Tukei - 24 Month HIV Free Survival Among HIV Exposed Infants in Lesotho (Cohort)

Tukei VJ et al.
Journal of the International AIDS Society 2020, 23:e25648

http://onlinelibrary.wiley.com/doi/10.1002/jia2.25648/full | https://doi.org/10.1002/jia2.25648
RESEARCH ARTICLE
24-Month HIV-free survival among HIV-exposed Infants in

Lesotho: the PEAWIL cohort study
Vincent J Tukei1,§ , Rhoderick Machekano2, Michelle M Gill2, Appolinaire Tiam2,3, Majoalane Mokone1,
Anthony Isavwa1, Malijane Nyabela1, Tsietso Mots’oane4, Seipati Nchephe4, Mosilinyane Letsie4, Seble G Kassaye5
and Laura Guay2,6
Corresponding author: Vincent J Tukei, LCA Office Complex, 30 Princess Margaret Road, Old Europa, Maseru, Lesotho. Tel: +266 58860881. ([email protected])
§
Abstract
Introduction: Following the implementation of the provision of lifelong antiretroviral therapy to all HIV-positive pregnant or
breastfeeding women for prevention of mother-to-child transmission (PMTCT) of HIV by the Kingdom of Lesotho in 2013, we
assessed the effectiveness of this approach by evaluating 24-month HIV-free survival among HIV-exposed infants (HEIs).
Methods: We conducted a prospective observational cohort study that enrolled HIV-positive and HIV-negative pregnant
women, with follow-up of women and their infants for 24 months after delivery. Participant recruitment started in June 2014
and follow-up ended in September 2018. Trained nurses collected study information through patient interviews and chart
abstraction at enrolment and every three to six months thereafter. Maternal HIV testing, infant mortality, HIV transmission
and HIV-free survival rates were computed using Kaplan–Meier estimation. Cox regression hazard models were used to iden-
tify factors associated with infant HIV infection and death.
Results: Between June 2014 and February 2016, we enrolled 653 HIV-positive and 941 HIV-negative pregnant women.
Twenty-seven HIV-negative women acquired HIV during follow-up. Ultimately, 634 liveborn HEI (382 (52%) male, 303 (48%)
female, 3 missing) and 839 who remained HIV-unexposed (HUIs) (409 (49.0%) male, 426 (51.0%) female, 4 missing) were fol-
lowed; 550 HEIs and 701 HUIs completed the 24-month follow-up period. Of 607 (95.7%) HEIs who were tested for HIV at
least once during follow-up, 17 were found to be HIV-positive. Two (9.5%) of 21 infants born to mothers who acquired HIV
infection during follow-up were HIV-positive compared to 15 (2.4%) of 613 HEI born to women with known HIV infection.
The risk of HIV transmission from HIV-positive mothers to their infants by 24 months of age was 2.9% (95% CI: 1.8 to 4.7).
The estimated 24-month mortality rate among HEIs was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8% (95% CI: 2.6 to 5.3)
among HUIs (Log-rank p = 0.065). HIV-free survival at 24 months was 91.8% (95% CI: 89.2 to 93.7). Lower maternal age and
birth weight were independently associated with increased HIV infection or death of infants.
Conclusions: The implementation of lifelong ART for PMTCT in the Lesotho public health system resulted in low HIV trans-
mission, but survival of HEI remains lower than their HIV uninfected counterparts.
Keywords: human immunodeficiency virus; prevention; mother-to-child-transmission; infant; mortality; Lesotho; HIV-free survival
Received 28 June 2020; Accepted 13 November 2020

Copyright © 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
1 | INTRODUCTION The implementation of these PMTCT strategies has led to

