Hirnschall G et al.

Journal of the International AIDS Society 2013, 16:18757

http://www.jiasociety.org/index.php/jias/article/view/18757 | http://dx.doi.org/10.7448/IAS.16.1.18757

Commentary

The next generation of the World Health Organization’s global

antiretroviral guidance
Gottfried Hirnschall1, Anthony D Harries2,3, Philippa J Easterbrook§,1, Meg C Doherty1 and Andrew Ball1
§
Corresponding author: Philippa J Easterbrook, HIV Department, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland. Tel:  41 22 791 21 11.
([email protected])

Abstract
The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and
preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including
recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment
services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age
groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are
based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus
on resource-limited settings.
The most important new clinical recommendations include: treating adults, adolescents and older children earlier
starting
ART in all individuals with a CD4 cell count of 500 cells/mm3 or less (but giving priority to those with advanced clinical disease or
a CD4 cell count less than 350 cells/mm3); starting ART at any CD4 cell count in certain populations, including those with active
TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV-positive partners in serodiscordant
couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred
first-line ART regimen of Tenofovir3TC or FTC Efavirenz as a once-daily fixed-dose combination for adults, pregnant women,
and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to
ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services,
including strategies to improve retention in care, and adherence to ART; task-shifting to address human resource gaps;
decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug
dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources
most efficiently.
Keywords: ARV guidelines; WHO; adults; pregnant women; adolescents; children.
Received 24 May 2013; Revised 17 June 2013; Accepted 17 June 2013; Published 30 June 2013
Copyright: – 2013 Hirnschall G et al; licensee International AIDS Society. This is an open access article distributed under the terms of the Creative Commons
Attribution 3.0 Unported (CC BY 3.0) Licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.

Introduction and history represents 65% of the global target of 15 million on ART
A core function of the World Health Organization (WHO) HIV by 2015 set by the UN General Assembly in 2011, and an
programme is to translate new evidence, experience and increase of 1.6 million from the end of 2011 [11,12]. This
technical innovations into global guidance to inform scale increased ART access has been associated with declining HIV
up of national antiretroviral (ARV) programmes. In 2002, mortality and incidence rates in several countries. The global
WHO first published guidelines on the use of antiretroviral target of 15 million on ART by 2015 is now within reach [13],
therapy (ART) among adults and adolescents [1], and in 2001 and a few countries (including resource-limited countries)
and 2004, on ARV use for the prevention of mother-to-child have already reached or are close to achieving ‘‘universal
transmission (PMTCT) of HIV [2,3]. The 2006 and 2010 access’’ to ART (defined as greater than 80% coverage of
updates of these guidelines [4
9] used the concept of a those eligible for ART).
public health approach, with simplified ART regimens, and in However, several major challenges will need to be over-
2010, the CD4 threshold for ART initiation was raised from come if progress towards universal access is to be sustained.
5200 cells/mm3 to 5350 cells/mm3 [9]. This has facilitated ART coverage is highly variable across countries, ages and
impressive progress in the global scale up of ART. By the end populations [8,9]. In particular, the levels of ART coverage
of 2011, the majority of 80 low- and middle-income countries for children (younger than 15 years) and pregnant women
(LMICs) included in a survey had adopted the 2010 CD4 eligible for ART for their own health are considerably lower
initiation threshold of less than 350 cells/mm3 in their than those for other adults [12]. Treatment access is also
national guidelines [10]. At the end of 2012, an estimated low in settings where the epidemic is concentrated among
9.7 million people in LMICs were receiving ART. This marginalized populations, such as sex workers, people who

