Facilitators and barriers to antiretroviral therapy adherence among HIV-positive adolescents living in Tanzania.

BACKGROUND: Adolescents living with HIV face substandard outcomes along the continuum of care, including higher rates of poor adherence and virologic failure. Support groups have been identified as a method to improve adherence, but there is insufficient evidence regarding their effectiveness. This study seeks to examine the protective influences for and barriers to antiretroviral therapy (ART) adherence in HIV-positive adolescents living in Tanzania. METHODS: This is a qualitative study conducted in Tanzania from January to March 2018. The sample of adolescents aged 10-19 (n = 33) was purposefully selected based on age, gender, and support group attendance to capture a broad range of experiences. Participants completed an in-depth interview, covering topics such as retention in HIV services, support group experiences, and joys and challenges of adolescent life. Interviews were coded and themes related to ART adherence were identified and summarized. RESULTS: Support groups helped promote adherence by improving adolescents' knowledge and confidence. Participants associated joining support groups with an improvement in health. Almost every participant described the significant positive influence a treatment supporter had on adherence. Adolescents' daily schedules and emotional state served as a barrier to adherence. Furthermore, adherence was negatively impacted by participants' fear of accidental disclosure. CONCLUSION: Logistical and psychosocial factors can hinder adherence. Interventions that provide both education and psychosocial support, such as peer support groups, have the potential to improve health outcomes for this population, but may not address more persistent barriers to adherence rooted in lack of treatment support from family members or friends who have not been disclosed to, or lack of transportation funds/food security.

Mother-to-Child Transmission of HIV and HIV-Free Survival in Swaziland: A Community-Based Household Survey.

In Swaziland, no data are available on the rates of HIV infection and HIV-free survival among children at the end of the breastfeeding period. We performed a national crosssectional community survey of children born 18-24 months prior to the study, in randomly selected constituencies in all 4 administrative regions of Swaziland, from April to June 2015. Mother-to-child transmission (MTCT) of HIV and HIV-free survival rates were calculated for all HIV-exposed children. The overall HIV-free survival rate at 18-24 months was 95.9% (95% CI 94.1-97.2). The estimated proportion of HIV infected children among known HIV-exposed children was 3.6% (95% CI 2.4-5.2). Older maternal age, delivering at a health facility, and receiving antenatal antiretroviral drugs were independently associated with reduced risk for child infection or death. The Swaziland program for prevention of MTCT achieved high HIV-free survival (95.9%) and low MTCT (3.6%) rates at 18-24 months of age when Option A (infant prophylaxis) of the WHO 2010 guidelines was implemented.

Access to HIV prevention and care for HIV-exposed and HIV-infected children: a qualitative study in rural and urban Mozambique.

BACKGROUND: Follow-up of HIV-exposed children for the delivery of prevention of mother-to-child transmission services and for early diagnosis and treatment of HIV infection is critical to their survival. Despite efforts, uptake of postnatal care for these children remains low in many sub-Saharan African countries. METHODS: A qualitative study was conducted in three provinces in Mozambique to identify motivators and barriers to improve uptake of and retention in HIV prevention, care and treatment services for HIV-exposed and HIV-infected children. Participant recommendations were also gathered. Individual interviews (n = 79) and focus group discussions (n = 32) were conducted with parents/caregivers, grandmothers, community leaders and health care workers. Using a socioecological framework, the main themes identified were organized into multiple spheres of influence, specifically at the individual, interpersonal, institutional, community and policy levels. RESULTS: Study participants reported factors such as seeking care outside of the conventional health system and disbelief in test results as barriers to use of HIV services. Other key barriers included fear of disclosure at the interpersonal level and poor patient flow and long waiting time at the institutional level. Key facilitators for accessing care included having hope for children's future, symptomatic illness in children, and the belief that health facilities were the appropriate places to get care. CONCLUSIONS: The results suggest that individual-level factors are critical drivers that influence the health-seeking behavior of caregivers of HIV-exposed and HIV-infected children in Mozambique. Noted strategies are to provide more information and awareness on the benefits of early pediatric testing and treatment with positive messages that incorporate success stories, to reach more pregnant women and mother-child pairs postpartum, and to provide counseling during tracing visits. Increasing uptake and retention may be achieved by improving patient flow at the institutional level at health facilities, by addressing concerns with family decision makers, and by working with community leaders to support the uptake of services for HIV-exposed children for essential preventive care.

Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. METHODS: In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. FINDINGS: Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3-1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3-3·6) of controls (difference 1·3%, 95% CI 0-2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3%vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. INTERPRETATION: Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age. FUNDING: US National Institutes of Health.

Protocol to implement a syndromic surveillance survey of COVID-19 in Malawi.

Introduction: Malawi experienced two waves of COVID-19 between April 2020 and February 2021. A High negative impact of COVID-19 was experienced in the second wave, with increased hospital admissions that overwhelmed the healthcare system. This paper describes a protocol to implement a telephone-based syndromic surveillance system to assist public health leaders in the guidance, implementation, and evaluation of programs and policies for COVID-19 prevention and control in Malawi. Study design: This is a serial cross-sectional telephonic-based national survey focusing on the general population and People living with HIV and AIDS. Methods: We will conduct a serial cross-sectional telephone survey to assess self-reported recent and current experience of influenza-like illness (ILI)/COVID-19-like-illness (CLI), household deaths, access to routine health services, and knowledge related to COVID-19. Structured questionnaires will be administered to two populations: 1) the general population and 2) people living with HIV (PLHIV) on antiretroviral therapy (ART) at EGPAF-supported health facilities. Electronic data collection forms using secure tablets will be used based on randomly selected mobile numbers from electronic medical records (EMR) for PLHIV. We will use random digit dialing (RDD) for the general population to generate phone numbers to dial respondents. The technique uses computer-generated random numbers, using the 10-digit basic structure of mobile phone numbers for the two existing mobile phone companies in Malawi. Interviews will be conducted only with respondents that will verbally consent. A near real-time online dashboard will be developed to help visualize the data and share results with key policymakers. Conclusion: The designed syndromic surveillance system is low-cost and feasible to implement under COVID-19 restrictions, with no physical contact with respondents and limited movement of the study teams and communities. The system will allow estimation proportions of those reporting ILI/CLI among the general population and PLHIV on ART and monitor trends over time to detect locations with possible COVID-19 transmission. Reported household deaths in Malawi, access to health services, and COVID-19 knowledge will be monitored to assess the burden and impact on communities in Malawi.

A randomized controlled trial evaluating the effects of a family-centered HIV care model on viral suppression and retention in care of HIV-positive children in Eswatini.

INTRODUCTION: A family-centered care model (FCCM) providing family-based HIV services, rather than separate adult/pediatric services, has been proposed to increase pediatric retention and treatment adherence. MATERIALS AND METHODS: Eight health-care facilities in the Hhohho region of Eswatini were randomized to implement FCCM (n = 4) or continue standard-of-care (SOC) separate adult/pediatric clinics (n = 4). HIV-positive children and caregivers were enrolled; caregiver interview and child/caregiver chart abstraction were done at enrollment and every three months; pediatric viral load was evaluated at enrollment and every six months through 12 months. Because of study group differences in 12-month viral load data availability (89.4% FCCM and 72.0% SOC children had 12-month viral load), we used three separate analyses to evaluate the effects of FCCM on children's viral suppression (<1,000 copies/mL) and undetectable virus (<400 copies/mL) at 12 months. In the first analysis, all children with missing viral outcome data were excluded from the analysis (modified intent to treat, mITT). The second analysis used inverse probability of missingness weighted logistic regression to estimate the effect of FCCM on 12-month viral outcomes compared to SOC (weighted mITT). For the third approach, missing virologic outcome data were imputed as virologic failure (imputed ITT). We also examined factors associated with viral suppression at 12 months using multivariable logistic regression. RESULTS: We enrolled 379 HIV-positive children and 363 caregivers. Among all children at enrollment, viral suppression and undetectability was 78.4% and 73.9%, respectively, improving to 90.2% and 87.3% at 12 months. In mITT and weighted mITT analyses, there was no significant difference in children's 12-month viral suppression between FCCM and SOC groups (89.2% and 91.6%, respectively). Using imputed ITT, there was a modest increase in 12-month viral suppression in FCCM versus SOC children (79.7% and 69.8%, respectively, p = 0.051) and 12-month undetectability (78.7% and 65.7%, respectively, p = 0.015). Among the 255 children suppressed at enrollment, more FCCM versus SOC children (98.0% versus 95.3%) were suppressed at 12-months, but this was not statistically significant in mITT or weighted mITT analyses, with a marginally significant difference using imputed mITT analysis (p = 0.042). A higher proportion of children suppressed at enrollment had undetectable viral load at 12 months in FCCM versus SOC children (98.0% versus 92.5%), a statistically significant difference across analytical methods. Among the 61 children unsuppressed at enrollment, achieving suppression was higher among SOC versus FCCM children, but this difference was not statistically significant and included only 38 children; and there were no significant differences in detectable viral load at 12 months. There were no significant differences between study groups in retention or ART adherence at 12 months for children or caregivers. Factors associated with lack of viral suppression/detectability at 12 months included lack of viral suppression at enrollment and having a younger caregiver (age <25 years). CONCLUSIONS: FCCM in Eswatini was associated with a modest increase in viral suppression/undetectability at 12-months; 12-month retention and adherence did not differ by study group for children or caregivers. High levels of suppression and retention in both groups may have limited our ability to detect a difference. TRIAL REGISTRATION: NCT03397420; ClinicalTrials.gov.