tremendous success in the prevention of new infections
The HIV epidemic in children is largely due to mother-to-child among children [5-7]. In 2013, the World Health Organization
HIV transmission (MTCT). In 2018, the Joint United Nations (WHO) released new guidelines on the use of antiretroviral
Program on HIV/AIDS (UNAIDS), estimated that 160,000 new drugs for the treatment of pregnant women and the preven-
HIV infections occurred among children [1]. Without treat- tion of HIV infection in infants [8]. These guidelines, initially
ment, approximately one-half of HIV-infected children in sub- known as Option B+, recommended lifelong antiretroviral
Saharan Africa die before their second birthday [2,3]. Prevent- therapy (ART) for all pregnant and breastfeeding women with
ing new infections and providing early treatment to infected a six-week administration of daily nevirapine to the infant.
infants are essential strategies for controlling the HIV epi- In settings where this PMTCT strategy is fully implemented,
demic in infants and children [3]. a substantial reduction in new HIV infections has been real-
Over the last two decades, strategies for the prevention of ized. There is clear evidence showing improved HIV-free sur-
mother-to-child HIV transmission (PMTCT) have evolved to vival for infants tested at six weeks of age [9-11]; however,
include maternal use of highly active antiretroviral drugs [4]. there is limited information on the long-term effectiveness of
1
17582652, 2020, 12, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/jia2.25648 by Nat Prov Indonesia, Wiley Online Library on [27/06/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Tukei VJ et al. Journal of the International AIDS Society 2020, 23:e25648
this strategy among breastfeeding populations in high HIV random selection of medium (100 to 200 ANC attendees/
prevalence settings where infants often continue to be year) and high volume (>200 ANC attendees/year) health cen-
exposed to HIV throughout the first two years of life. In tres in the three districts.
2013, the Kingdom of Lesotho, with an HIV prevalence of To be enrolled in the study, pregnant women had to be
25.8% among pregnant women, adopted these WHO guide- attending ANC at a study facility, reside within the facility
lines. catchment area, and be willing to provide written informed
The PMTCT Program Effectiveness among Women and consent. There was no age restriction for study enrolment as
Infants in Lesotho (PEA-WIL) study aimed to evaluate the young pregnant women in Lesotho are considered emanci-
effectiveness of PMTCT service delivery and assess progress pated and therefore provided their own consent for participa-
towards the virtual elimination of mother-to-child HIV trans- tion. Women who temporarily received care from the health
mission (EMTCT) in selected districts of Lesotho [12]. This facility were excluded. Infants were automatically eligible for
paper presents findings on 24-month HIV-free survival among enrolment at birth.
HEI, factors associated with infant HIV infection and death, Infants were considered HIV exposed if their mothers were
and compares survival among HEI and HUI. found to be HIV positive during pregnancy, delivery or during
the breastfeeding period, including infants born to HIV-nega-
tive women who seroconverted during follow-up.
2 | METHODS
2.1 | Study design 2.4 | Study procedures
This was a prospective observational cohort study that involved Study-specific information was obtained at enrolment, around
the recruitment and follow-up of pregnant women attending the time of delivery, and every three months postpartum. Ges-
antenatal care (ANC) clinics at selected health facilities in tational age at enrolment was determined based on the date
Lesotho. We recruited HIV-positive and HIV-negative pregnant of the last menstrual period. Trained study nurses interviewed
women and followed them during pregnancy up to 24 months the women and abstracted additional study information from
postpartum. Infants born to these women were followed along the medical records using structured data collection forms.
with their mothers for the 2-year period after delivery. The nurses reviewed participant medical records and
abstracted information on general health and clinical/labora-
tory history of infants, birth history, hospitalizations, ARV use
2.2 | Study setting
and toxicity, retention in care, infant feeding practices and
During the study period, health facilities provided routine infant growth. Relevant information on deliveries or admis-
PMTCT services to all pregnant women as part of general sions that occurred in non-study facilities, was extracted from
ANC. Pregnant women were offered opt-out HIV screening the participant’s medical booklet upon return to the study
followed by ART initiation if the women tested HIV positive. facility. At every visit, participants were interviewed to assess
HIV-negative women received repeat HIV tests at 36 weeks adherence to ART in the seven days preceding the visits. In
of pregnancy or delivery, and in the postnatal period. Based addition, we conducted study-specific HIV DNA PCR testing
on the national PMTCT guidelines, the preferred ART regimen at birth and at six months, and a final rapid antibody test on
was a fixed-dose combination of tenofovir disoproxil fumarate, all exposed children at 24 months of age.
lamivudine and efavirenz administered once daily. HIV viral HIV-unexposed infants (HUIs) were assessed every three to
load monitoring was carried out every six months, and women six months when their mothers returned to the clinics for
found to have viral load results <1000 copies/mL were consid- postnatal care and HIV re-testing. Women were re-tested
ered virally suppressed. every three months until 12 months postpartum and at 18
HEIs were initiated on daily nevirapine from birth to six and 24 months postpartum. HIV-negative women who sero-
weeks of age and on daily cotrimoxazole from six weeks of converted during follow-up were started on ART and their
age until HIV infection was definitively excluded. Exclusive infants tested for possible HIV infection. At every study visit,
breastfeeding for the first six months of life was encouraged. study nurses collected information on infant feeding practices.
To assess HIV infection in the infant, HIV DNA PCR tests For children who died during follow-up, mortality informa-
were carried out at four and fourteen weeks of infant age. tion was obtained through chart abstraction at the health
Infants with negative DNA PCR results were subsequently re- facilities. Information on date of death, the primary cause of
tested using WHO-recommended rapid antibody tests at nine death and medication given to the child at the time of death
months, with confirmatory DNA PCR testing if positive. was abstracted. For deaths that occurred outside health facili-
Infants with negative HIV test results at nine months, ties, parents or caregivers were interviewed to determine
received a rapid antibody test at 18 months of age or six events at the time of death.
weeks after cessation of breastfeeding. HIV-positive infants
were initiated on ART.
2.5 | Statistical analysis
We summarized maternal and infant characteristics at delivery
2.3 | Study sites and participants
using frequencies and proportions by infant HIV exposure sta-
Between June 2014 and February 2016, we consecutively tus. Continuous variables were summarized using means
enrolled pregnant women from 14 health facilities (five hospi- (SD) or medians (range) by exposure status. We also summa-