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Hirnschall G et al. Journal of the International AIDS Society 2013, 16:18757
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inject drugs, and men who have sex with men [12]. The and prevention and management of drug interactions. Third,
majority of people living with HIV in LMICs are unaware in addition to the updated clinical recommendations, there is
of their HIV status [14]. In addition, late presentation is operational guidance on how to implement ARV programmes
common, so ART is only initiated when disease is advanced more efficiently and improve ART access, with recommen-
and CD4 cell counts are well below the recommended dations on task shifting, decentralization, integration and
threshold, resulting in a high risk of early mortality [12]. adherence. Furthermore, there is programmatic guidance on
Finally, there is still a high attrition rate at all stages along the how to support the translation of clinical and operational
continuum of care [15]. recommendations into policy and practice at national level,
including what parameters to consider when setting priorities
Why new consolidated guidelines? and deciding on the implementation of the recommenda-
Since the 2010 guidelines, a series of landmark studies tions. Fourth, new recommendations on the use of ARVs
have provided new evidence on the individual clinical for treatment and prevention are harmonized with links to
and HIV prevention benefits of earlier ART [16
19]. This has the existing WHO guidance on other major aspects of HIV
led to new WHO guidance on its use for HIV prevention diagnosis, ARV-related prevention, and HIV care and treat-
in serodiscordant couples [20], PMTCT [21], prevention of ment. Finally, there is guidance on proposed indicators for
TB [22] and pre-exposure prophylaxis (PrEP) of HIV [23]. monitoring implementation of new recommendations and
In addition, once-daily, fixed-dose combination ARV regimens programme performance across the continuum of care.
for use in most populations and age groups have become more
widely available and affordable in LMICs, and new testing The guidelines development process
approaches and technologies, including CD4 point-of-care The revision process for the 2013 guidelines was initiated in
assays, have enabled increasing decentralization of HIV testing early 2012, and conducted in accordance with procedures
and care.
established by the WHO Guidelines Review Committee [25].
As the HIV treatment and prevention benefits of ARVs
Clinical and operational recommendations were developed
become clearer, HIV programme managers are faced with a
using the GRADE system (Grading of Recommendations,
broadening array of options for their use in reducing HIV
Assessment, Development and Evaluation), which empha-
morbidity, mortality and transmission in different popula-
sizes a structured, explicit and transparent approach to rating
tions. Using ARVs most strategically requires careful decision
the quality of evidence and strength of recommendations
making at the clinical, operational and programmatic levels.
[26]. The decision-making process involved a critical review of
For example, changes are needed in service delivery models
to support timely initiation of ART, optimal treatment ad- the evidence based mainly on systematic reviews of rando-
herence and retention in care across the continuum of care. mized clinical trials and, where appropriate, observational
In response to these advances, WHO has now updated and studies. The process was further complemented by consid-
combined all its ARV-related guidance into one consolidated eration and assessment of costs and resource implications,
guidelines document: Consolidated guidelines on the use impact and cost-effectiveness modelling based on potential
of antiretroviral drugs for treating and preventing HIV recommendations, feasibility of and barriers to implementa-
infection [24]. The primary target audience is national tion, surveys of community and health worker values and
programme managers who make policy and planning deci- preferences, and equity and human rights implications. These
sions in settings with limited health system capacity and were all considered to inform the weighing up of benefits
resources, but it also includes agencies that provide financial and harms of potential recommendations.
and technical support to HIV programmes, clinicians and As in the past, the implementation of the guidelines and
other health service providers. The guidance addresses the scale up of ARV use are underpinned by several key guiding
clinical, operational and programmatic aspects of using principles. The first principle is a public health approach that
ARV drugs for both HIV treatment and prevention across all seeks to ensure the widest possible access to high-quality
age groups and populations, and across the entire continuum services at the population level, balancing the best evidence-
of care. based standard of care with the feasibility of large-scale
implementation in resource-limited settings. Second is the
What is different about the consolidated core principle of human rights and health equity to guide
guidelines? national HIV policies and programmes, and so ensure that
First, instead of separate ARV guidelines for adults (including among those eligible for ART, priority is given to those most
pregnant women) and children, all age groups and populations in need, and that care is provided in an environment that
are now covered, enabling a more harmonized approach to the minimizes stigma and discrimination. The third guiding
choice of ARV regimens and treatment approaches. Second, principle is optimizing the effectiveness and efficiency of
the clinical guidelines adopt a continuum of care approach HIV programmes across the continuum of care through a
from diagnosis of HIV to the use of ARVs in prevention, pre-ART strategic mix of HIV testing approaches, improved adherence
care, initiation and maintenance of first-, second- and third- and retention measures, innovative service delivery models,
line ART regimens, monitoring for treatment failure and ARV harmonized drug regimens, and simpler and more affordable
toxicity, management of co-infections and co-morbidities, point-of-care diagnostics and laboratory services.