Adverse Pregnancy Outcomes Among HIV-positive Women in the Era of Universal Antiretroviral Therapy Remain Elevated Compared With HIV-negative Women.

BACKGROUND: Without treatment, HIV infection in pregnant women is associated with adverse pregnancy outcomes. We compared adverse pregnancy outcomes among HIV-positive women on antiretroviral therapy (ART) and HIV-negative women who enrolled for antenatal care in selected health facilities in Maseru district, Lesotho. METHODS: We enrolled a cohort of HIV-positive and HIV-negative women at their first antenatal visit and followed them through delivery. Study data on miscarriage, stillbirth, preterm birth, low birth weight and birth defects were collected through participant interviews and medical record abstraction. We used the Rao-Scott χ2 test and the t test to assess differences in characteristics and outcomes between HIV-positive and HIV-negative women and generalized estimating equations for multivariable analysis. RESULTS: A total of 614 HIV-positive and 390 HIV-negative pregnant women were enrolled in the study with delivery information on 571 (93.1%) and 352 (90.3%) respectively. In the delivery cohort, the median age at enrolment was 28 years for HIV-positive women and 23 years for HIV-negative women with median gestational ages of 20 and 21 weeks, respectively. A total of 149 singleton pregnancies had documented adverse pregnancy outcomes; 33 (9.6%) HIV-negative pregnancies and 116 (20.6%) HIV-positive pregnancies. Compared with their HIV-negative counterparts, HIV-positive women were more likely to experience an adverse pregnancy outcome, adjusted odds ratio (AOR) 2.6 [95% confidence interval (CI): 1.71-3.97]; an intrauterine death (miscarriage or stillbirth), AOR 2.64 [95% CI: 1.25-5.49]; or a low birth weight delivery, AOR 1.89 [95% CI: 1.16-3.09]. CONCLUSION: Adverse pregnancy outcomes remained 2-3 times higher among HIV-positive women compared with HIV-negative women despite universal ART.

Fostering successful and sustainable collaborations to advance implementation science: the adolescent HIV prevention and treatment implementation science alliance.

INTRODUCTION: HIV continues to devastate the adolescent population in sub-Saharan Africa (SSA). The complex array of interpersonal, social, structural and system-level obstacles specific to adolescents have slowed progress in prevention and treatment of HIV in this population. The field of implementation science holds promise for addressing these challenges. DISCUSSION: There is growing consensus that enhanced interactions between researchers and users of scientific evidence are important and necessary to tackle enduring barriers to implementation. In 2017, the Fogarty International Center launched the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) to promote communication and catalyse collaboration among implementation scientists and implementers to enhance the cross-fertilization of insights as research advances and the implementation environment evolves. This network has identified key implementation science questions for adolescent HIV, assessed how members' research is addressing them, and is currently conducting a concept mapping exercise to more systematically identify implementation research priorities. In addition, AHSA pinpointed common challenges to addressing these questions and discussed their collective capacity to conduct implementation science using the shared learning approach of the network. Specifically, AHISA addresses challenges related to capacity building, developing mentorship, engaging stakeholders, and involving adolescents through support for training efforts and funding region-/country-specific networks that respond to local issues and increase implementation science capacity across SSA. CONCLUSIONS: Innovative platforms, like AHISA, that foster collaborations between implementation science researchers, policymakers and community participants to prioritizes research needs and identify and address implementation challenges can speed the translation of effective HIV interventions to benefit adolescent health.

Active pediatric HIV case finding in Kenya and Uganda: A look at missed opportunities along the prevention of mother-to-child transmission of HIV (PMTCT) cascade.

