxicities

Abacavir Hypersensitivity reaction Lactic Discontinue therapy if hypersensitivity


(ABC) acidosis occurs and don’t re-start when resolved

Nevirapine • Skin rash, Stevens-Johnson Low-dose given over first 2 weeks


(NVP) syndrome, hepatotoxicity minimizes rash occurrence. If rash is
mild or moderate continue cautiously or
• DRESS syndrome (drug
substitute with EFV. If rash is severe or
rash, eosinophilia and
with hepatitis discontinue NVP
systemic symptoms
permanently.
manifesting as fever and
arthralgia)

Efavirenz Nightmares, Frank psychosis Dizziness • Rash may occur in 10%; may be
(EFV) in predisposed individuals, severe in <1% of patients;
rash, hepatitis
• CNS symptoms often resolve in 2-4
weeks.

• Night-time dosing is recommended to


reduce CNS side effects.

• Discontinue with hepatitis.

• Potentially teratogenic

Lopinavir/r Diarrhoea, skin rash Headache, Diarrhoea may occur, but is rarely
weakness severe

Nelfinavir Diarrhoea, lipid and glucose Diarrhoea occurs 10-30% at


(NFV) abnormalities and exacerbation commencement of therapy but often
of chronic liver disease resolves on its own

Drug-related adverse events may be acute, occurring shortly after a drug has been
administered, may be sub-acute, occurring within 1-2 days of administration or may be late

30
occurring after prolonged drug administration. These adverse events may vary from mild to
severe or life-threatening.
As a general principle:
• Mild toxicities do not require discontinuation of therapy or drug substitution.
Symptomatic treatment may be given e.g. anti-histamine for a drug rash.

• Moderate/severe toxicities may require substitution by a drug in the same class but
with a different toxicity profile

• Severe life-threatening toxicity requires discontinuation of all ARV drugs and the
initiation of supportive therapy.
See Table 7.9 for the management of ARV drug toxicities.
Inability to manage ARV drug toxicity may require referral to a higher level health facility.

7.5 Drug interactions


ARV Drug interactions
There are two groups of interactions:
• The ARV/ARV drug interactions
• Non-ARV/ARV drug interactions

7.5.1 Important ARV/ARV drug interactions


Zidovudine/stavudine combination is contra-indicated due to an antagonistic effect.

Ritonavir
• Recommended booster combination with ritonavir in children is Lopinavir/ritonavir
(LPV/r), as ritonavir increases the potency of Lopinavir
• Ritonavir has no effects on plasma levels of NVP, but it increases EFV levels by 21%
(EFV increases RTV levels by 18%)
• Ritonavir potentiates or increases plasma levels of NFV by 150%.

7.5.2 Important non-ARV/ARV interactions


a) Rifampicin

31
• Decreases plasma level of all PIs by at least 75% (except ritonavir, which it decreases
by 35%). Its use is not recommended with PIs currently used in children, except LPV/r
combination. (Additional ritonavir should be administered to provide standard
therapeutic dose)
• Rifampicin decreases plasma levels of EFV by (25%) and NVP by (37%). Not enough
information exists on dosage adjustments in children. Rifampicin can be used with EFV
in children over 3 years. The use of NVP and rifampicin should be considered only
when other options are not available.

b) Rifabutin
• Effects of Rifabutin on ARVs

o Rifabutin reduces levels of all PIs and NNRTIs by 15 to 35%.

• Effects of ARVs on rifabutin

o APV increases rifabutin level by 193%


o LPV/r increases rifabutin level by 300%
o EFV reduces rifabutin level by 35%

Not enough information exists on dosage adjustments in children.

c) Ketoconazole
Effects of ARVs on ketoconazole
• RTV increases its level by 300%, therefore use the lower end of dosing range for
ketoconazole if it must be used
• APV increases its level by 44% and it also increases APV level by 31%. No
recommendations for dose adjustment yet
• NVP decreases its level by 63% and ketoconazole increases NVP by 15%. The
hepatotoxic effect of NVP is increased and ketoconazole is not effective. The
combination is not recommended
• Fluconazole can be used with PIs and NNRTIs without dose adjustments unlike
ketoconazole.

32
Table 7.10: Drug interactions

Drug Potentially hazardous interaction Other interactions

Didanosine Antacids present in tablet formulation


may affect absorption of other drugs
Efavirenz Grape fruit juice, lopinavir, rifampicin,
ritonavir,
Lamivudine Sulfamethoxazole+Trimethoprim

Nelfinavir Phenobarbital, quinidine, rifampicin Phenytoin, ritonavir,

Nevirapine Lopinavir, rifampicin

Ritonavir Amitriptyline, carbamazepine, chloral Nelfinavir


hydrate, chlorpromazine, cyclosporin,
clomipramine, clonazepam, codeine
dexamethasone, diazepam,
erythromycin, fluconazole,
fludrocortisone, fluphenazine,
haloperidol, hydrocortisone,
ibuprofen, morphine, nifedipine,
pethidine, prednisolone, quinidine,
theophylline, verapamil, warfarin

Stavudine Zidovudine, Doxorubicin

33
7.6 Substitution within the first line ARV regimen
Substitution is the replacement of an identified offending drug causing toxicity with another
drug from the same class that does not have the same adverse effects. This is different from
switching which is the replacement of an ARV regimen because of treatment failure. An
example of a substitution is replacing AZT with d4T because of anaemia while an example of
switching is the replacement of a first line with a second line regimen. See Table 7.11.

Table 7.11 Severe toxicities associated with specific first line ARVs and potential first line
drug substitutions

First line First line regimen Most frequent significant Suggested first line
ARV toxicity for the ARV drug ARV drug
drug substitution
ZDV ZDV + 3TC + NVP Severe anaemiaa or D4T or ABC
ZDV + 3TC + EFV neutropeniab
Lactic acidosis ABCd
Severe gastrointestinal D4T or ABC
intolerancec
D4T d4T + 3TC + NVP Lactic acidosis ABCd
d4T + 3TC + EFV Peripheral neuropathy AZT or ABCf
Pancreatitis
Lipodystrophy/metabolic ABC
syndromee
ABC ABC + 3TC + NVP Hypersensitivity reaction AZT
ABC + 3TC + EFV
EFV ZDV + 3TC + EFV Persistent and severe central NVP
d4T + 3TC + EFV nervous system toxicityg
Potential teratogenicity
NVP ZDV + 3TC + NVP Acute symptomatic hepatitish EFVi
d4T + 3TC + NVP Hypersensitivity reaction Preferred substitution
ABC + 3TC + NVP Severe life threatening rash j of NVP to:
(Stevens-Johnson syndrome) A third NRTI or PI

34
a
Exclude malaria in areas of stable malaria, severe anaemia is defined as Hb < 7g/dl
b
Defined as absolute neutrophil count < 500/mm3
c
Defined as severe, refractory gastro intestinal intolerance that prevents ingestion of drugs e.g. persistent
nausea and vomiting
d
Re-initiation of ART should not include d4T or ZDV if possible therefore ABC is preferred
e
Substitution of d4T typically might not reverse lipodystrophy
f
In children, ABC or ZDV can be considered as an alternative.
g
Example persistent hallucinations or psychosis
h. Symptomatic NVP associated hepatotoxicity is very rare in HIV infected children before adolescence
i. Efavirenz is not currently recommended for children less than 3 years of age.
j. Severe rash is defined as extensive rash with desquamation, angioedema or a reaction resembling
serum sickness; or a rash with constitutional findings such as fever, oral lesions, blistering, facial oedema
and conjunctivitis. For life threatening rash do not substitute NVP with EFV because of class specific
toxicity.

35
7.7 Treatment failure
Treatment failure can be virological, immunological or clinical.
i) Virological indicators
Where CD4+ and clinical criteria for recognising treatment failure are conflicting, viral load
assessment can add useful information. Detectable viral load in the absence of poor adherence
to medication after 24 weeks of treatment is an indication of virological failure (for the
purposes of treatment failure, undetectable levels is defined as viral load <400 copies/ml).
The viral load should not be measured during a concurrent infection; preferably, it should be
measured at least one month after resolution of the infection.

ii) Immunological indicators


Treatment failure is characterised by a drop in the CD4+ cell count or %, to values at/or below
the age-related threshold for the initiation of treatment after initial immune recovery following
initiation of ART. Thus recognition of treatment failure on the basis of immunological values
relies on comparison with previous CD4+ cell count or %. Immunological failure should be
considered if CD4+ cell count or % falls to below:
• 20% for age <12 months
• 15% for age 12 – 35 months
• 10% for age 36 – 59 months
• 100 cells/mm3 for ≥ 5 years.
Where CD4+ values are not available a new or recurrent stage 3 and 4 event is an indication
of treatment failure. However, it is recommended that in the presence of pulmonary or lymph
node TB or severe recurrent bacterial pneumonia, patients should receive appropriate
treatment before treatment failure is considered.

iii) Clinical indicators


Clinical treatment failure should be considered when either new or recurrent stage 3 or 4
clinical events develop in a child on therapy (refer to Table 3.3).

iv) Total lymphocyte count (TLC)


Although the TLC is useful in the absence of CD4+cell count or % measurement to guide
when to initiate therapy it should not be used for the evaluation of response to antiretroviral
therapy because change in TLC is a poor predictor of treatment success.
36
Factors which contribute to treatment failure
• Poor adherence
• Inadequate drug levels
• Prior existing drug resistance
• Inadequate potency of the drugs chosen

Before treatment failure is considered in any child on ART, the following factors should be
taken into account:
• The child should have received the regimen for at least 24 weeks
• Adherence to therapy should have been assessed and considered to be optimal
• Intercurrent opportunistic infections should have been treated and resolved
• Immune reconstitution inflammatory syndrome (IRIS) should have been excluded
• Adequate nutrition should have been ensured.