tals and nine health centres) located in three of Lesotho’s ten rized and compared 24-month infant outcomes using fre-
districts. These health facilities represented all hospitals and a quencies and proportions with associated 95% confidence
2
intervals. Chi-square tests were used to test for significant dif- (2.9%) stillborn) and 879 HIV unexposed infants (860
ferences between HIV-exposed and -unexposed infants. (97.8%) liveborn, 19 (2.2%) stillborn) (Figure 1). This
For each infant who did not die during follow-up, we calcu- includes eight sets of HEI twins and 11 sets of HUI twins.
lated the time at risk of death from birth to the last follow-up During the postpartum follow-up period, an additional 19
date. For infants who died, their time at risk for death was HIV-negative women with 21 children seroconverted. Alto-
calculated as the difference between date of birth and date of gether, 634 liveborn infants (328 (52.0%) male, 303 (48%)
death. We created an indicator variable for death, with those female, 3 missing) were HIV exposed. 24-month outcomes
who did not die censored at the last known follow-up date. were available for 588 HEI (550 (93.5%) alive and 38
The HIV infection risk time was calculated only among HIV-ex- (6.5%) died) and 733 HUI (701 (95.6%) alive and 32 (4.4%)
posed infants who had at least one HIV test. For infants who died) with 87% of eligible HEI having a 24-month final HIV
were not infected, the time at risk for HIV infection was cal- test done.
culated as the difference between the date of birth and the Overall, 45.5% of mothers was under age 25 years; of the
date of last HIV-negative test. For infants who became 19 women who seroconverted after delivery, 84% was under
infected with HIV, their time at risk for HIV infection was cal- age 25 years (Table 1). The proportion of women who dis-
culated as the difference between the date of birth and the closed their HIV status to someone was 74.4%, with 66.7%
date of the first HIV-positive test. An HIV infection indicator disclosing to their partner/spouse. At delivery, 96.9% of moth-
variable was created with infants who were not infected cen- ers of HIV-exposed infants was on ART (median time on
sored at the last HIV-negative test date. We created an indi- ART = 6.6 months; IQR: 4 to 31.6 months). Of 595 HIV-ex-
cator for HIV-free survival based on either death or HIV posed infants with information on infant antiretroviral prophy-
infection and the HIV-free survival time was calculated as the laxis, 576 (96.8%) were initiated on nevirapine, with the
minimum time between being at risk of death and at risk for majority of infants initiating prophylaxis within the first
HIV infection. 72 hours of life. About 50% of HIV-exposed and unexposed
We estimated infant mortality, MTCT and HIV-free survival infants with information available on breastfeeding practices
rates over time using Kaplan Meier estimation. Kaplan Meier was exclusively breastfed for the first six months of life. Mixed
graphs were used to describe mortality, infection and survival feeding in the first six months of life was reported in 218/551
patterns over time. We used Wilcoxon log-rank tests to com- (39.6%) HIV-exposed infants and 337/705 (47.8%) HIV-unex-
pare the survival curves between HIV-exposed and unexposed posed infants.
infants. During the 24-month follow-up period, 38 (6.0%) HIV-ex-
We estimated the proportion of infants who died or were posed infants died compared to 31 (3.7%) HIV-unexposed
infected by the different categories of maternal and infant infants (chi-square p = 0.039) (Table 2).
characteristics assessed at delivery. We used univariate Cox The diagnosis preceding death is as shown in Table 3
regression to identify factors associated with infant death or below.
HIV infection. Factors that were significantly associated with A total of 607 (95.7%) HIV-exposed infants were tested
infant death or HIV infection in the unadjusted analyses were for HIV at least once during follow-up. Of these, 17 (2.8%)
included in a multivariate Cox regression model to identify were HIV infected. Four of the 17 infants were diagnosed at
independent factors associated with death or HIV infection. birth (in utero infection rate, 0.7%). Two (9.5%) of the 21
The strength of the association was expressed as adjusted infants born to mothers who acquired HIV infection during
hazard ratios and associated 95% confidence intervals. All sta- follow-up were HIV infected compared to 15 (2.4%) of 613
tistical analyses were performed using Stata version 15.1 (Col- HEI tested at birth who were born to women with known
lege Station, TX, USA). HIV infection. All HIV-positive infants were put on ART.
Table 4 shows the estimated mortality, HIV transmission and
HIV-free survival rates over time by exposure status. The
2.6 | Ethical considerations
estimated 24-month mortality rate among HIV-exposed
This study was approved by the Lesotho National Health infants was 6.0% (95% CI: 4.4 to 8.2) compared to 3.8%
Research Ethics Committee, the Baylor College of Medicine (95% CI: 2.6 to 5.3) among HIV-unexposed infants (Log-rank
Children’s Foundation Lesotho Institutional Review Board p = 0.065). The overall estimated risk of HIV transmission
(IRB), and the George Washington University IRB. Written from HIV-positive mothers to their infants was 2.9% (95%
informed consent was obtained from the mothers for their CI: 1.8 to 4.7).
own participation and the participation of their infants. All Figure 2 displays Kaplan–Meier curves of mortality, HIV
study team members were trained on the protection of transmission and HIV-free survival for the infants by HIV
human subjects. exposure status. Mortality is high during the first two months
of life for both HIV-exposed and HIV-unexposed infants but
thereafter, mortality among HEIs is markedly higher than mor-
3 | RESULTS tality in HUIs. The rate of in utero infection was low, 0.7%,
with most infection occurring during the postnatal period
A total of 1594 pregnant women were enrolled in the through age 12 months.
study, of which 653 (41.0%) were HIV positive and 941 In unadjusted models, younger maternal age, lack of viral
(59.0%) were HIV negative. By the time of delivery, eight suppression, lower birth weight, and prematurity were inde-
HIV-negative women had sero-converted to become HIV pendently associated with increased HIV infection or death of
positive. Birth information was available for 631 infants that HEI (Table 5). Marital status, maternal education, disclosure of
were HIV exposed by delivery (613 (97.1%) liveborn, 18 HIV status to someone else or husband, being on ART at
3
Figure 1. Child follow-up and HIV testing from birth to 24 months postpartum. Note: *LTFU = Loss to follow-up;** 1 additional child death
in each group with unknown age at death.
delivery, delivery mode, type of infant feeding, sex of child and of women <25 years of age were more likely to be HIV-posi-
ARV prophylaxis were not associated with the hazard of HIV tive or die compared to children of women ≥25 years (Hazard
infection or death. ratio (HR) = 2.51, 95% CI: 1.29 to 4.87). Among infants born
After model adjustment, however, only maternal age, birth to adolescent and young women (14-24 years), 25 (14.4%)
weight and infant maturity at birth remained independently were infected or died compared to 27 (5.8%) infants born to
associated with HIV infection or death of the infant. Children older women (25 to 45 years).
4
Table 1. Maternal and infant characteristics by child HIV exposure status among liveborn infants
HIV exposed at delivery HIV exposed during follow-up HIV unexposed