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Table 1. Comparison of key WHO recommendations on when to start ART and choice of drug regimen between 2010 and 2013 as
well as operational recommendations

When to initiate ART (ARV-naive individuals)

Population Target population 2010 ART guidelines 2013 ART guidelines

Adults and HIV-infected individuals CD4 cell count 5350 cells/mm3 CD4 cell count 5500 cells/mm3
adolescents* or or
WHO clinical stage 3 or 4 regardless WHO clinical stage 3 or 4 regardless
of CD4 cell count of CD4 cell count
3
HIV-infected pregnant and CD4 cell count 5350 cells/mm regardless Regardless of CD4 cell count or WHO
breastfeeding women of clinical symptoms clinical stage
or
WHO clinical stage 3 or 4 regardless of
CD4 cell count

HIV-infected partners in No recommendation established Regardless of CD4 cell count or WHO

serodiscordant couple clinical stage [20]
relationship(s)
HIV/TB co-infection Presence of active TB disease, regardless of No change
CD4 cell count
HIV/HBV co-infection Evidence of chronic active HBV disease, Evidence of chronic HBV disease with
regardless of CD4 cell count severe liver disease (e.g., cirrhosis),
regardless of CD4 cell count
3
Children HIV-infected children ]5 years CD4 cell count 5350 cells/mm CD4 cell count 5500 cells/mm3
old or or
WHO clinical stage 3 or 4 regardless of WHO clinical stage 3 or 4 regardless
CD4 cell count of CD4 cell count
HIV-infected children 1
5 years 1. Between 12 and 24 months of age, Regardless of CD4 cell count and
old regardless of CD4 cell count or WHO clinical WHO clinical stage
stage.
2. Between 24 and 59 months of age with
CD4 cell count of 5750 cells/mm3 or CD4%
525, or whichever is lower, regardless of WHO
clinical stage.

HIV-infected infants B1 year old All infants, regardless of CD4 cell count No change
and WHO clinical stage

What ART regimen to start with (ARV-naive individuals)

Adults and HIV-infected individuals AZT or TDF3TC (or FTC)EFV or NVP

adolescents* HIV-infected pregnant and AZT3TCNVP or EFV
breastfeeding ARV-naive TDF3TC (or FTC)EFV
women (as a fixed-dose combination)
HIV/TB co-infection AZT or TDF3TC (or FTC)EFV
HIV/HBV co-infection TDF3TC (or FTC)EFV
Adolescents* Weighing B35 kg ABC (or AZT or TDF)3TCEFV
Children ]3 years old NVP or EFV2 NRTI [AZT/3TC (preferred)] ABC (or AZT or TDF)3TCEFV
B3 years old** NVP2 NRTI [AZT/3TC (preferred)] ABC (or AZT)3TCLPV/r
(regardless of PMTCT exposure)

*Adolescents are defined as aged 10 to 19 years inclusive.

**In children less than 2 years of age, previously exposed to NNRTIs, the use of a LPV/r based treatment was recommended.