Treatment failure needs to be differentiated from IRIS in the context of co-therapy. IRIS has
been observed in patients receiving anti-TB therapy who were initiated on ART. It has been
primarily reported in adults but it can also occur in children. It is defined as a paradoxical
clinical deterioration after starting HAART, resulting from improving immune system
interaction with organisms that have colonized the body during the early stages of HIV
infection. In spite of the clinical deterioration, there is improvement in CD4+ counts and
suppression of viral loads.

IRIS is characterized by worsening of disease after initial clinical improvement, with onset of
new systemic symptoms, especially fever. Other features include pulmonary infiltrates, the
development of peripheral and mediastinal adenopathy and worsening CNS manifestations in
patients with tuberculoma. These reactions may occur during the first three months of ART,
are generally self-limiting and last 10−40 days. Some reactions may be severe and require a
short course of treatment with prednisolone at a dose of 1-2mg/kg/day for 4-6 weeks.

Initiation of ART can also unmask previously undiagnosed infections such as hepatitis B or C
infections by improving the inflammatory response due to the improvement of the immune
system. In general, ART should not be interrupted for immune reconstitution syndrome.
37
7.8 Switching ARV regimen
Switching is the replacement of a first-line regimen with a second line regimen because of
treatment failure.
The second-line regimen should:
• Preferably include at least two new drugs, one or both of them from a new class in
order to increase the likelihood of treatment success and minimize the risk of cross-
resistance
• Be based on drugs expected to retain potency against the virus.

WHO recommends a regimen based on a PI, boosted where possible with ritonavir (RTV), and
combined with two new NRTIs (usually based on didanosine [ddI]) as the second-line regimen
for treatment failure.

Table 7.12: Second line ARV regimens

First-line regimen at Preferred second-line regimen


failure RTI components PI components b
(NRTI/NNRTI)a
2 NRTI + 1 NNRTI: ddIc + ABCd LPV/rf
• ZDV + 3TC + NVP
• d4T + 3TC + NVP Or
• ZDV + 3TC + EFV
• d4T + 3TC + EFV plus NFVh

ABC-containing ddIc + ZDV

Triple NRTI ddIc + EFVe or NVP

a
Continuation of 3TC in second-line regimens may be considered.
b
PI components are listed in order of potency/acceptability.
c
ddI may not need to be taken on an empty stomach in children.

38
d
It is not recommend to introduce AZT after use of d4T or vice versa.
e
EFV is not currently recommended for children <3 years of age or less than 10kg.
f
LPV/r is available co-formulated as solid and liquid.
h
Unboosted NFV may need to be used where heat stable LPV/r is not available; it should be taken with food to
improve bioavailability and high doses are needed in young children (e.g. >150 mg/kg per day).

7.9 Treatment interruption


Currently, there is limited data on treatment interruption in children. Interruption of ARV
therapy should not be encouraged, but may be indicated in some situations which include:
• Serious treatment-related toxicity
• Acute illnesses (e.g. severe diarrhoea and vomiting)
• Planned surgeries that preclude oral intake
• Patient or parent/caregiver requests after extensive counselling

Nevirapine tail
When short term interruption is indicated all therapy should be stopped at once. This can be
problematic with ARVs that have a long half-life for example NNRTIs (NVP, EFV). This
results in functional monotherapy that may lead to NNRTIs resistant mutations. To avoid this,
stop NNRTIs first and continue other ART drugs (NRTIs or PIs) for a period of one to two
weeks to allow NNRTIs to be cleared from the body.

7.10 Discontinuation of therapy


Under exceptional circumstances it may be necessary to discontinue ART. Such circumstances
include poor adherence and cases where the administration of medication is repeatedly
interrupted. Continuing suboptimal ART is not useful because it will lead to the emergence of
viral resistance. Consider discontinuation only after exploring all potentially corrective
measures, including intensive counseling, additional caregiver education, and family support.

7.11 Salvage therapy


A number of treatment approaches have been considered in clinical trial settings, although
largely in adults and where virological monitoring is possible. These include the addition or
substitution of new drugs (such as enfuvirtide [T-20]), mega-HAART (combination of five or
more drugs, including two or more protease inhibitors), strategic recycling of drugs, structured

39
treatment interruptions and the continuation of current therapy until additional drugs become
available. Refer patients to higher levels of care or ART specialists if necessary.

7.12 Drug resistance


7.12.1 Considerations on drug resistance
Infants and children may acquire resistant virus or develop resistance because of ARV
exposure for prophylaxis or treatment. In perinatal acquisition the infant acquires resistant
virus from the mother in utero, intrapartum or postpartum during breastfeeding.
The transmission of a resistant virus can occur:
• From an ARV-naive mother infected with resistant virus
• From a mother exposed to ARVs before becoming pregnant
• From a mother who has been exposed to ARVs during pregnancy either for her own
health or for prophylaxis of MTCT.

Treatment-related development of resistance in children is, as in adults, frequently related to:


• The use of suboptimal suppressive regimens
• Sub-optimal dosing
• Sub-therapeutic drug levels because of either poor adherence or
pharmacokinetic problems including drug interactions.

7.12.2 Considerations for minimizing the emergence of drug resistance


The emergence of HIV drug resistance (HIVDR) is of increasing concern in countries
where ART is widely used and represents a potential impediment to the achievement of
long-term success in the rapid scale-up of ART in resource-limited settings. Minimizing the
emergence and transmission of HIVDR is therefore essential in order to ensure the
efficacy of the limited number of ARVs available in many countries.

The following situations warrant resistance testing where available:


• Prior to initiating therapy in a patient exposed to possibly resistant virus
• In patients who fail to adequately respond to therapy

40
• In patients who experience viral “rebound” or a return of HIV RNA towards baseline
provided adherence is assured.

7.13 Adherence to ART


Medication adherence is a central feature in the success or failure of ARV therapy. Poor
adherence may lead to suboptimal levels of ARVs, which may facilitate the development of
drug resistance to one or more drugs in the regimen. Long-term poor adherence may lead to
cross-resistance to other drugs in the same class. Medication adherence of 95% (corresponding
to missing not more than 3 doses per month of a twice-daily therapy) or higher is associated
with the best chance of maximizing success of ART.

Adherence refers to a partnership between the patient, family and health care team to ensure
that medication is taken exactly as prescribed. This entails two-way discussions with the
patient and family to determine plans to incorporate medication dosing with current lifestyle.
Efforts to support and maximize adherence should begin before the initiation of treatment. The
development of an adherence plan and the education of children and their caregivers are
important first steps. Initial education should cover:
• Basic information about HIV and its natural history
• The benefits and side-effects of ARV medications
• How the medications should be taken and the importance of not missing any dose
• If medication is mixed with food the consumption of all food is important in order to
ensure administration of the full required dose.

The employment of additional methods may be necessary for young children, including the
tasting of medications, practising liquids measurement and training in pill swallowing.
Adherence, however, goes beyond initial education. It must be assessed at EACH visit, and
strategies to improve it should be discussed. Adherence in children is a special challenge
because of a number of potential barriers. These barriers need to be addressed prior to
starting therapy. Some of these include:
• Lack of disclosure to the patient or other family members
• Complex medication regimens
• Difficulty in measuring or administering medications
41
• Dietary requirements and restrictions
• Religious, cultural, and personal beliefs about taking medications
• High pill/liquid burden
• Multiple caregivers who may assume the other has given the medication;
• Difficulty with transportation to the clinic for refills and appointments;
• Travel away from home or having other family members visit;
• Poor palatability of ARVs
• Medication refusal
• Medication burn-out.

Assessing adherence is not simply asking if all medications are taken. It includes:
• A self-report/report from parents/caregivers
• Pharmacy refill counts
• Pill counts.

Additionally patients should be asked:


• What time they take the medication
• Whether they take it with food
• Who gives the medication
• What problems they have had with the medications
• Strategies they employ for remembering to take the medications.

Some strategies to improve adherence include:


• Having treatment partners (people that help remind the caregiver to administer the
medications)
• Home visits by HBC or outreach teams
• Integration of medication administration with routine daily activities (tooth-brushing,
prayers, meals, TV/radio shows, school hours)
• Sunrise/sunset
• Cell phone alarms/reminders
• Calendars, pillboxes, blister packs and labelled syringe

42
Viral load measurements can be used to assess adherence to medication. Directly
observed therapy has been successful in some settings. Medication doses should be closely
observed by the caregiver to ensure that drugs have been actually ingested by the child.