Characteristic n (%) n (%) n (%) Total
Characteristics of mothers of liveborn infants

Number of mothers with delivery information 607 19 830 1456
Age at delivery in years median (range) 29 (17 to 45) 21 (15 to 28) 23 (14 to 45) 25 (21 to 31)
Age group (years)
14 to 24 158 (26.2%) 16 (84.2%) 487 (58.7%) 661 (45.5%)
25 to 45 446 (73.8%) 3 (15.8%) 343 (41.3%) 792 (54.5%)
Marital status
Married/living with partner 492 (81.5%) 14 (73.7%) 719 (86.6%) 1225 (84.3)
Never married 70 (11.6%) 4 (21.1%) 106 (12.8%) 180 (12.4)
Divorced/widowed 42 (7.0%) 1 (5.3%) 5 (0.6%) 48 (3.3)
Education
Primary or less 265 (43.9%) 5 (26.3%) 278 (33.5%) 548 (37.7)
Secondary 202 (33.4%) 10 (52.6%) 314 (37.8%) 526 (36.2)
High school 97 (16.1%) 4 (21.1%) 175 (21.1%) 276 (19.0)
Tertiary 40 (6.6%) 0 63 (7.6%) 103 (7.1)
HIV status disclosure (at any time)
Disclosed to someone 518 (85.8%) 11 (57.9%) 552 (66.5%) 1081 (74.4)
No disclosure 86 (14.2%) 8 (42.1%) 278 (33.5%) 372 (25.6)
HIV status disclosure to husband/partner
Disclosed 353 (74.5%) 7 (50.0%) 445 (61.9%) 805 (66.7)
Did not disclose 121 (25.5%) 7 (50.0%) 274 (38.1%) 402 (33.3)
On ART at delivery or during follow-up
Yes 588 (96.9%) 13 (61.9%) NA
No 19 (3.1%) 8 (38.1%)
Delivery mode
Vaginal 511 (84.7%) 13 (68.4%) 717 (86.8%) 1241 (85.7)
Cesarean 92 (15.3%) 6 (31.6%) 109 (13.2%) 207 (14.3)
Viral suppression (during entire follow-up period)
Suppressed (<1000 copies/mL) 358 (60.2%) 3 (25.0%) NA 361 (59.5)
Not suppressed 237 (39.8%) 9 (75.0%) 246 (40.5)
Infant characteristics
Number of live infant births 613 21 839 1473
Sex
Male 314 (51.5%) 14 (66.7%) 409 (49.0%) 737 (50.3%)
Female 296 (48.5%) 7 (33.3%) 426 (51.0%) 729 (49.7%)
Infant feeding in first 6 months
Exclusive breast feeding 279 (52.0%) 6 (40%) 349 (49.5%)
Exclusive alternatives to breast feeding 47 (8.8%) 1 (6.7%) 19 (2.7%)
Mixed feeding 210 (39.2%) 8 (53.3%) 337 (47.8%)
Infant initiated on ARV prophylaxis
Yes 576 (96.8%) NA NA
No 19 (3.2%)
ARV prophylaxis initiated within 72 hours
Yes 560 (94.8%) NA NA
No 31 (5.2%)
Birth weight in kg 3.03 (0.52) 3.02 (0.69) 3.12 (0.53) 3.08 (0.53)
mean (SD)
Birth weight category
<2.5 kg 59 (10.4%) 4 (23.5%) 65 (8.3%) 128 (9.3)
>2.5 kg 511 (89.6%) 13 (76.5%) 718 (91.7%) 1242 (90.7)
5
Table 1. (Continued)
HIV exposed at delivery HIV exposed during follow-up HIV unexposed