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Key changes in the 2013 guidelines and to achieve the global goal of eliminating new paedia-
Table 1 summarizes the key clinical recommendations on tric infections, WHO recommends ART in one simplified
when and what to start in the 2013 guidelines and how they regimen to all pregnant and breastfeeding women regardless
differ from those in 2010. of CD4 cell count during the period of risk of mother-to-child
transmission (MTCT).
Earlier initiation of ART (CD4 cell countsB500 cells/mm3) Continuation of life-long ART regardless of CD4 cell count
The new recommendations include expanding eligibility for or clinical status (Option B  ) is recommended, particularly
ART initiation to a CD4 threshold of 500 cells/mm3 or less in generalized epidemic settings with high rates of fertility,
for adults, adolescents and children (five years and older), and limited access to CD4 testing. Option B was first
while prioritizing those in greatest need: those with ad-
proposed and implemented in Malawi, and it provides
vanced HIV disease or CD4 cell counts of 350 cells/mm3 or
important programmatic and clinical benefits [29], including
less. The recommendation for earlier ART initiation at a CD4
harmonization of the ARV regimen with that used in non-
cell count between 350 and 500 cells/mm3 is supported by
pregnant adults, ease of implementation (women who are
moderate-quality evidence of reduced morbidity and mor-
tality from a systematic review of 21 observational studies immune compromised can start ART straightaway without
and 3 randomized controlled trials [27], high-quality evidence waiting for a CD4 cell count), and avoidance of stopping and
of reduced HIV transmission from one randomized trial [16], starting drugs with repeat pregnancies and so provide early
and cost-effectiveness models that showed that expanding protection against MTCT in future pregnancies. Earlier ART
ART eligibility to 5500 cells/mm3 may result in substantial may also reduce the high post-partum mortality, as well as
health benefits and be cost effective in most epidemic offer protection from HIV transmission to the partner or
settings [28]. spouse [16].
In addition, no studies suggested individual-level harms The 2013 recommendation is conditional, recognizing the
from earlier ART initiation, although these studies were current lack of conclusive evidence to support a universal
generally of limited duration. ART initiation regardless of ART strategy. Countries will have to weigh the benefits of
CD4 cell count is also recommended for certain populations, continuing ARVs after the transmission risk is removed, and
namely pregnant women, HIV-positive partners in serodiscor- may opt for stopping ART after the breastfeeding period
dant couples, children younger than five years of age, those (Option B). Option A is no longer recommended.
with active TB disease, as well as HIV and hepatitis B virus
co-infected individuals with evidence of severe chronic liver Harmonization of ART regimens across populations
disease. There was insufficient evidence and/or favourable The 2013 guidelines promote further simplification of ART
benefit
risk profiles to recommend initiating ART at CD4 cell delivery by recommending a once-daily fixed-dose combina-
counts over 500 cells/mm3 or regardless of CD4 cell count tion of tenofovir, lamivudine or emtricitabine and efavirenz
or WHO clinical stage in the following populations: in all adults as the preferred first-line ART regimen for use across all
and children above 5 years; key populations that are populations of children (older than three years), adolescents,
disproportionately affected by HIV (including men who have adults, pregnant women and women of reproductive ages. In
sex with men, transgender people, people who inject drugs, children less than 3 years of age, a lopinavir-based regimen is
and sex workers); HIV-infected individuals who are 50 years recommended as first-line ART, regardless of NNRTI expo-
of age and older; and those who are co-infected with HIV-2 sure. The recommendations for second-line regimens in 2013
or hepatitis C. The initiation of ART in these people should remain unchanged since 2010, with heat-stable fixed-dose
follow the same general principles and recommendations combinations, and atazanavir/ritonavir and lopinavir/ritona-
as for other adults and adolescents with HIV. Comprehen- vir as the preferred boosted protease inhibitor (PI) options.
sive WHO guidelines on management of hepatitis C will be However, WHO may include darunavir/ritonavir as an alter-
published in 2013.
native PI option should there be a reduction in cost and
Initiating life-long ART in pregnant women a heat-stable fixed-dose combination tablet developed.
In 2010, the WHO guidelines recommended life-long ART The need to phase out stavudine in first-line ART regimens
for pregnant women based on the 2010 eligibility criteria of a for adults and adolescents is further reinforced.
CD4 cell count of 350 cells/mm3 or less, and two complex
Improved patient monitoring with viral load
prophylaxis options (Option A and Option B) for those not yet
Viral load testing is recommended as the preferred approach
eligible for ART. Option A provided twice-daily zidovudine to
the mother from 14 weeks of gestation to the onset of for monitoring ART response to provide an early and more
labour, and single-dose nevirapine and twice-daily zidovudine accurate indication of treatment failure and more appropriate
and lamivudine given for seven days post-partum. Option B switching to second-line drugs, reducing the accumulation of
provided triple ARV therapy to the mother until delivery or if drug-resistance mutations, and improving clinical outcomes.
breastfeeding was continued until one week after all infant A pooled analysis showed the current WHO immunological
exposure to breast milk had ended. Both prophylaxis options and clinical criteria for treatment failure have poor sensitivity
included four to six weeks of peripartum nevirapine prophy- and positive predictive value for identifying virological failure
laxis given to the infants. in adults and children [30]. A systematic review of five
In 2013, in order to accelerate rapid global scale up of randomized controlled trials and one observational study
ART and PMTCT, to increase ART access for pregnant women, provides further support for virological monitoring [31].