43
CHAPTER 8
CLINICAL AND LABORATORY MONITORING

Clinical and laboratory monitoring are essential parts of HIV and AIDS care in
children. These are required:
• At baseline (i.e. at entry into HIV care)
• During the care of patients who are not yet eligible for ART
• Starting ART
• Maintaining ART

8.1 Baseline clinical and laboratory assessment

All infants and children who are diagnosed with HIV infection should undergo a
baseline clinical and laboratory assessment in order to determine:

• Weight, height, head circumference and other measurements of growth

• Developmental status

• Nutritional status, including assessment of quality and quantity of intake.

• The clinical stage of HIV disease

• CD4+ count/CD4+% where available but where not available, do a TLC

• FBC, LFTs, lipid profile, serum E/U, creatinine, HBsAg, and HCVAb, chest
radiograph, pregnancy test for adolescents (where applicable)

• Eligibility for ART and other interventions such as cotrimoxazole preventive


therapy (CPT)

• The presence of active opportunistic infections

• The presence of co-existing diseases

• The need for referral to other support services.

44
8.2 Routine Monitoring of children who are not yet eligible for ART

The clinical evaluation of infants and children who are not yet eligible for ART
should be performed every three months and should include:

• Clinical evaluation

• Immunological evaluation (CD4+ count/ CD4+ %)

• Other investigations as clinically indicated

8.3 Routine monitoring of children on ART


The child should be seen:
• Two weeks after commencement of therapy
• Monthly for the first 6 months
• Thereafter every 3 months except otherwise indicated
See Table 8.1: Schedule for starting and monitoring children on HAART

The following should be conducted during follow-up visits:

i. Clinical assessment
• Growth monitoring using the national growth chart
• Physical examinations (with special attention to pallor, jaundice, oral cavity,
skin, lymph nodes, chest, liver and spleen)
• Developmental assessment
• Immunization status
• Nutritional assessment
• Psychosocial assessment
• Adverse ARV effects
• Review ARV dosages for every 10% increase in body weight

ii. Laboratory Evaluation


• CD4+ count every 3 months (except otherwise indicated)
• Viral load every 6 months
• FBC at one month and every 3 months (except otherwise indicated)

45
• LFTs at baseline and AST and ALT plus bilirubin levels every 3 months
unless otherwise indicated (for patients on NVP these should be done after 1
month of commencement)
• E/U, creatinine and urinalysis at baseline then every 3 months unless
otherwise indicated
• Serum lipid profile and amylase at baseline, at 3 months, and thereafter as
indicated, where possible.

See Table 8.2: Tiered laboratory capabilities for HIV treatment

iii. Assessment and monitoring of adherence


• Ask parents/caregiver, and count or measure volume of drugs left
• Inquire in a non-judgemental manner about barriers to adherence
• Check pharmacy drug pick-up records

Greater than 95% adherence to the drug regimen will ensure a good virological
response and prevent the emergence of viral resistance. For a child taking medication
twice daily, omitting more than one dose in ten days implies less than 95% adherence.
For further information see Section 7.13.

46
TABLE 8.1: Schedule for starting and monitoring children on HAART
Monthly x 6
Pre- Week 1 2 3 4 5 6 Every 3
Treatment 2 mo.
(Baseline) there-
after
Physical
Exam X X X X X X X X X
Adherence
Counselling X X X X X X X X X

Confirm X
HIV status
HIV-1
RNA(viral X X
load)

CD4+ X X X X

FBC X X X X
E&U* X X X X
LFT* X X** X X X
FBS X X X X
Serum X X
lipids* X X
& amylase*

Urinalysis* X X X X
Chest X- X
ray*

*And as clinically indicated


**For children on NVP

47
iv. Monitoring treatment and adverse drug reaction
For monitoring treatment and adverse drug reactions refer to Table 6.9.

Table 8.2: Tiered laboratory capabilities for HIV treatment

Primary health centre Secondary hospital Tertiary (referral) hospital


(Level 1) (Level 2) centre (Level 3)
• Rapid HIV Antibody • Rapid HIV antibody • Parallel Rapid HIV antibody
testing testing testing
• Hb/PCV • ELISA or Western Blot • ELISA or Western Blot
• Sputum smear for • FBC and differential • FBC
TB (refer if not • CD4+ cell count/% • CD4+ cell count/%
available) • Serum E and U, LFTs, • Serum E and U, LFTs, lipids
• Collection of DBS lipids • Sputum smear for TB
for DNA PCR • Sputum smear for TB • Collection of DBS for DNA
• Collection of DBS for PCR
DNA PCR • DNA PCR
• TB PCR
• Viral load testing
• Drug resistance testing

48
CHAPTER 9
SUPPORTIVE CARE FOR ORPHANS AND VULNERABLE
CHILDREN (OVC)
Introduction:
Beyond ART services, HIV infected and affected children (children orphaned and
vulnerable by HIV) require other services to grow up safe, healthy, happy and well-
educated with the chance to achieve their true potential. Uninfected but vulnerable
children are at greater risk of becoming HIV infected than their peers. About 1.8
million of the estimated 7 million Nigerian orphans as at 2005 were attributable to
HIV and AIDS alone.

9.1 Definitions and Context


The National Plan of Action for Orphans and Vulnerable Children (NPA) 2006-2010
(Ref: Federal Ministry of Women Affairs 2007) defines orphans and vulnerable
children (OVC) as follows:

An orphan: is a child (below the age of 18) who has lost one or both parents
irrespective of the cause of death. In the context of this guideline it would be death of
one or both parents due to AIDS related illnesses.

A Vulnerable Child: is a child whose safety, well-being and development are for
various reasons threatened. The definition of vulnerability varies from society to
society; and is therefore community specific. Vulnerability in the context of HIV and
AIDS is indicated in a child who as a result of HIV/AIDS affectation:
• is infected with HIV.
• is living with HIV infected parents but is not infected
• has inadequate access to educational, health and other social support
• has a chronically ill parent (regardless of whether the parent lives in the same
household as the child);
• lives in a household with terminally or chronically ill parent(s) or caregiver(s);
• lives with old/ frail grandparent(s) or caregiver(s)
• lives outside of family care, i.e. lives with extended family, in an institution or
on the streets;

49
The basic essential services identified by the National Plan of Action to be addressed
for all OVC include:
• Food and Nutrition
• Psychosocial care and support
• Education and vocational training
• Health care
• Shelter
• Household economic strengthening
• Protection including Legal support
Children should be involved as active participants in the provision of these services
within the family setting.

9.2 Food/Nutrition in HIV and AIDS


Malnutrition is a common condition in HIV infected children and is a major
contributor to morbidity and mortality. HIV infection can result in nutritional
deficiencies and growth and developmental failure, thus nutrition plays a critical role
in the care and support of HIV infected children. It is important to maintain adequate
nutritional status in HIV-infected children through nutritional management and
monitoring of growth parameters. Beyond the nutritional needs of the HIV infected
child there is a complex relationship between HIV and AIDS and chronic food
insecurity such that HIV affected households have longstanding challenges in meeting
their food and nutrition needs which also impact the uninfected OVC. Food/Nutrition
activities should aim at ensuring that the OVC receives enough food from early
childhood to ensure adequate nutrition for growth and development and an active and
productive life.

Goals of nutrition management for the OVC are:

1. Monitoring nutritional status using appropriate growth monitoring charts


2. Prevention or mitigation of factors associated with risk of malnutrition
3. Appropriate infant feeding practices
4. Nutritional supplementation and rehabilitation.

50
The discovery that HIV can be transmitted through breast milk and the fact that
breastfeeding is one of the most important child survival strategies have made safe
infant feeding one of the most complex, challenging and emotional aspects of
PMTCT programme. Among HIV infected mothers, the estimated additional risk of
transmission from breast milk, over and above the risk during pregnancy and delivery,
is about 15%for HIV-exposed babies who are breast-fed for up to 6 months and about
20% for babies who breastfeed into the second year of life.

Consequently, infant feeding counselling, long recognised as important for all


mothers, has become even more important with the emergence of HIV. Therefore,
mothers should be counselled and allowed to make an informed choice of the method
of feeding to be adopted for their children. The mother and her family should be
supported in her choice of feeding option by the health worker and the community.

9.2.1 Feeding options in the context of HIV infection


• Replacement feeding (breast milk substitutes) including multivitamins
when AFASS criteria are met:
o Commercial infant formula
o Home prepared milk such as modified fresh animal milk and full
cream milk
• Exclusive breastfeeding for 6 months with gradual introduction of
complementary feeds. During the transition period, breast milk should be
expressed and heat-treated
• Modified breastfeeding:
o Exclusive breastfeeding with cessation as soon as AFASS criteria are
met
o Expressing and heat-treating breast milk.
• Wet nursing by HIV negative surrogate mothers

Mixed feeding, i.e. concomitant feeding with breast milk and any other fluid or foods
including breast milk substitutes and water should be discouraged as it increases the
risk of HIV transmission to the infant.