Characteristic n (%) n (%) n (%) Total
Infant maturity at birth

Term 568 (93.3%) 20 (100%) 803 (96.6%) 1391 (95.3)
Pre-terma 41 (6.7%) 0 28 (3.4%) 69 (4.7)
a
Preterm = Born alive before 37 completed weeks of gestation.
Table 2. Infant outcomes by final HIV exposure status in the public healthcare setting of Lesotho is 91.8%. These
results demonstrate the effectiveness of universal, lifelong
HIV exposed HIV unexposed p-value ART implemented among breastfeeding communities residing
Outcome N (%) N (%) in a high HIV-prevalence setting, and are consistent with find-
ings of a similar study conducted in urban Kigali, Rwanda
Total live births 634 839 between 2013 and 2016 in which Gill et al reported a 24-
Died 38 (6.0%) 31 (3.7%) 0.039 month HIV transmission of 2.2% and an HIV-free survival rate
HIV infected 17/607 (2.8%) 0 –
of 93.2% [7].
Several studies conducted within sub-Saharan Africa have
Died or HIV infected 52 (8.2%) 31 (3.7%) <0.001
assessed HIV-free survival up to six weeks of infant age [9-
HIV-free survivala 581 (91.8%) 806 (96.3%)
11,13]. Outcomes at six weeks of infant age reflect the trans-
a
HIV-free survival could not be determined for 3 infants (1 HEI and 2 mission that occurs during pregnancy and the peripartum per-
HUI) with missing data iod but fail to show the outcomes of continued HIV exposure
that occurs during the breastfeeding period. In many sub-
Saharan African settings, women breastfeed their babies
Table 3. Diagnosis preceding death of infants during follow-up throughout the first year of life and often through the second
year [13]. The results of our study are noteworthy since they
HIV exposed HIV unexposed cover the entire breastfeeding period and take into considera-
Diagnosis infants infants Total tion the diverse infant feeding practices. Mixed feeding,
though practised by a number of women in our cohort, was
Acute respiratory tract 7 5 12 not associated with HIV transmission. A community-based
infection cohort study conducted in rural Zambia reported an HIV-free
Diarrhoea and vomiting 5 2 7 survival of 96.3% at 12 months of infant age, slightly higher
Neonatal sepsis 5 2 7 than found in this study [15]. In Zimbabwe, serial cross-sec-
Birth asphyxia 2 8 10 tional community-based sero-surveys that evaluated the
PMTCT effectiveness at nine to eighteen months of infant
Severe acute 2 0 2
age, showed a 10% MTCT rate and HIV-free survival of
malnutrition
89.6% in 2012, with a 2014 repeat survey showing a reduc-
Congenital 1 1 2
tion in MTCT to 4.8% and an increase in HIV-free survival to
abnormalities 95.1% with the WHO Option A PMTCT strategy [16].
Foreign body aspiration 1 1 2 For PMTCT programmes to be effective in reducing infec-
Vitamin K deficiency 1 0 1 tion and death among infants, a “cascade” of PMTCT services
bleeding needs to be effectively delivered and accessed during antena-
Accidental drowning 0 1 1 tal care, delivery, and in the postnatal period. These services
Intestinal obstruction 0 2 2 include mother and partner HIV testing and counselling, and if
Unknown 14 9 23 HIV positive, initiation and retention on ART; prompt initiation
Total 38 31 69 of antiretroviral prophylaxis for the HEI once born, and infant
HIV testing at six weeks of age and subsequent time points if
HIV negative until six weeks after discontinuation of breast-
For every 100-gram increase in birth weight, the risk of feeding [17,18]. In addition, prevention counselling and repeat
HIV infection or death in infants decreased by 7% (HR = 0.93, tests need to be carried out on HIV-negative mothers with
95% CI: 0.86 to 0.99); and preterm infants had a higher risk immediate initiation of ART whenever HIV is diagnosed and
of infection or death compared to term infants (HR = 3.11, testing of the child if breastfed.
95% CI 1.12 to 8.65). Due to challenges in the healthcare system in many sub-
Saharan African countries like Lesotho, these proven interven-
tions are seldom fully implemented. In many settings, only a
4 | DISCUSSION proportion of women receives ANC at health facilities and
these services are often sought late in pregnancy or at deliv-
Our results show that mother-to-child transmission of HIV by ery [19]. The results reported here clearly demonstrate that
24 months of age is 2.9% and HIV-free survival among HEIs the implementation of universal maternal ART markedly
6
Table 4. Estimated child mortality, infection and HIV-free survival rates by HIV exposure status among liveborn infants
Mortality rate HIV-Free Survival rate Survival rate
HIV exposed HIV unexposed HIV transmission rate HIV exposed HIV unexposed
Time % [95% CI] % [95% CI] % [95% CI] % [95% CI] % [95% CI]
6 weeks 2.4 [1.5 to 4.0] 2.7 [1.8 to 4.1] 0.6 [0.3 to 1.8] 96.8 [95.1 to 97.9] 97.3 [95.9 to 98.2]
6 months 4.1 [2.8 to 6.0] 3.3 [2.3 to 4.8] 1.9 [1.0 to 3.4] 94.5 [92.3 to 96.0] 96.7 [95.2 to 97.7]
Log rank p 0.065 – <0.001
Figure 2. Kaplan-Meier graphs of child mortality, HIV transmission and HIV-free survival by HIV exposure status among liveborn infants.
reduces MTCT even in non-ideal public health settings where breastfeeding markedly increases the risk of MTCT of HIV
ANC and postnatal services are suboptimal. [23-26]. We found that HIV transmission was four times
For the HEI, prevention of HIV transmission from the higher in HIV-negative women who seroconverted compared
mother largely depends on the mother’s ability and willing- to women who were HIV positive at delivery. This under-
ness to initiate and continue with lifelong ART and on her scores the need for additional protections for HIV negative
adherence to treatment to maintain sustained virological sup- women during pregnancy and the breastfeeding period. Nev-