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Task shifting, decentralization and integration HIV develop non-communicable diseases (NCDs) related
Treating many more people requires more efficient, accepta- to HIV itself, ageing or ARV complications, closer links
ble and accessible health services. New operational recom- between HIV services and other NCD health services become
mendations emphasize decentralizing ART to primary health increasingly important.
care services and integrating ART provision within TB,
antenatal care, maternal and child health services, and What are the required global investments and
drug-dependence services. The operational guidance also estimated impact?
addresses the implications of new clinical recommendations Estimates in 2011 indicated that an effective global HIV
for laboratory services and drug and diagnostics supply response (including treatment provision based on the
management. 2010 guidelines) would cost US$22
24 billion annually in
2015 [32]. If fully implemented, the 2013 guidelines would
What are the key messages for HIV programme increase the number of people eligible for ART globally to
managers? 25.8 million (compared with 16.7 million under the 2010
National programme managers play a unique role in mana- guidelines). Assuming that ART coverage increases gradually
ging the process of adapting and implementing the global to around 80% of the total number of people eligible for ART,
recommendations for use at country level, and the program- the estimated annual cost of reaching these numbers in 2025
matic guidance offers steps to ensure fair, inclusive and would be an increase of about 10%, or US$2
4 billion per
transparent decision-making processes. In all settings, the year (in addition to the current US$22
24 billion for a
priority should be to treat those people who are in greatest comprehensive HIV response). It is projected that the re-
need of ART for their own health. Further expansion of source needs would level off over time and even start to
ART access and the trajectory towards the implementation of decline after 2025, reflecting the accumulated prevention
other recommendations may involve various policy combina-
benefits of expanded ART provision. If the recommendations
tions depending on the local context. Factors to be con-
are fully implemented, it is projected that by 2025, the
sidered include HIV epidemiology, current ART coverage,
annual mortality would fall from 1.3 to 0.8 million, and 3.5
availability of resources and anticipated cost effectiveness,
million additional new HIV infections would be prevented
and the capacity of the health system. The aim is to achieve
[12]. Changing the eligibility criteria is rated as cost effective,
full implementation of the recommendations as rapidly and
with the cost per quality-adjusted life year saved less
efficiently as possible, ensuring quality, sustainability and
than US$600 and less than US$5000 per new HIV infection
maximum impact of programmes.
Ultimately, the process of guideline revision and adapta- averted.
tion is the responsibility of national stakeholders. Different Estimating impact and costs associated with the imple-
approaches may be necessary and equally valid depending on mentation of new recommendations is a key step in the roll-
the context. Each country will have to plan its own approach out process at country level. As the impact of changes in
to ensure that the current ARV programmes are scaled the eligibility criteria will differ from country to country,
up and sustained, and that expanded access is fair and several online costing tools and resources (Spectrum and
equitable. Finally, countries will also have to align their OneHealth [33]) have been developed to help countries
HIV priorities with their broader health and development model the impact that increasing ART access is likely to have
strategies. on mortality, HIV incidence as well as associated costs, and
are highlighted in the programmatic guidance.
What are the country-level implications of these
guidelines? What comes next?
If treatment scale up is to be sustained, this will require Implementing the 2013 guidelines represents an important
further reductions in ARV drug costs, as well as continued step towards the goal of achieving universal access to HIV
efficiencies and innovations in service delivery. These include prevention and treatment [12], as well as increasing the
simplified HIV diagnostic and laboratory processes (point-of- efficiency, impact and long-term sustainability of ARV pro-
care and dried blood spot technologies, low-cost rapid tests, grammes. In the longer term, the guidelines will also
and well-planned supply chain management), linking decen- contribute to and inform efforts to achieve universal health
tralized approaches with task shifting, and requisite training coverage, a key pillar of the post-2015 development agenda.
and supervision of health staff. While such efforts to increase The 2013 guidelines process also identified key gaps in
efficiency and reduce costs are important, a balance will have knowledge and priority areas for operational and implemen-
to be struck so that quality is not compromised. Improv- tation research and for inclusion in the 2015 update.
ing long-term patient retention and treatment adherence These include: evaluating the impact of earlier ART initiation
through strengthened linkages along the continuum of care, on patient acceptability, adherence, retention, incidence
better ARV formulations (especially for infants and young of toxicities and treatment failure in different populations,
children) and future strategies (sustained-release once- especially pregnant women; the impact of the new service
a-week/month regimens), and a reliable supply chain for delivery models of integration and decentralization; estab-
drugs and diagnostics will also be critical for limiting the lishing optimal short- and long-term approaches for monitor-
further spread of drug resistance. Finally, as HIV increasingly ing ART response and toxicities; and management of key
becomes a chronic manageable condition and people with co-morbidities, including NCDs.