51
9.2.2 Complementary feeding
After 6 months of age, milk feeds alone become inadequate to sustain growth.
Complementary feeds should therefore be introduced at the age of 6 months. The food
should be sourced locally and prepared appropriately. Multivitamins and
micronutrient supplements should be given.
Refer to National Guideline for Infant Feeding in the context of HIV and AIDS for
details.

9.2.3 Household food Security


HIV affected families and those caring for OVC often have limited resources to meet
food and nutritional needs of the children. Using locally available foodstuffs as well
as enhancing skills for agricultural production, food and nutritional support should be
provided for HIV infected and affected families. In addition, such families should be
linked with donor supported food security programs or activities of Community Based
Organisations (CBOs) and Faith-Based Organisations (FBOs).
For further details refer to the National Guidelines and Standards of Practice for
Orphans and Vulnerable Children 2007.

9.3 Psychosocial support (PSS)


HIV and AIDS impact upon the fundamental human attachments essential to normal
family life and child development as well as their ability to participate cooperatively
in home and community activities. A diagnosis of HIV infection in a child also has
the potential to disrupt the family stability by placing uncertainty over the family’s
future. Cultural taboos surrounding the discussion of AIDS and death often compound
these problems. Affected and infected children suffer anxiety and fear during the
years of parental illness, then grief and trauma with the death of a parent/family
member.

The care of the OVC should be comprehensive using a multidisciplinary approach and
should be family-centred to strengthen the family’s ability to cope with the child’s
illness and its psychological consequences. Appropriate and adequate PSS should
provide children with care that is suitable for their age and situation, and recognize
that children often respond differently to trauma and loss.

52
Psychosocial needs of children are as follows:
• Care, attention, security, love, nurturing, play, acceptance, a supportive home
environment and specific help to overcome their individual problems
• Simple and age-appropriate information about the loss of a loved one
• Someone who is prepared to listen and answer the same question several times
• Reassurance that they will be taken care of and loved

Psychosocial Assessment for anticipated family adaptation should include the


following:
• Child and family’s knowledge and reactions to the disease
• Beliefs, attitudes and expectations regarding treatment and outcome
• Coping ability during previous crises
• History of depression and/or non-prescribed drug and alcohol use
• Nature and stability of residential and occupational arrangements
• Quality of relationships between members of both nuclear and extended
family
• Level of disclosure – parent to child on both status of parent and child
• Socio-economic status of the family
• Socio-cultural factors or religious beliefs that might affect treatment decisions
and adaptation
• Sources of emotional and financial support
• Health status of other family members

9.3.1 Periods of psychosocial vulnerability


Psychological stress is heightened at the time of initial diagnosis, during episodes of
illness and during terminal illness.

a. At time of diagnosis:
The family’s response to the diagnosis of HIV and AIDS in a child includes shock,
denial, fear, guilt, disbelief, anger and sadness. Once the HIV status is accepted,
families experience grief reactions as they mourn the loss of their hopes and dreams
for the future, and some family members may develop depression that requires
intervention.

53
b. During episodes of illness:
As the child has episodes of illness, parents struggle with feelings of helplessness,
sadness and anger. It is during these episodes that the implications of the disease
become an emotional reality.

c. During terminal illness:


Dealing with terminal illness is one of the most challenging tasks in the care of the
OVC. During this time parents need assistance to ensure that their child receives
dignified end-of-life care in the hospital or at home.

9.3.2 Issues to address in psychosocial support for the OVC


i. Issues from the OVC’s perspective include:
• Dealing with chronic ill health, pain, and discomfort
• Being different from others
• Watching a family member battle terminal illness and caring for them
• Bereavement and its consequences
• Asking questions that are not answered or getting evasive answers
• Behavioural problems such as aggression, disruption, and/or restlessness,
truancy, depression and withdrawal
• Other problems such as bed-wetting, sleep disturbance and bodily complaints
with causes that may be difficult to ascertain.

54
ii. Issues from caregiver’s perspective
In Nigeria, where MTCT is the main mode of HIV transmission in children, the
mother who is invariably the primary caregiver is most often HIV infected.
Psychological issues she will need to deal with include:
• Dealing with her own HIV status and/or illness
• Dealing with the child’s HIV status and/or illness and the related feelings of
guilt, anger and hopelessness
• Deciding on whether or what to disclose to the spouse, child, relations,
neighbours, or school authorities
• Reproductive desires and decisions in the face of HIV
• Time away from work and implications for job security and earnings
• Concern about who will take care of the children after the caregiver’s death
• Fear of her own death.

iii. Challenges from healthcare provider’s perspective include:


• Not having the knowledge and skills to communicate effectively (including
counselling) with children
• Not knowing what information is developmentally appropriate
• Not having the time to develop and nurture a relationship designed to make a
child open up
• Not being aware of referral options

9.4 Education and Vocational Training


Schools provide children with a safe and structured environment, emotional support,
supervision of adults, and the opportunity to learn how to interact with other children
and develop social networks. Education acts as a ‘social vaccine against HIV and
AIDS as it delays sexual debut in girls who complete secondary education, and
provides opportunities for the OVC to receive age appropriate HIV prevention
messages.

Barriers that limit OVC access to education (e.g. mandatory payments for P.T.A
levies, uniforms, books or tuition fees) must be identified and tackled. Special
attention should be paid to the vulnerability of girls, by addressing the

55
disproportionate levels of risk they face when leaving school at an early age to act as
caregivers to ailing parents. Formal education should be the priority for all children,
except where it will be difficult to reintegrate the child into formal education.
However, older children should be provided with vocational trainings..

Educational activities must be arranged to cater for the following age


ranges/categories:
• 0-5 - Early childhood and learning stimulation,
• 6-17 - in school for either primary and/or secondary education support,
• 15-18 - out of school for vocational skills training support,
• Life skills education for all children especially age 10 and above.

9.5. Health care needs of OVC


Adequate access to age appropriate health care services should be ensured. Efforts
should be geared towards preventive, promotive, curative and rehabilitative health
care services.

9.5.1 Immunization
The following is recommended:
• All OVC should be checked to ensure they are fully immunised according to
the national immunisation schedule
• Children who have, or are suspected to have HIV infection but are not yet
symptomatic should be given all appropriate vaccines, including Bacillus
Calmette Guerin (BCG), measles and yellow fever vaccines
• Children with symptomatic HIV infection should not be given live vaccines
(BCG and yellow fever vaccine) except for measles and Oral Polio Vaccines
(OPV)
• Measles vaccine should be given twice, at 6 and 9 months for HIV-infected

See Table 9.1 for recommended immunization schedule for HIV-exposed, other OVC
and HIV-infected children.

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TABLE 9.1: Recommended immunization schedule for use in HIV-exposed or
infected children

Vaccine Asymptomatic Symptomatic Optimal timing of


HIV infection/Other HIV infection immunisation
OVC
BCG Yes No At birth
DPT Yes Yes 6, 10, 14 Weeks
OPV Yes Yes 0, 6, 10, 14 Weeks
HBV Yes Yes Birth, 6 and 14
weeks
Measles Yes Yes 6, 9 Months
Yellow fever Yes No 9 months
Remember to give 5 doses of TT to mother as recommended in the national
immunization schedule
* Immunization of OVC against pneumoccocal and H. influenzae infections is
recommended

9.5.2 Prevention of HIV Infection in children


Prevention of HIV infection in OVC especially adolescents should be a priority health
intervention. Programmes providing care for OVC need to ensure that vulnerable
children get age-appropriate effective HIV prevention messagesThis is especially true
for programs that target adolescents and older youth. Facilities and services should be
child and youth friendly.

9.5.3 Common medical problems of OVCs


Table 9.2 shows some common medical problems of OVCs, their causes and management.

57
Table 9.2 Symptoms of common illnesses, causes and their management

Symptoms Causes Management


Nausea Drugs, gastrointestinal Small frequent feeds, fluids between meals;
and infections, fever eat before taking medications, dry foods,
vomiting avoid sweet, fatty, salty, or spicy foods.
Sore mouth Herpes simplex, Keep mouth clean; clean with soft cloth or gauze in
aphthous ulcers, clean salt water. Give clear water after each feed.
thrush, Avoid acidic drinks and hot food.
gingivitis Give pap, sour milk or porridge, soft and mashed.
Ice cubes may help;
ice cream or yoghurt, if available
and affordable.
Chronic Infections, Rehydration using ORT, diet modification (e.g.
diarrhoea malabsorption, yoghurt rather than fresh milk), micronutrient
malignancies, supplements
drug-related
Persistent Infections, LIP, Nebulization with salbutamol/saline for
cough Bronchiectasis LIP, physiotherapy
Dermatitis Infections and Emmolients, corticosteroids, anti-histamines,
infestations, antiseptics
hypersensitivity, Keep nails short to minimize trauma and
malignancies secondary infection from scratching
Convulsions Infections and Anticonvulsants
infestations,
encephalopathy,
malignancies, Progressiv
multifocal leuko-
encephalophathy, metabo
disorders
Wounds Infections, pressure, Wound dressing, honey dressing, wounds,
malnutrition frequent turning and massage of pressure
areas

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i. Pain Management
Pain takes on special significance in children because it is very common but often
under-diagnosed and under-treated. A rational approach to pain management includes
the following:
• Clinical evaluation to elicit potential causes and type of pain
• Classification of the pain into mild, moderate or severe
• Treatment depending on the cause, type and severity
• Reassessment to ensure that optimal pain management is achieved and maintained.