pression. When mothers do not adhere to treatment or ertheless, the majority of the transmissions still occurred
become lost to follow-up, treatment interruptions occur that among women who were known to be HIV positive at enrol-
lead to an increase in the risk of HIV transmission to the ment. The suboptimal viral suppression seen in some of
infant [20-22]. In addition, HIV-negative mothers who acquire these women may have contributed to the transmission.
infection during pregnancy risk transmitting the virus to their Although not assessed, viral resistance to ART may have led
infants. Acute HIV infection during pregnancy or to the observed viraemia.
7
Table 5. Maternal and infant factors associated with infant’s HIV infection or death in exposed infants (N = 634)
Characteristic Total (n) Infected or died, n (%) Unadjusted HR [95% CI] Adjusted HR [95% CI] p-value
Maternal characteristics
Mother’s age (years)
14 to 24 174 25 (14.4%) 2.53 [1.45 to 4.44] 2.51 [1.29 to 4.87] 0.007
25 to 45 448 26 (5.8%) 1 1
Marital status
Married/living with partner 505 38 (7.5%) 1
Never married 74 10 (13.5%) 1.75 [0.85 to 3.64]
Divorced/widowed 43 3 (7.0%) 0.94 [0.29 to 3.04]
Education
Primary or less 269 26 (9.7%) 1
Secondary 212 15 (7.1%) 0.69 [0.36 to 1.33]
High school 101 8 (7.9%) 0.81 [0.37 to 1.81]
Tertiary 40 2 (5.0%) 0.54 [0.13 to 2.28]
HIV status disclosure
Disclosed to someone 528 39 (7.4%) 1
No disclosure 94 12 (12.8%) 1.89 [0.99 to 3.63]
Disclosure to husband/partner
Disclosed 400 27 (6.8%) 1 1
Did not disclose 222 24 (10.8%) 1.71 [0.98 to 3.0]
On ART at delivery
Yes 587 43 (7.3%) 1
No 18 3 (16.7%) 1.21 [0.17 to 8.79]
Viral suppression
Suppressed 361 19 (5.3%) 1 1
Not Suppressed 245 25 (10.2%) 2.05 [1.13 to 3.73] 1.81 [0.92 to 3.56] 0.089
Delivery mode
Vaginal 524 39 (7.4%) 1
Cesarean 98 10 (10.2%) 1.36 [0.68 to 2.72]
Infant characteristics
Sex
Male 324 19 (5.9%) 1 0.08
Female 297 29 (9.8%) 1.68 [0.94 to 2.99]
Infant feeding in first 6 months of life
Exclusive breast feeding 280 19 (6.8%) 1
Exclusive formula feeding 47 1 (2.1%) 0.29 [0.04 to 2.17]
Mixed feeding 216 10 (4.6%) 0.62 [0.29 to 1.34]
Initiated ARV prophylaxis
Yes 569 35 (6.2%) –
No 19 0
ARV prophylaxis within 72 hours
Yes 554 34 (6.1%) 1
No 30 1 (3.3%) 0.53 [0.07 to 3.84]
Birth weight (per 100 grams increase) 567 37 0.88 [0.84 to 0.92] 0.93 [0.86 to 0.99] 0.04
Maturity at birth
Term 581 39 (6.7%) 1 1
Preterma 39 10 (25.6%) 4.21 [2.10 to 8.42] 3.11 [1.12 to 8.65] 0.03
a
Preterm = Born alive before 37 completed weeks of gestation.
The significantly lower survival of HEIs compared to HUIs uninfected (HEU) children. These HEU infants and children
in this study draws attention to the continued need for early have in previous studies been found to have impaired growth
diagnosis followed by prompt initiation of ART for all HIV-pos- and higher infectious disease morbidity than their HIV-unex-
itive children and close follow-up of all HIV-exposed posed counterparts [27-29]. The underlying mechanisms
8
leading to worse adverse outcomes in these group of HEI are address the additional vulnerabilities encountered by infants
not fully known, but are likely to be a combination of several of adolescent and young women.
factors including intrauterine growth retardation and preterm
birth, seen more often among HIV-exposed newborns [30], AUTHORS’ AFFILIATIONS
immune dysfunction [31] and other adverse environmental 1
Elizabeth Glaser Pediatric AIDS Foundation, Maseru, Lesotho; 2Elizabeth Gla-
and socio-economic conditions. ser Pediatric AIDS Foundation, Washington, DC, USA; 3Centre for International
Another important finding is the observed association Health, University of Bergen, Norway; 4Ministry of Health, Maseru, Lesotho;
5
between maternal age and HIV infection or death in infants. Department of Medicine, Georgetown University School of Medicine, Washing-
ton, DC, USA; 6Department of Epidemiology, George Washington University
A significantly higher proportion of infants born to adoles- Milken Institute School of Public Health, Washington, DC, USA
cent or young women was infected or died compared to the
deaths or infections seen in infants of older women. As the COMPETING INTERESTS
universal ART programme in Lesotho continues to mature,
The authors do not have any competing interests.
there is a need to explore the underlying factors contributing
to the negative PMTCT outcomes seen among adolescent
girls and young women. A large study in Zimbabwe found AUTHORS’ CONTRIBUTIONS
that adolescent pregnant women were less likely to know Funding acquisition: AT, MGG, AI, SGK, LG. Conceptualization and initial proto-
their HIV status or be on ART prior to ANC attendance, col development: RM, MGG, AT, AI, MN, MT, SN, ML, SGK and LG. Protocol
revisions and refinement of data collection tools: VT, RM, MGG, AT, MM, MN,
which could be one of the contributing factors [32]. To MT, SN, SGK and LG. Investigation: VT, RM, MGG, AT, AI, MN, MT, SN, ML,
improve child survival, there is a need to reinforce current SGK and LG. Project administration and Data Collection: VT, RM, MGG, AT,
MCH and PMTCT efforts with appropriate interventions that MM, SGK and LG. Supervision: VT, RM, MGG, AT, MM, MT, SN, ML, SGK and
take into consideration the increased vulnerabilities seen LG. Drafting the manuscript: VT. Review and editing of manuscript: VT, RM,
MGG, AT, MM, AI, MN, MT, SN, ML, SGK and LG.
among these young mothers. In addition, these results high-
light the need to strengthen sexual and reproductive health
services for young women to prevent HIV acquisition and ACKNOWLEDGEMENTS