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HIV treatment and care continues to evolve rapidly, 7. Antiretroviral drugs for treating pregnant women and preventing HIV
infection in infants: towards universal access: recommendations for a public
and the guidelines will be comprehensively reviewed and
health approach. 2010 revision. Geneva: World Health Organization; 2010
updated regularly as new evidence emerges and practice [cited 2013 May 17]. Available from: http://whqlibdoc.who.int/publications/
evolves in the use of ARV drugs. When necessary, rapid 2010/9789241599818_eng.pdf
guidance and technical and programmatic updates will 8. Antiretroviral therapy for HIV infection in infants and children: towards
complement the biannual updates. WHO headquarters universal access. Recommendations for a public health approach. 2010
revision. Geneva: World Health Organization; 2010 [cited 2013 May 17].
will work closely with regional and country offices and Available from: http://whqlibdoc.who.int/publications/2010/9789241599801_
implementing partners to ensure wide dissemination of the eng.pdf
updates through regional and sub-regional meetings. 9. Antiretroviral therapy for HIV infection in adults and adolescents:
recommendations for a public health approach. 2010 revision. Geneva: World
Authors’ affiliations Health Organization; 2010 [cited 2013 May 17]. Available from: http://
1
HIV Department, World Health Organization, Geneva, Switzerland; 2International whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf
Union Against Tuberculosis and Lung Disease, Paris, France; 3London School of 10. Gupta S, Granich R, Suthar AB, Smyth C, Baggaley R, Sculier D, et al. Global
Hygiene and Tropical Medicine, London, UK policy review of ART eligibility criteria for treatment and prevention of HIV
and TB in adults, pregnant women, and serodiscordant couples: ART recom-
Competing interests mendations by national guidelines. J Acquir Immune Defic Syndr. 2013;62(3):
The authors participated in the development of the guidelines. GH, PJE, MCD e87
e97.
and AB are staff members of the HIV Department of the WHO. 11. Global HIV/AIDS response: epidemic update and health sector progress
towards universal access: progress report 2011. Geneva: World Health
Authors’ contributions Organization; 2011 [cited 2013 May 17]. Available from: http://whqlibdoc.
PJE wrote the first draft. All authors contributed to revising and commenting who.int/publications/2011/9789241502986_eng.pdf
on subsequent drafts, and approved the final manuscript. 12. Global update on HIV treatment: results, impact and opportunities.
Geneva: World Health Organization; 2013. [cited 2013 June 30]. Availabe
Acknowledgements
from: http://www.who.int/hiv/pub/treatmentupdate2013/
The authors acknowledge the excellent contributions of all members of the
13. United Nations General Assembly. Political declaration on HIV/AIDS:
Guidelines Development Group (GDG), and in particular the co-chairs of the
intensifying our efforts to eliminate HIV and AIDS
United Nations General
four GDGs: Adult: Serge Eholie (ANEPA/Treichville Hospital, Abidjan, Côte
Assembly Resolution 65/277. New York: United Nations; 2011.
d’Ivoire) and Stefano Vella (Istituto Superiore di Sanità, Italy); Maternal and
14. Staveteig S, Wang S, Head SK, Bradley SEK, Nybro E. Demographic patterns
Child Health: Elaine Abrams (International Center for AIDS Care and Treatment
of HIV testing uptake in sub-Saharan Africa. DHS Comparative Reports No 30.
Programs, Mailman School of Public Health, Columbia University, USA) and
Calverton: ICF International; 2013.
Denis Tindyebwa (African Network for the Care of Children Affected by
15. Ware NC, Wyatt MA, Geng EH, Kaaya SF, Agbaji OO, Muyindike WR, et al.
AIDS, Uganda); Operational and Service Delivery: Kevin De Cock (United States
Toward an understanding of disengagement from HIV treatment and care in
Centers for Disease Control and Prevention, USA) and Yogan Pillay (National
sub-Saharan Africa: a qualitative study. PLoS Med. 2013;10(1):e1001369.
Department of Health, South Africa); Programmatic: Adeeba Kamarulzaman
16. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,
(University of Malaya, Malaysia) and Tsitsi Apollo (Ministry of Health and
Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral
Child Welfare, Zimbabwe). The WHO facilitators of the GDGs were: Marco
therapy. N Engl J Med. 2011;365:493
505.
Vitoria (Adults); Nathan Shaffer and Lulu Muhe (Maternal and Child Health); 17. Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, et al.
Eyrusalem Negussie (Operational); and Jos Perriens (Programmatic). Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N
All GRADE tables and summary documents will be available in a
Engl J Med. 2010;363(3):257
65.
webannex (http://www.who.int/hiv/pub/guidelines/arv2013/annexes/) by 18. When To Start Consortium. Timing of initiation of antiretroviral therapy in
September 2013. AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort
studies. Lancet. 2009;373(9672):1352
63.
References 19. Walensky RP, Wolf LL, Wood R, Fofana MO, Freedberg KA, Martinson NA,
1. Scaling up antiretroviral therapy in resource-limited settings. Guidelines for et al. When to start antiretroviral therapy in resource-limited settings. Ann
a public health approach. Geneva: World Health Organization; 2002 [cited 2013 Intern Med. 2009;151(3):157
66.
May 17]. Available from: http://www.who.int/hiv/pub/prev_care/ScalingUp_E. 20. Guidance on couples HIV testing and counseling including antiretroviral
pdf therapy for treatment and prevention in serodiscordant couples: recommen-
2. Prevention of mother-to-child transmission of HIV: selection and use of dations for a public health approach. Geneva: World Health Organization; 2012
nevirapine. Technical notes, 28 February 2001 [cited 2013 May 17]. Available [cited 2013 May 17]. Available from: http://whqlibdoc.who.int/publications/
from: http://www.who.int/hiv/pub/mtct/nevirapine/en/index.html 2012/9789241501972_eng.pdf
3. Antiretroviral drugs for treating pregnant women and preventing HIV 21. Use of antiretroviral drugs for treating pregnant women and preventing
infection in infants. Guidelines on care, treatment and support for women HIV infection in infants: programmatic update. Geneva: World Health
living with HIV/AIDS and their children in resource-constrained settings. Organization; 2012 [cited 2013 May 17]. Available from: http://www.who.
Geneva: World Health Organization; 2004 [cited 2013 May 17]. Available int/hiv/pub/mtct/programmatic_update2012/en/index.html
from: http://www.who.int/hiv/pub/mtct/en/arvdrugswomenguidelinesfinal. 22. WHO policy on collaborative TB/HIV activities: guidelines for national
pdf programmes and stakeholders. Geneva: World Health Organization; 2012 [cited
4. Antiretroviral therapy for HIV infection in adults and adolescents: 2013 May 17]. Available from: http://whqlibdoc.who.int/publications/2012/
recommendations for a public health approach. 2006 revision. Geneva: World 9789241503006_eng.pdf
Health Organization; 2006 [cited 2013 May 17]. Available from: http://www. 23. Guidance on oral pre-exposure prophylaxis (PrEP) for serodiscordant
who.int/hiv/pub/guidelines/artadultguidelines.pdf couples, men and transgender women who have sex with men at high risk
5. Antiretroviral drugs for treating pregnant women and preventing HIV of HIV: recommendations for use in the context of demonstration projects.
infection in infants: towards universal access: recommendations for a public Geneva: World Health Organization; 2012 [cited 2013 May 15]. Available from:
health approach. 2006 revision. Geneva: World Health Organization; 2006 http://apps.who.int/iris/bitstream/10665/75188/1/9789241503884_eng.pdf
[cited 2013 May 17]. Available from: http://www.who.int/hiv/pub/mtct/ 24. Consolidated Guidelines on the use of antiretroviral drugs for treating and
antiretroviral/en/index.html preventing HIV Infection. Geneva: World Health Organization; 2013. Available
6. Antiretroviral therapy of HIV infection in infants and children: towards from: www.who.int/hiv/pub/guidelines/arv2013
universal access. Recommendations for a public health approach. 2006 25. WHO handbook for guideline development. Geneva: World Health
revision. Geneva: World Health Organization; 2006 [cited 2013 May 17]. Organization; 2012 [cited 2013 May 17]. Available from: http://www.who.
Available from: http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf int/kms/guidelines_review_committee/en