Causes of pain in children with HIV disease include:


• Severe infections
• Spasticity secondary to encephalopathy
• Procedural pain
• Non-organic pain involving parts of the body e.g. abdomen
• Malignancies

Treatment
• Mild pain: Non-opiod e.g. paracetamol
• Moderate pain: Non-opiod e.g. paracetamol and NSAID
• Severe pain: narcotic analgesics like morphine, codeine

ii. Prophylaxis for opportunistic infections

a. Primary prophylaxis
This is drug administration before onset of a disease. Due to the high susceptibility of
HIV-infected children to infections, primary prophylaxis should be offered to them. In
the HIV-exposed or infected child these include co-trimoxazole preventive therapy
(CPT) and isoniazid preventive therapy (IPT). The time to start the prophylaxis
against these infections will be determined by:
• Age of the patient
• Time of maximum susceptibility to the infection
• Availability of laboratory support to diagnose the infection.

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Cotrimoxazole preventive therapy (CPT)
Co-trimoxazole (CTX), a combination of trimethoprim (TMP) and
sulphamethoxazole (SMX) is used as prophylaxis against PCP in HIV-exposed and
infected children.

CPT lowers the risk of the following diseases


• Pneumocystis jirovecii pneumonia (PCP) (formerly called Pneumocystis
carinii pneumonia)
• Toxoplasmosis
• Isosporidiosis
• Strept. pneumoniae infections
• Salmonella species infections

Criteria for CPT


• All infants delivered to HIV positive mothers, from 6 weeks of age or at first
contact if later until the HIV status is known
• HIV-infected infants regardless of CD4+ % or clinical symptoms. Continue
prophylaxis until they are 5 years of age regardless of symptoms, CD4+ % or
good immune response to ART
• HIV-infected children between 1 and 4 years with WHO stages 2, 3 & 4 or
CD4+ < 25%. Continue prophylaxis until patient is five years old regardless of
symptoms or CD4+% or good response to ART
• Adolescents and children ≥ 5 years with CD4+ count < 350 or Stage 3 or 4
regardless of CD4+ cell count
• Where CD4+ count is not available, WHO Stages 2, 3 and 4.

NB: Start CTX two weeks before commencing ART

CTX regimen
CTX regimen: TMP (150mg/m2/day) and SMX (750mg/m2/day) orally once daily.
Table 9.3 gives the weight-based dosages.

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Table 9.3: Weight-based dosage in Co-trimoxazole Prophylaxis for children

Weight of CTX tablets CTX CTX tablet CTX tablet


child (kg) 20mgTMP/100m suspension 80mg 160mg
Daily dosing g 40mg TMP/500mg TMP/800mg
SMX Paediatric TMP/200mg SMX regular SMX double
strength SMX/5ml strength strength
1 2
(120mg) (240mg) (480mg) (960mg)

1-4 1 2.5 ml ¼ -

5-8 2 5 ml ½ ¼

9-16 - 10 ml 1 ½

17-50 - - 2 1

>50 - - 2 1
1
= use other options for children over 9 kg
2
= use regular or double strength tablet for children over 16 kg

CTX side effects


Mild:
• Skin rash and neutropaenia respond to temporary interruption of therapy.
Severe:
• Anaphylaxis
• Stevens – Johnson Syndrome (blistering rash involving skin, mouth, red eyes)
• Liver failure

These are medical emergencies that require that drug be stopped and the child
immediately referred to a tertiary hospital.
Alternative drug to CTX: Dapsone at a dose of 2mg/kg daily should be substituted.

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Isoniazid preventive therapy (IPT)
The following is recommended for the prevention and control of TB among HIV-
infected children:
• Chemoprophylaxis should be started in children who have positive Mantoux
test (>5mm but <10) result but normal chest radiographs and no other signs of
extra-pulmonary TB
• Where Mantoux testing is not available, prophylaxis should be considered for
the following categories of children:
o Household contacts of TB patients
o Institutionalised children
Prophylaxis entails a 6 months course of isoniazid given at a dose of 5mg/kg (not
more than 300mg/day).

b. Secondary prophylaxis
This is used to protect a person who has suffered from an OI, from recurrent episodes
of the infection.
Indications:
• Any child with history of PCP and/or toxoplasmosis should continue with
prophylaxis of CPT for life
• Post-cryptococcal meningitis should have fluconazole prophylaxis for life

For patients on primary or secondary prophylaxis, the adverse effects of the drugs
should be monitored at each follow-up visit.

c. Prophylaxis against malaria


Although immuno-suppressed children are susceptible to severe forms of malaria, it is
not recommended that chemoprophylaxis be given to prevent the disease. These
children are also eligible to use Insecticide Treated Nets which should be provided as
part of the basic care package for OVC

9.6. Protection including Legal Support


OVC are susceptible to having their rights abused or denied. Supportive care
addressing protection issues should include efforts to ensure that a child is safe from

62
any abuse, neglect, stigma, discrimination, or exploitation. Services should confront
and minimize the reality of stigma and social neglect faced by OVC as well as abuse
and exploitation (e.g trafficking, denial of inherited property).

Protection services include: facilitating birth registration and identification


documents; preventing children from being in abusive and exploitative situations, and
removing children from such situations. Refer to National OVC Guidelines and
Standards of Practice2007.

9.7 Shelter
The HIV and AIDS epidemic overloads impoverished communities to the point where
many children are left without suitable shelter or care. It is therefore necessary that
holistic care for OVC should ensure adequate living environment for the child that is
free of abuse, neglect and exploitation. Institutional care should be the last option as it
is neither optimal for child development, sustainable nor cost effective. Efforts should
be made to re-integrate OVC back to their families/communities of orientation.

9.8 Economic Strengthening


The diminished productive capacity of infected parents/caregivers and increased
utilization of cash resources for necessary household purchases in seeking health care,
makes families living with OVC economically unable to cater for their physical and
material needs. They should be linked to community-based groups that provide
economic/household strengthening services.

The focus of household economic strengthening should be to:


• Build the socio-economic capacity of families to support orphans and
vulnerable children
• Establish micro-finance projects that benefit households caring for orphans
and other vulnerable children
• Improve agricultural productivity and efficiency among households with adult
members who are ill or have died
• Provide apprenticeships, vocational and life skills training for young people
• Increase access to labour-saving technologies

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• Strengthen social safety net to support the elderly and the infirm
• Establish effective community-based mechanism for monitoring the socio-
economic security of orphans and other vulnerable children and their families.

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CHAPTER 10
HIV INFECTION IN ADOLESCENTS
Introduction

WHO defined adolescents as individuals aged 10–19 years and young people as those
aged 10–24 years. It is a period of transition between childhood and adulthood
characterized by major physical, emotional and cognitive changes. Significant
changes also occur in the relationships between the adolescent, her/his family
members and peers. Although adolescents may be physically and sexually mature,
they may not be emotionally and cognitively matured enough to anticipate the
undesirable effects of sexual relationships such as unwanted pregnancy and STIs,
including HIV and AIDS.

Adolescents and young people are a special group to consider in HIV control
programmes because of the high disease burden among them, their care-free attitude,
ignorance and high risk behaviours. These behaviours include drug and substance
abuse, violence, cultism, street life and early sexual exposure which may be casual,
unprotected and with multiple sexual partners and they may be victims of rape.

10.1 Transmission
Adolescents acquire HIV infection mainly through sexual transmission, transfusion of
infected blood or blood products and intravenous drug use. About 5% of perinatally
infected children may survive into adolescence without ARV.

10.2 Clinical features, diagnosis and management of HIV in adolescents


Adolescents are categorized according to their sexual maturity rating (SMR) using the
Tanner Staging (Annex IIa and IIb). Those in Tanner Stages 1-2 are managed using
paediatric ARV guidelines, while those in Stages 3 and above are managed using
adult ARV guidelines.

10.3 Antiretroviral therapy


A minimum of three drugs including an NNRTI or a PI is typically used as first line
treatment. Based on availability, accessibility, affordability, efficacy and ease of

65
administration, see the adult ART Guidelines for recommended ARV regimens for
older adolescents. For younger adolescents see Tables 7.6 and 7.12.

10.4 Challenges related to HIV and AIDS in adolescents


The challenges in the care of adolescents include issues associated with adherence to
care and treatment, disclosure to them and their families, prevention of HIV
transmission particularly in those who are sexually active and the use of
contraceptives. Other challenges include obtaining consent for medical treatment,
issues of confidentiality and protection, lack of insight into HIV infection and
inability to understand the long-term implications of the disease.

10.5 Counselling for ART in adolescents


It is not uncommon that children below the age of consent (<18 years) who are
sexually active acquire HIV infection and present for care. This situation is different
from those children who acquired HIV infection through vertical transmission. The
common dilemma is when and how the parents or guardians should be informed. This
is more difficult when the child does not want disclosure to parents/guardians but
would like to benefit from ART and is willing to have an HIV test.