pregnancy. We thank the study participants for their time and commitment during the
Our study had some limitations. We were only able to implementation of this study. We thank the staff at the participating facilities,
the Christian Health Association of Lesotho (CHAL) and the Lesotho Ministry of
assess HIV-free survival among infants born to women who Health for their support during data collection and participant follow-up. We
attended ANC services at health facilities. It is likely that acknowledge the contribution of Dr. Justine Mirembe, Mr. Ian Membe and other
some pregnant women did not attend ANC or delivered at staff at the USAID office in Lesotho, whose dedication and commitment made
home without visiting the facilities leading to an underestima- this study possible.
tion of our study outcomes. We are therefore unable to esti-
mate HIV-free survival at the population level. In addition, FUNDING
children who were lost to follow-up may have been infected This work was made possible by the generous support of the American people
or died leading to underestimation of these outcomes. Infor- through the President’s Emergency Plan for AIDS Relief and the United States
mation on diagnoses preceding death of infants was, in some Agency for International Development.
cases, obtained from caregivers through phone interviews or
abstracted from patient records at the health facilities. The DISCLAIMER
accuracy of abstracted data depended on the information The results described here were made possible by the Unites States Agency for
recorded by the clinicians who saw the patients. It is possible International Development (USAID) and the generous support of the American
people through USAID Cooperative Agreements AID-674-A-15-00008 and AID-
that some of the diagnoses were inaccurate. Post-mortem
674-A-16-00005. The contents included here are the responsibility of the
examination of deceased infants was not conducted, making it authors and do not necessarily represent the official views of USAID.
difficult to determine the cause of death. A number of women
had suboptimal viral suppression and our data on adherence
to ART had gaps and quality issues. We were unable to use it REFERENCES
in this analysis, and this may have limited our understanding 1. UNAIDS. Global HIV and AIDS Statistics - 2019 Fact Sheet. 2019 [cited
of the reasons for the high viral load seen. Despite these limi- 2020 Jun 4]. Available from: https://www.unaids.org/en/resources/fact-sheet
tations, our study provides promising results of PMTCT imple- 2. Marston M, Becquet R, Zaba B, Moulton LH, Gray G, Coovadia H, et al. Net
survival of perinatally and postnatally HIV-infected children: a pooled analysis of
mentation from a region with the highest HIV prevalence in
individual data from sub-Saharan Africa. Int J Epidemiol. 2011;40(2):385–96.
the world. 3. Newell ML, Coovadia H, Cortina-Borja M, Rollins N, Gaillard P, Dabis F, et al.
Mortality of infected and uninfected infants born to HIV-infected mothers in
Africa: a pooled analysis. Lancet. 2004;364(9441):1236–43.
5 | CONCLUSIONS 4. Tsague L, Abrams EJ. Commentary: antiretroviral treatment for pregnant and
breastfeeding women–the shifting paradigm. AIDS. 2014;28 Suppl 2:S119–21.
5. Townsend CL, Byrne L, Cortina-Borja M, Thorne C, de Ruiter A, Lyall H,
The implementation of universal ART in the Lesotho’s public et al. Earlier initiation of ART and further decline in mother-to-child HIV trans-
health system has markedly reduced HIV MTCT rates that mission rates, 2000–2011. AIDS. 2014;28(7):1049–57.
approached the global target of <2%. However, despite access 6. Tang Q, Liu M, Lu H. Prevention of mother-to-child transmission (PMTCT)
continues to play a vital role in the response to HIV/AIDS: Current status and
to ART, HIV-positive children still had lower survival than
future perspectives. Biosci Trends. 2019;13(1):107–9.
their HIV-negative counterparts, as did HIV exposed but unin- 7. Gill MM, Hoffman HJ, Ndatimana D, Mugwaneza P, Guay L, Ndayisaba GF,
fected children. The results here provide additional evidence et al. 24-month HIV-free survival among infants born to HIV-positive women
on the effectiveness of current PMTCT strategies and under- enrolled in Option B+ program in Kigali, Rwanda: the Kabeho Study. Medicine.
score the need for differentiated PMTCT interventions that 2017;96:e9445.
9
8. WHO. Consolidated guidelines on the use of antiretroviral drugs for treating 20. Decker S, Rempis E, Schnack A, Braun V, Rubaihayo J, Busingye P, et al.
and preventing HIV infection. Recommendations for a public health approach. Prevention of mother-to-child transmission of HIV: Postpartum adherence to
Geneva, Switzerland: WHO Press; 2013. [cited 2019 February 24]. Available Option B+ until 18 months in Western Uganda. PLoS One. 2017;12:e0179448.
from: http://www.who.int/hiv/pub/guidelines/arv2013/download/en/ 21. Scott GB, Brogly SB, Muenz D, Stek AM, Read JS. Missed opportunities for
9. Kadima N, Baldeh T, Thin K, Thabane L, Mbuagbaw L. Evaluation of non- prevention of mother-to-child transmission of human immunodeficiency virus.
adherence to anti-retroviral therapy, the associated factors and infant outcomes Obstet Gynecol. 2017;129(4):621–8.
among HIV-positive pregnant women: a prospective cohort study in Lesotho. 22. Woldesenbet S, Jackson D, Lombard C, Dinh TH, Puren A, Sherman G,
Pan Afr Med J. 2018;30:239. et al. Missed opportunities along the prevention of mother-to-child transmission
10. Mugwaneza P, Lyambabaje A, Umubyeyi A, Humuza J, Tsague L, Mwa- services cascade in south africa: uptake, determinants, and attributable risk (the