6
Hirnschall G et al. Journal of the International AIDS Society 2013, 16:18757
http://www.jiasociety.org/index.php/jias/article/view/18757 | http://dx.doi.org/10.7448/IAS.16.1.18757

26. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. antiretroviral therapy (ART): a systematic review of the performance
GRADE guidelines. 3. Rating the quality of evidence introduction. J Clin characteristics of the 2010 World Health Organization (WHO) immunologic
Epidemiol. 2011;64:401
6. and clinical criteria for virologic failure. Abstract no. TUPE 269. 7th IAS
27. Anglemyer AT, Rutherford GW, Easterbrook PJ, Horvath T, Vitoria M, Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur,
Doherty M. Early initiation of antiretroviral therapy (ART) for individuals with Malaysia; 2013.
HIV infection: a systematic review. Abstract no. TUPE 302. 7th IAS Conference 31. Tucker JD, Bien C, Easterbrook PJ, Penazzato M, Doherty M, Victoria M,
on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, Malaysia; 2013. et al. Optimal monitoring strategies for HIV-infected individuals on antire-
28. Eaton JW, Menzies NA, Stover J, Cambiano V, Chindelevitch L, Cori A, et al. troviral therapy: a systematic review. Abstract no. WEPE 615. 7th IAS
How should HIV programmes respond to evidence for the benefits of earlier Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur,
treatment initiation? A combined analysis of twelve mathematical models.
Malaysia; 2013.
Lancet. 2013 Available from: http://www.hivmodelling.org.
32. Schwartlander B, Sotver J, Hallett T, Atun R, Avila C, Gouws E, et al.
29. Schouten EJ, Jahn A, Midiani D, Makombe SD, Mnthambala A, Chirwa Z,
Towards an improved investment approach for an effective response to HIV/
et al. Prevention of mother-to-child transmission of HIV and the health-related
AIDS. Lancet. 2011;377:2031
41.
millennium development goals: time for a public health approach. Lancet.
33. Futures Institute [Internet]. Glastonbury, CT: Futures Institute; 2013 [cited
2011;378:282
4.
2013 May 15]. Available from: http://www.futuresinstitute.org
30. Rutherford GW, Anglemyer AT, Easterbrook PJ, Horvath T, Vitoria M,
Penazzato M, et al. Predicting treatment failure (TF) in patients on