In view of the complicated nature of ART and the need for family support to maintain
good adherence, it is recommended that:

• Every effort should be made by the counsellor to discuss with the


adolescent about the need to involve the parents/guardians
• Additional counselling time should be given to the adolescent to allow for
deep understanding of the implications of ART

10.6 Prevention
No single strategy works best to prevent HIV transmission among young people, the
best programmes are built on the synergy of multiple interventions. These
programmes should provide young people with youth friendly information including
moral values, counselling, skills, and services for prevention and treatment of STIs
and HIV. They should be encouraged to abstain from early sexual relationships, avoid

66
casual sex, use condoms, shun violence and cultism, avoid substance abuse (including
alcohols) and have premarital HCT.

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CHAPTER 11
PREVENTION OF HIV INFECTION
Introduction
There is ample evidence globally that well-designed prevention programmes can
reduce the incidence of HIV infection.
There are four major sources of HIV infection in children.
• Transmission from mother to child during pregnancy, labour/delivery or
through breastfeeding
• Transfusions of blood or blood products, or transplanted tissue or organs
obtained from HIV-infected donors
• Using contaminated skin piercing instruments or sharps
• Sexual transmission

Since most paediatric HIV infections are vertically acquired, reduction in the
prevalence of the infection will require specific efforts to prevent the disease in the
adult population.

11.1 Specific strategies for prevention of HIV infection in children


11.1.1 Prevention of transmission of mother-to-child transmission (PMTCT)
HIV among children is a growing problem, particularly in the countries hardest hit by
the AIDS pandemic. MTCT accounts for over 90% of infections in children. PMTCT
programmes provide opportunities not only to prevent infections but also to identify
and provide care for HIV exposed and infected children, their mothers and families.
PMTCT of HIV is now a high priority and has been the rallying point for enhanced
prevention efforts in children.

The National Policy on HIV and AIDS includes:


• Primary HIV prevention
• Prevention of unintended Pregnancy among HIV positive women
• Prevention of HIV transmission from HIV infected mother to newborn babies
and infants:
o Use of ART in pregnancy
o Safer delivery practices

68
o Safe infant feeding practices
o Use of post-exposure prophylaxis in infants*
• Providing care and support to HIV infected women, their infants and their
families

*Neonatal dosing (for PMTCT only)


NVP 2mg/kg stat (within a week preferably within 72 hours of birth), plus ZDV 4
mg/kg/ dose 12 hourly for 6 weeks.

N/B: Premature infant < 34 wk EGA: 2mg/kg per dose of ZDV 12 hourly for
the first 2 wk of life, then 3 mg/kg per dose 12 hourly x 6 weeks.

i. Management of HIV exposed infant


(i.) Immediate newborn care
• Wipe baby’s mouth and nostrils with gauze at delivery of the head
• All babies, regardless of HIV status of mother should be handled with gloves
until maternal blood and secretions are washed off
• All babies, irrespective of their HIV status should be kept warm after
delivery
• Immediately after birth, baby should be washed with warm chlorhexidine
solution or wiped dry with a towel or surgical cloth to remove maternal body
fluids
• There should be no suction of the newborn with a nasogastric tube unless
indicated e.g. meconium stained liquor. Where suctioning is required, it is
better to use a mechanical suction unit (at a pressure below 100mmHg) or
bulb suction if possible, rather than mouth operated suction
• Vitamin K and BCG should be administered, ensuring injection safety.
• Find out from the mother her feeding choice and support her. For mothers
who are not aware of their HIV status, encourage breastfeeding.
• Start NVP and ZDV prophylaxis

(ii.) Follow-up of the exposed infants

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The follow-up care recommended for HIV exposed or infected children are as
follows:
• All HIV-exposed babies should be seen within one week of birth including
those delivered outside health facilities.
o Check feeding practice and give support where needed
o Check mother’s and infant’s health status
• Establish monthly follow up schedule for the infant for the first year of life
o Commence CPT at 6 weeks
o Monitor weight, length, and head circumference
o Check PCV
o DBS for DNA PCR at 6 weeks/first contact if child <9 months, or
antibody testing at 18 months
o Ensure mother is practicing her feeding choice appropriately
o Multivitamins (containing Vitamin A) preparations are given to the
HIV exposed infants for nutritional support until HIV is excluded
o Ensure that the infant’s immunization schedule is up to date
• Assess all children for OIs and treat appropriately
• Cessation of breastfeeding at 6 months for exclusively breastfed babies
• By 6 months complementary food should be started. The babies should be
assessed within two to four weeks to see if there is evidence of growth
faltering
• After age 12 months, follow up should be every 3 months through 24 months,
after 2 years and every six months thereafter
• Refer HIV-infected children for appropriate services (ART, Psychosocial care
etc).

11.1.2 Universal precautions


Universal precautions are simple standards of infection control practices to be
observed in the care of all patients at all times, to reduce the risk of transmission of
blood borne infections, they include:
• Careful handling and disposal of sharps
• Hand washing with soap and water before and after all invasive procedures

70
• Use of protective barriers such as gloves, gowns, aprons, masks, goggles for
direct contact with blood and other body fluids
• Proper disinfection of instruments and other contaminated equipment
• Proper handling of soiled linen

Proper planning and management of supplies and other resources are essential in
reducing occupational risks of HIV infection. Such measures should include risk
assessment, post-exposure follow-up protocols and first aid. In addition, introducing
measures to prevent or reduce stress, maintain an optimum workload, orientate new
staff and provide education and supervision can reduce occupational risks.

11.2 Post –exposure prophylaxis for children


11.2.1 Assessment of exposure and need for referral
Following an exposure, the health care provider should ascertain whether the
exposure is associated with a potential risk of HIV transmission and whether it has
occurred within the previous 36 hours. Potential exposures that may pose a risk of
HIV transmission include:
• Break in the skin by an object that is visibly contaminated with blood or that
has been in a blood vessel
• Bite wounds that result in bleeding in the person bitten or the person biting
• Splash of blood, visibly blood-stained fluids, or other potentially infectious
body fluids to a mucosal surface
• Exposure of non-intact skin to blood or blood-stained body fluids
• Exposure of mucous membranes or of non-intact skins to semen or blood
during sexual exposure/abuse

11.2.2 Assessment of risk of transmission


Assessment of risk of transmission and decision- making about treatment should
include consideration of the following factors:
• Nature of exposure – HIV transmission is only known to occur after exposure
to blood, visibly blood-stained body fluids, or other infectious body fluids,
including semen during sexual exposure

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• Time of exposure: If the exposure occurred greater than 72 hours before
presentation, PEP is unlikely to be beneficial in reducing transmission. Early
administration of PEP correlates with greater efficacy.

Based on this assessment of risk, the health care provider should discuss with the
child or parent(s)/caregiver(s) the potential risk of HIV exposure. When the risk of
exposure is not significant, the provider should reassure the family and not initiate
PEP. If the risk is sufficient to warrant PEP, a careful discussion of the PEP regimen
and follow-up care should take place.

11.2.3 Factors determining use of ARVs following exposure to infected body fluid

Depending on the results of the HIV tests the following actions should be taken:

• If the source person is HIV negative


o no further PEP is necessary for the child
• If the child is HIV positive
o no further PEP is necessary
o the child should be referred for further counselling and management on
a long-term basis
• If the child is HIV negative and the source person is HIV positive,
o continue ARVs for a period of four weeks
o repeat child’s HIV test at 3 and 6 months after the initial test
o if child sero-converts during this period then provide appropriate care
and counselling and refer for expert opinion and long term
management.
• If it is not possible to determine the HIV status of the source person
o assume that the source person is positive and proceed according to
guidelines for PEP
11.2.4 ARVs to be used in PEP
The exposure should be classified as “low risk” or “high risk” for HIV infection as
below:

Low risk:

• Solid needle, superficial exposure on intact skin

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• Small volume (drops of blood) on mucous membrane or non-intact skin
exposures
• Source is asymptomatic or VL <1500 copies/ml

High Risk:

• Large bore needle, deep injury, visible blood on device, needle in patient
artery/vein
• Large volume (major blood splash on mucous membrane or non-intact
skin exposures)
• Source patient is symptomatic, acute sero-conversion, high viral load

Immediately after exposure all exposed individuals should take PEP according to the
assumed risk. Those of low risk should take 2-drug combination and those with high
risk should take a 3-drug combination. Where the risk cannot be ascertained, a 2-drug
combination should be used.

11.2.5 Initiation of PEP


Key issues about PEP should be discussed with the family and the child as soon as
possible. Issues to discuss will include:
• Potential benefits
• Potential toxicities associated with medications
• Potential side effects associated with medication
• Instruction on how and when to give the medication
• Importance of adherence to medication regimen
• Nature and duration of medication regimen and monitoring schedule

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Table 11.1: Recommended drug regimen for Post-exposure prophylaxis

Recommended 2-Drug Combinations Recommended 3-Drug Combinations

• ZDV ( 180 mg m 2/ dose twice • Any of the 2-drug combinations + EFV 1


daily) + 3TC (4 mg/kg/dose twice mg/kg/dose or a Protease Inhibitor (EFV
daily) should be avoided if pregnancy is suspected or
if child is less than 3 years.)