BACKGROUND: Children living with HIV remain undiagnosed due to missed opportunities along the prevention of mother-to-child HIV transmission cascade. This study addresses programmatic gaps in the cascade by describing pregnancy and HIV-related services received by mothers of children newly identified as HIV-positive through active case finding. METHODS: This was a prospective observational cohort (2017-2018) of HIV-positive children <15 years of age newly diagnosed at study facilities and/or surrounding communities in Kenya and Uganda. At enrollment, caregivers were interviewed about maternal and child health and HIV history. Child medical and laboratory information was abstracted at two months post-diagnosis. Descriptive summary statistics were calculated; associations between selected factors and child age at HIV diagnosis were evaluated using generalized estimating equations. RESULTS: 174 HIV-positive children (median age 2.4 years) were enrolled. Among maternal caregivers, 110/132 (83.3%) attended antenatal care and 60 (45.5%) reported testing HIV-negative in antenatal care. Of 41 and 56 women known to be HIV-positive during pregnancy and breastfeeding respectively, 17 (41.5%) and 15 (26.8%) did not receive antiretroviral drugs. Despite known maternal HIV-positive status during pregnancy, 39% of these children were not diagnosed until after two years of age; children were diagnosed at younger ages in Uganda (p = 0.0074) and if mother was the caregiver (p<0.0001). The most common HIV testing points identifying children were outpatient (44.3%) and maternal/child health departments (29.9%). Nearly all children initiated antiretroviral therapy within two weeks of diagnosis. CONCLUSIONS: Multiple missed opportunities for HIV prevention and delays in HIV testing of HIV-exposed children were identified in newly diagnosed children. Findings support critical prevention messaging and retesting of HIV-negative women during pregnancy and breastfeeding, strengthening HIV treatment initiation and follow-up systems and interventions to ensure HIV-positive women receive lifelong antiretroviral therapy throughout the cascade, and broader implementation of community case finding so children not engaged in care receive testing services.

18-24-month HIV-free survival as measurement of the effectiveness of prevention of mother-to-child transmission in the context of lifelong antiretroviral therapy: Results of a community-based survey.

INTRODUCTION: Population-based HIV-free survival at 18-24 months of age among HIV-exposed infants in high prevalence settings in the era of treatment for all is largely unknown. We conducted a community-based survey to determine outcomes of HIV-exposed infants at 18-24 months in Lesotho. METHODS: Between November 2015 and December 2016, we conducted a survey among households with a child born 18-24 months prior to data collection. Catchment areas from 25 health facilities in Butha-Buthe, Maseru, Mohale's Hoek and Thaba-Tseka districts were randomly selected using probability proportional to size sampling. Consecutive households were visited and eligible consenting caregivers and children were enrolled. Rapid HIV antibody testing was performed on mothers of unknown HIV status (never tested or tested HIV-negative >3 months prior) and their children, and to children born to known HIV-positive mothers. Information on demographics, health-seeking behavior, HIV, and mortality were captured for mothers and children, including those who died. The difference in survival between subgroups was determined using the log-rank test. RESULTS: Of the 1,852 mothers/caregivers enrolled, 570 mothers were HIV-positive. The mother-to-child HIV transmission rate was 5.7% [95% CI: 4.0-8.0]. The mortality rate was 2.6% [95% CI: 1.6-4.2] among HIV-exposed children compared to 1.4% (95% CI: 0.9-2.3) among HIV-unexposed children. HIV-free survival was 91.8% [95% CI: 89.2-93.8] among HIV-exposed infants. Disclosure of mother's HIV status (aOR = 4.9, 95% CI: 1.3-18.2) and initiation of cotrimoxazole prophylaxis in the child (aOR = 3.9, 95% CI: 1.2-12.6) were independently associated with increased HIV-free survival while child growth problems (aOR = 0.2, 95% CI: 0.09-0.5) were independently associated with reduced HIV-free survival. CONCLUSION: Even in the context of lifelong antiretroviral therapy among pregnant and breastfeeding women, HIV has a significant effect on survival among HIV-exposed children compared to unexposed children. Lesotho has not reached elimination of HIV transmission from mother to child.

24-Month HIV-free survival among HIV-exposed Infants in Lesotho: the PEAWIL cohort study.

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 identify 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 followed; 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 transmission, but survival of HEI remains lower than their HIV uninfected counterparts.

Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials.

BACKGROUND: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding. METHODS: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938. FINDINGS: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54). INTERPRETATION: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high. FUNDING: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

Association of Antiretroviral Drug Regimen With Viral Suppression in HIV-positive Children on Antiretroviral Therapy in Eswatini.