nyumba F, et al. Impact of maternal ART on mother-to-child transmission SAPMTCTE). PLoS One. 2015;10:e0132425.
(MTCT) of HIV at six weeks postpartum in Rwanda. BMC Public Health. 23. Birkhead GS, Pulver WP, Warren BL, Hackel S, Rodriguez D, Smith L.
2018;18(1):1248. Acquiring human immunodeficiency virus during pregnancy and mother-to-child
11. Tippett Barr BA, van Lettow M, van Oosterhout JJ, Landes M, Shiraishi RW, transmission in New York: 2002–2006. Obstet Gynecol. 2010;115(6):1247–55.
Amene E, et al. National estimates and risk factors associated with early 24. Seidman DL, Weber S, Cohan D. Offering pre-exposure prophylaxis for HIV
mother-to-child transmission of HIV after implementation of option B+: a cross- prevention to pregnant and postpartum women: a clinical approach. J Int AIDS
sectional analysis. Lancet HIV. 2018;5(12):e688–95. Soc. 2017;20 Suppl 1:21295.
12. Tiam A, Gill MM, Hoffman HJ, Isavwa A, Mokone M, Foso M, et al. Conven- 25. Drake AL, Wagner A, Richardson B, John-Stewart G. Incident HIV during
tional early infant diagnosis in Lesotho from specimen collection to results usage pregnancy and postpartum and risk of mother-to-child HIV transmission: a sys-
to manage patients: Where are the bottlenecks? PLoS One. 2017;12:e0184769. tematic review and meta-analysis. PLoS Med. 2014;11:e1001608.
13. Sherman GG, Mazanderani AH, Barron P, Bhardwaj S, Niit R, Okobi M, 26. Machekano R, Tiam A, Kassaye S, Tukei V, Gill M, Mohai F, et al. HIV inci-
et al. Toward elimination of mother-to-child transmission of HIV in South Africa: dence among pregnant and postpartum women in a high prevalence setting.
how best to monitor early infant infections within the Prevention of Mother-to- PLoS One. 2018;13:e0209782.
Child Transmission Program. J Glob Health. 2017;7(1):10701. 27. Brennan AT, Bonawitz R, Gill CJ, Thea DM, Kleinman M, Long L, et al. A
14. Hunegnaw MT, Gelaye KA, Ali BM. Factors associated with the time to ces- Meta-analysis assessing diarrhea and pneumonia in HIV-exposed uninfected
sation of breastfeeding among mothers who have index children aged two to compared with HIV-unexposed uninfected infants and Children. J Acquir
three years in Debre Markos, northwest Ethiopia: a retrospective follow up Immune Defic Syndr. 2019;82(1):1–8.
study. BMC Pediatr. 2018;18(1):77. 28. le Roux SM, Abrams EJ, Donald KA, Brittain K, Phillips TK, Zerbe A, et al.
15. Chi BH, Mutale W, Winston J, Phiri W, Price JT, Mwiche A, et al. Infant Infectious morbidity of breastfed, HIV-exposed uninfected infants under condi-
human immunodeficiency virus-free survival in the era of universal antiretroviral tions of universal antiretroviral therapy in South Africa: a prospective cohort
therapy for pregnant and breastfeeding women: a community-based cohort study. Lancet Child Adolesc Health. 2020;4(3):220–31.
study from Rural Zambia. Pediatr Infect Dis J. 2018;37(11):1137–41. 29. Koyanagi A, Humphrey JH, Ntozini R, Nathoo K, Moulton LH, Iliff P, et al.
16. Buzdugan R, Kang Dufour MS, McCoy SI, Watadzaushe C, Dirawo J, Mush- Morbidity among human immunodeficiency virus-exposed but uninfected, human
avi A, et al. Option A improved HIV-free infant survival and mother to child HIV immunodeficiency virus-infected, and human immunodeficiency virus-unexposed
transmission at 9–18 months in Zimbabwe. AIDS. 2016;30(10):1655–62. infants in Zimbabwe before availability of highly active antiretroviral therapy.
17. Luzuriaga K, Mofenson LM. Challenges in the elimination of pediatric HIV-1 Pediatr Infect Dis J. 2011;30(1):45–51.
infection. N Engl J Med. 2016;374(8):761–70. 30. Xiao PL, Zhou YB, Chen Y, Yang MX, Song XX, Shi Y, et al. Association
18. Barker PM, Mphatswe W, Rollins N. Antiretroviral drugs in the cupboard between maternal HIV infection and low birth weight and prematurity: a meta-
are not enough: the impact of health systems’ performance on mother-to-child analysis of cohort studies. BMC Pregnancy Childbirth. 2015;15:246.
transmission of HIV. J Acquir Immune Defic Syndr. 2011;56(2):e45–8. 31. Abu-Raya B, Kollmann TR, Marchant A, MacGillivray DM. The Immune Sys-
19. UNAIDS. 2015 Progress Report on the Global Plan Towards the Elimina- tem of HIV-Exposed Uninfected Infants. Front Immunol. 2016;7:383.
tion of New HIV Infections among Children and Keeping their Mothers Alive. 32. Musarandega R, Machekano R, Chideme M, Muchuchuti C, Mushavi A,
Geneva, Switzerland: Joint United Nations Program on HIV/AIDS; 2015. https:// Mahomva A, et al. PMTCT service uptake among adolescents and adult women
www.unaids.org/sites/default/files/media_asset/JC2774_2015ProgressReport_ attending antenatal care in selected health facilities in Zimbabwe. J Acquir
GlobalPlan_en.pdf Immune Defic Syndr. 2017;75(2):148–55.
10

Tukei - 24 Month HIV Free Survival Among HIV Exposed Infants in Lesotho (Cohort)

Uploaded by

Copyright:

Available Formats

Tukei - 24 Month HIV Free Survival Among HIV Exposed Infants in Lesotho (Cohort)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Tukei - 24 Month HIV Free Survival Among HIV Exposed Infants in Lesotho (Cohort)

Uploaded by

Copyright:

Available Formats

Tukei VJ et al.

Journal of the International AIDS Society 2020, 23:e25648

24-Month HIV-free survival among HIV-exposed Infants in

Received 28 June 2020; Accepted 13 November 2020

1 | INTRODUCTION The implementation of these PMTCT strategies has led to

HIV exposed at delivery HIV exposed during follow-up HIV unexposed

Characteristics of mothers of liveborn infants

HIV exposed at delivery HIV exposed during follow-up HIV unexposed

Infant maturity at birth

Mortality rate HIV-Free Survival rate Survival rate

You might also like