• d4T (1 mg/kg/dose twice daily) + • Preferred combination is: + EFV (15 mg once
2
3TC (4 mg/kg/dose twice daily) daily) or LPV/RTV (230mgm /57.5mg/m
2
/dose twice daily).

The chosen regimen is continued for 28 days or until the results of HIV tests for the
exposed child and contact person are known to be negative.

Table 11.2: Recommended schedule of investigations following exposure

Period Recommended Investigations

Baseline - HIV screening

- FBC

- LFTs

- Serum E/U, creatinine

Two weeks - FBC

- LFTs

- Serum E/U, creatinine

Six weeks - HIV screening

Three months - HIV screening

Six months - HIV screening

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11.3 Post-sexual exposure prophylaxis

There is not enough evidence to recommend prophylaxis against infection following


casual sexual exposure. However in the event that there has been sexual abuse or rape
then it is recommended that the victim be counselled and provided with the PEP
drugs. It is important to try and determine the HIV status of the perpetrator. If this is
not possible then it may be assumed that the perpetrator is HIV positive and the
victim is provided with treatment for high risk exposure as discussed above. In the
event of rape it is important to arrange for counselling and support to be provided to
the victim. The victim needs to be provided with information regarding STIs,
pregnancy and legal matters.

Children should be instructed in school and at home about potentially risky exposures
and how to avoid them. All health workers should discuss reduction of potentially
risky behaviours in all children in a manner that is appropriate to their age and
developmental stage as a routine component of paediatric care.

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CHAPTER 12
LEGAL AND ETHICAL ISSUES

Introduction
Issues for legal and ethical consideration in paediatric HIV infection include the
following:
• Consent for HIV testing
• Confidentiality and disclosure of HIV status; children have a right to
confidentiality and to be consulted according to their maturity and capacity to
understand the issues that pertain to their health
• Discrimination/ stigmatisation
• Respect for the human rights and dignity of those afflicted
• Consent for medical research
• Access to care and support

12.1 Children and the Law


There are limited national documents on ethical and legal issues related to HIV
infection in children. Although Nigeria’s constitution does not specifically mention
the rights of the child on HIV infection, its importance is expressed in the Child’s
Right Act.

12.1.1 The National Child Health Policy (2005)


This has the general goal of reduction of mortality attributable to HIV and AIDS in
children. The specific objectives are:
• Ensure survival of infants of HIV-infected mothers
• Reduce paediatric HIV and AIDS infections particularly through PMTCT
• Ensure optimal care, support and treatment of HIV-infected and affected
children.

The Strategic/Policy thrusts of the policy to achieve these objectives are:


• Government shall promote screening of all pregnant women for HIV infection
in all health facilities (public and private) through voluntary counselling and
testing (HCT)

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• Government shall promote the delivery of HIV prevention messages during
antenatal care and post-partum visits in all facilities
• Government shall ensure that obstetric and medical care for pregnant HIV
positive women is appropriately modified and strengthened in order to reduce
the risk of MTCT
• Government shall promote PEP for the infants of HIV sero-positive mothers
• Government shall provide affordable ARVs to children infected with HIV and
AIDS in line with the National ART programme
• Government shall work in collaboration with partners and related agencies to
build capacity of health workers in counselling HIV-infected mothers on
infant feeding options
• Government shall ensure that the use of BMS does not spill over to the
majority of mothers who are HIV-negative or of unknown status. In that
regard, commercial formula used for infants of HIV-positive mothers shall not
be displayed and health workers shall be the only ones to demonstrate feeding
with BMS to HIV positive-mothers.

12.1.2 The UN Convention on the Rights of the Child


This is applicable to all children irrespective of their HIV infection status. The
convention enjoins all nations to take necessary measures to protect children from all
forms of physical and mental violence, abuse or negligent treatment.

12.1.3 The UNAIDS International Guidelines on HIV AND AIDS and human rights
This has as its aim, ensuring that the creation of positive rights based response to HIV
and AIDS is guaranteed. These represent the collective recommendations of experts
from the health, human rights, government and civil society, including people living
with HIV and AIDS on how human rights should be protected and promoted,
respected and fulfilled in the context of HIV and AIDS. These recommendations,
which also serve as guidelines are:
• Based on existing human rights principles translated into concrete measures
that should be taken as part of an effective HIV and AIDS strategy
• Not a formal treaty, but are based on international human rights treaties that
must be observed by all states that have ratified them

77
• Welcomed by the UN Commission on Human Rights and by human rights,
development and health organizations around the world.

The recommendations are as follows:


1. States should establish an effective national framework for their response to HIV
and AIDS which ensures a co-ordinated, participatory, transparent and accountable
approach, integrating HIV and AIDS policy and programme responsibilities across all
branches of government.

2. States should ensure, through political and financial support that community
consultation occurs in all phases of HIV and AIDS policy design, programme
implementation and evaluation and that community organizations are enabled to carry
out their activities, including in the field of ethics, law and human rights, effectively.

3. States should review and reform public health laws to ensure that they adequately
address public health issues raised by HIV and AIDS, that their provisions applicable
to casually transmitted diseases are not inappropriately applied to HIV and AIDS and
that they are consistent with international human rights obligations.

4. States should review and reform criminal laws and correctional systems to ensure
that they are consistent with international human rights obligations and are not
misused in the context of HIV and AIDS or targeted against vulnerable groups.

5. States should enact or strengthen anti-discrimination and other protective laws that
protect vulnerable groups, people living with HIV and AIDS and people with
disabilities from discrimination in both the public and private sectors, ensure privacy
and confidentiality and ethics in research involving human subjects, emphasise
education and conciliation, and provide for speedy and effective administrative and
civil remedies.

6. States should enact legislation to provide for the regulation of HIV-related goods,
services and information, so as to ensure widespread availability of qualitative
prevention measures and services, adequate HIV prevention and care information and
safe and effective medication at an affordable price.

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7. States should implement and support legal support services that will educate people
affected by HIV and AIDS about their rights, provide free legal services to enforce
those rights, develop expertise on HIV-related legal issues and utilise means of
protection in addition to the courts, such as offices of ministries of justice, health
complaint units and human rights commissions.

8. States, in collaboration with and through the community, should promote a


supportive and enabling environment for women, children and other vulnerable
groups by addressing underlying prejudices and inequalities through community
dialogue, specially designed social and health services and support to community
groups.

9. States should promote the wide and ongoing distribution of creative education,
training and media programmes explicitly designed to change attitudes of
discrimination and stigmatisation associated with HIV and AIDS to understanding
and acceptance.

10. States should ensure that government and the private sector develop codes of
conduct regarding HIV and AIDS issues that translate human rights principles into
codes of professional responsibility and practice, with accompanying mechanisms to
implement and enforce these codes.

11. States should ensure monitoring and enforcement mechanisms to guarantee the
protection of HIV-related human rights, including those of people living with HIV
and AIDS, their families and communities.

12. States should co-operate through all relevant programmes and agencies of the
United Nations system, including UNAIDS, to share knowledge and experience
concerning HIV-related human rights issues and should ensure effective mechanisms
to protect human rights in the context of HIV and AIDS at international level.

79
CHAPTER 13
PROGRAMMATIC MONITORING AND EVALUATION

Introduction
The Paediatric ART programme aims to provide universal access to HIV treatment
including antiretroviral therapy to all children in Nigerian that require it. Specifically
it aims to:
• Provide antiretroviral therapy to all eligible children in Nigeria
• Ensure adequate treatment, care and support services to all HIV infected children
who are not eligible for ARV’s
• Build up Capacity within country for the management of children with HIV
infection

13.1 Indicators to track the Paediatric ART programme


The following indicators (Table 13.1) should be used to monitor the Paediatric ART
programme.

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Table 13.1 Paediatric ART Programme Core indicators
Code Indicator Periodicity Source
of
reporting

ART 1 Core 1: Existence of up-to-date Paediatric Annually Informant survey


national policies, strategy, and guidelines for
ART programmes

ART 2 Core 2: Percentage of Local Government Annually Mapping/ listings/


Areas with at least one health facility Health facility
providing Paediatric ART services in-line with survey
national guidelines

ART 3 Core 3: Percentage of health facilities with Biannually Health facility


systems and items to provide Paediatric ART survey
services

ART 4 Core 4: Number of health workers trained on Annually Programme


Paediatric ART delivery in accordance with records,
national standards

ART 5 Core 5: Percentage of ARV storage and Annually Drug tracking


delivery points experiencing stock-outs in the system,
previous 6 months programme
reports

ART 6 Core 6: Percentage of children with advanced Annually Review of


HIV infection receiving ARV combination programme
therapy monitoring data
and estimates

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Code Indicator Periodicity Source
of
reporting

ART 7 Core 7: Number of HIV-infected children Annually ART register


Continuing first-line regimens at 3, 6, 12, 18
and 24 months after initiation

ART 8 Core 8: Number of children surviving at 3, 6, Annually Review of patient


12, 24, 36, etc. months after initiation of registers/Cohort
treatment Analysis Form

ART 9 Functional status of HIV positive children on Annually Review of patient


ART at 6, 12, 24, 36, etc. months after registers/Cohort
initiation of treatment Analysis Form

13.2 Paediatric ART Management Information System (ART MIS)


The objective of the Paediatric ART programme is to reduce HIV and AIDS related
morbidity and mortality in children. The ART Management Information System (ART
MIS) was developed to provide programme level information to guide and improve the
delivery of Paediatric ART services. The information from the ART MIS also will be
used to generate a number of the core indicators that will be calculated at national level
annually.

These programme level information (also called service statistics) are reported on monthly
basis using the monthly summary form and the cohort analysis sheet. Data on these
statistics will be collected by the Data Clerk in accordance with the ART MIS
guidelines. The essential service statistics elements of the Paediatric ART
Programme are listed in Table 13.2

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Table 13.2: Service statistics for Paediatric ART Programme

Indicator Indicator Periodicity of Source


Type reporting

Input Core 1: Existence of up-to-date Annually Informant survey


Paediatric National policies, strategy,
and guidelines for ART programmes

Input Core 2: Percentage of Local Annually Mapping/ listings/


Government Areas with at least one Health facility
health facility providing Paediatric survey
ART services in-line with national
guidelines

Input Core 3: Percentage of health facilities Biannually Health facility


with systems and items to provide survey
Paediatric ART services

Input Core 4: Number of health workers Annually Programme


trained on Paediatric ART delivery in records,
accordance with National Guidelines

Process Core 5: Percentage of ARV storage Annually Drug tracking


and delivery points experiencing system,
stock-outs in the previous 6 months programme
reports

Process Core 6: Percentage of children with Annually Review of


advanced HIV infection receiving programme
ARV combination therapy monitoring data
and estimates

Process Core 7: Number of HIV-infected Annually ART register


children continuing first-line regimens
at 3, 6, 12, 18 and 24 months after
initiation

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Indicator Indicator Periodicity of Source
Type reporting

Outcome Core 8: Number of children surviving Annually Review of patient


at 3, 6, 12, 24, 36, etc. months after registers/Cohort
initiation of treatment Analysis Form

Outcome Functional status of HIV positive Annually Review of patient


children on ART at 6, 12, 24, 36, etc. registers/Cohort
months after initiation of treatment Analysis Form

Impact HIV infection rate in children (%) Biennially National Surveys

Outcome Percentage of children living with Annually Review of patient


HIV and AIDS receiving standard registers/Cohort
ART services returning to schools and Analysis Form
other productive activities after one
year on treatment.

Impact Death rate among children with HIV Annually Review of patient
and AIDS who are on treatment and or registers/Cohort
care (%) Analysis Form

Number of children cumulatively


enrolled into the ART programme for
Output: Monthly Patient registers
HIV care before this reporting period
(month)

Number of children newly enrolled


Output: into the ART programme for HIV care Monthly Pre-ART register
during the last month

Number of children cumulatively


enrolled into the ART programme for
Output: Monthly Pre-ART register
HIV care since the beginning of the
programme

84
Indicator Indicator Periodicity of Source
Type reporting

No of children eligible for ART but


Output: Monthly Pre-ART register
yet to commence ART

Number of children cumulatively


Output: started on ART before this reporting Monthly ART register
period (month)

Number of children newly started on


Output: Monthly ART register
ART during the last month

Number of children cumulatively


Output: started on ART since the beginning of Monthly ART register
the programme

Number of children cumulatively


Output: transferred in for ART from other Monthly ART register
health facilities

Number of children newly transferred


Output: into the ART programme for ART Monthly ART register
from other facilities during the month

Number of children who restarted


Output: ART therapy after stopping therapy Monthly ART register
for more than 3 months

Number of children who did not pick


Output: Monthly ART register
up their ARV regimens in the month
Number of children newly enrolled
Output: for HIV care who were screened for Monthly Pre-ART register
TB this month

Number of children newly enrolled for


Output: HIV care who were placed on INH Monthly Pre-ART register
prophylaxis this month

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Indicator Indicator Periodicity of Source
Type reporting

Number of children newly enrolled for


Output: HIV care who were placed on CTX Monthly Pre-ART register
prophylaxis this month

Number of children currently on 1st-


Output: Monthly ART register
line ART regimen this month

Number of children currently on 2nd


Output: Monthly ART register
line ART regimen this month

Number of children on Salvage drug


Output: Monthly ART register
regimen this month

Number of children newly enrolled for


Output: Monthly ART register
ART who were screened for TB

Number of children who were offered


Output: Monthly PITC Register
PITC

Number (%) of children whose


Output: caregivers accepted to be tested for Monthly PITC Register
HIV

Number (%) of children who tested


Output: Monthly PITC Register
positive for HIV

Number (%) of children who tested


Output: Monthly PITC Register
negative for HIV

13.3 Tools for and methods of monitoring


The ART MIS system includes the following tools:

1. The Care/ART Card

2. PMM forms including:

a. Paediatric clinical evaluation and follow up forms

b. Laboratory request and result forms

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c. Pharmacy order forms

d. Adherence strategy work plan

3. Pre-ART register

4. ART register

5. ART monthly summary forms

6. Cohort analysis forms

13.4 Data flow

At each ART site, the ART monthly summary form should be completed and
forwarded to the Local Government, where the data are collated and in turn forwarded
to the state Ministry of Health. At the state level, all HIV data should be collated,
analyzed and forwarded to the NASCP FMOH (see Figure 13.1).

87
Report flow for HIV/AIDS Health sector Service Provision Data

Federal Ministry of Health


Presidency (NHMIS)
(Presidential Council on AIDS)

National Action Committee Federal Ministry of Health (NASCP)


on AIDS

State Action Committees on AIDS State Ministry of Health


State AIDS Programmes

Local Government Health departments (PHC


LGA (Local Government Action coordinator/ Medical Officer of Health
Committees on AIDS)

1. Primary Health care facilities


2. Private health facilities
3. All health care facilities

National Response Health Sector Response

88
The respective health authorities at the various levels will have responsibility for
reporting to the HIV and AIDS coordinating authorities at the level (i.e. Primary
Health Care coordinator to Local Government Area Action Committee on AIDS; the
State AIDS Programme to the State Action Committees on AIDS; and the National
AIDS and STI control Programme report to the National Agency for the Control of
AIDS.

13.5 Data Analysis and Reporting

Data collected will be analysed at the national level and findings will contribute to
programme planning and implementation. It will also be NACA to fit into the
NNRIMS. The FMOH will design feedback mechanisms to ensure that each level of
service, the management, partners and stakeholders are informed on a quarterly basis
on service statistics of HCT services in the country.

13.6 Project management meeting


The Paediatric HIV Clinical Care Team comprising of the medical officer, pharmacy
staff, adherence counsellors, nurses, record officer, laboratory scientist and
nutritionist, should meet monthly. The essence of this meeting is to share insights,
discuss issues pertaining to patient care and participate in care updates on topics of
interest. During this meeting the service statistics of the previous months should be
shared and discussed to provide insight into the successes and challenges in Paediatric
HIV service delivery and proffer solutions.

89
ANNEX 1: PAEDIATRIC WEIGHT-BASED DOSING CHART

90
ANNEX IIa: Sexual maturity rating (Tanner staging) in female adolescents
Stage Age Breast Breast growth Pubic hair Pubic Hair growth Other
range growth growth changes
(years)
I 0−15 Preadolescent None Preadolescent

II 8−15 Breast budding Long downy Peak growth


(thelarche); pubic hair near the velocity often
areolar hyperplasia labia, often occurs soon after
with small amount appearing with stage
of breast tissue breast budding or
several weeks
or months later
III 10−15 Further Increase in Menarche occurs in
enlargement amount and 2% of girls late in
of breast tissue and pigmentation stage III
areola, with no of hair
separation of their
contours
IV 10−17 Separation of Adult in type Menarche occurs in
contours; areola but not in most girls
and nipple form distribution in stage IV, 1−3
secondary mound years after
above breast tissue thelarche

V 12.5−18 Large breast with Adult in Menarche


single contour distribution occurs in
10% of girls
in stage

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ANNEX IIb. Sexual maturity rating (Tanner staging) in male adolescents

Stage Age range Testicular growth Penile growth Pubic hair External Other
(years) growth appearance changes

I 0−15 Pre-adolescent Preadolescent None Pre-adolescent


testes (≤2.5 cm)

II 10−15 Enlargement of Minimal Long downy hair, Not applicable


testes; or no often appearing
pigmentation of enlargement several months after
scrotal sac testicular growth;
variable pattern noted
with pubarche
III 10.5−16.5 Further Significant Increase in amount; Not applicable
enlargement enlargement, curling
especially in
diameter

IV Variable: Further Further Adult in type but not Development of axillary hair and
12−17 enlargement enlargement, in distribution some facial hair
especially in
diameter

V 13−18 Adult in size Adult in size Adult in distribution Body hair continues to grow and
(medial aspects of muscles continue to increase in
thighs; linea alba) size for several months to years;
20% of boys reach peak growth
velocity during this period.

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