BACKGROUND: Global pediatric treatment goals are for 90% of known children living with HIV to be on antiretroviral therapy (ART), with 90% having viral suppression. We used enrollment data from a study evaluating a family-centered HIV care program in Eswatini to describe the ART histories and virologic outcomes of enrolled children living with HIV and identify factors associated with viral suppression (<1000 RNA copies/mL) and undetectability (<400 RNA copies/mL). METHODS: Factors associated with viral suppression and undetectability were identified using Pearson χ for categorical variables and Wilcoxon rank sum tests for continuous variables. RESULTS: Three hundred seventy-seven children were enrolled, median age 8.5 years. Median age at HIV diagnosis was 2.1 years; at ART initiation, 2.6 years; and ART duration at enrollment, 4.1 years. Ninety-nine percent were receiving ART; 95.2% were on first-line ART and 4.8% on second-line ART. Most children (43.1%) were receiving nevirapine-based ART (median age 9.2 years), with 31.3% on lopinavir-ritonavir-based (median age 5.4 years) and 25.5%, efavirenz-based ART (median age 10.3 years). Viral suppression (<1000 copies/mL) was observed in 77.9% and undetectability (<400 copies/mL) in 73.5% of children. The only factor significantly associated with viral suppression was ART regimen, with 72.1% of children on nevirapine-based ART versus 86.7% on efavirenz-based ART virally suppressed. CONCLUSIONS: Although 99% of children enrolled in the study were receiving ART, viral suppression was observed in only 77.9%, with lowest rates among children receiving nevirapine-based ART. These findings highlight the critical importance of monitoring treatment regimen for optimizing treatment outcomes for pediatric HIV.

Comparison of 6-week PMTCT outcomes for HIV-exposed and HIV-unexposed infants in the era of lifelong ART: Results from an observational prospective cohort study.

BACKGROUND: Lifelong antiretroviral therapy (ART) reduces mother-to-child HIV transmission (MTCT) and improves maternal health. Data on the outcomes of HIV-exposed infants (HEI) compared to their unexposed counterparts in the era of universal ART is limited. We compared birth and 6-week outcomes among infants born to HIV-positive and HIV-negative women in Lesotho. METHODS: 941 HIV-negative and 653 HIV-positive pregnant women were enrolled in an observational cohort to evaluate the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) program after implementation of universal maternal ART in 14 health facilities. Pregnancy, delivery, birth, and 6-week data were collected through participant interviews and medical record review. DNA PCR testing for HEI was conducted within 2 weeks of birth and at around 6 weeks of age. Data were analysed to estimate the distribution of birth outcomes, mortality, HIV transmission and HIV-free survival at 6 weeks. RESULTS: HIV-positive women were older (mean age of 28.7 vs. 24.4 years) and presented for antenatal care earlier (mean gestational age of 23.0 weeks vs 25.3 weeks) than HIV-negative women. Prematurity was more frequent among HEI, 7.8% vs. 3.6%. There was no difference in rates of congenital anomalies between HEI (1.0%) and HIV-unexposed infants (HUI) (0.6%). Cumulative HIV transmission was 0.9% (N = 4/431) (95% CI:0.25-2.36) at birth and 1.0% (N = 6/583) (95% CI:0.38-2.23) at 6 weeks. Overall mortality, including stillbirths, was 5.2% and 6.0% by 6 weeks for HUI and HEI respectively. Among liveborn infants, 6-week HIV-free survival for HEI was 95.6% (95% CI:93.7-97.1) compared to 96.8% (95% CI:95.4-97.9) survival for HUI. CONCLUSIONS: Implementation of universal maternal ART lowers MTCT at 6 weeks of age with no differences in congenital anomalies or early mortality between HIV exposed Infants and HIV unexposed infants. However, HIV exposed infants continue to have high rates of prematurity despite improved maternal health on ART.

Piloting very early infant diagnosis of HIV in Lesotho: Acceptability and feasibility among mothers, health workers and laboratory personnel.

INTRODUCTION: Mortality associated with in-utero HIV infection rises rapidly within weeks after birth. Very early infant diagnosis of HIV (VEID)-testing within 2 weeks of birth-followed by immediate initiation of antiretroviral therapy has potential to avert mortality associated with in-utero transmission. However, our understanding of acceptability and feasibility of VEID is limited. METHODS: VEID was piloted in an observational prospective cohort of HIV-positive pregnant women and their infants in 13 Lesotho health facilities. Between March-July 2016, semi-structured interviews were conducted with HIV-positive women attending 6-week or 14-week postnatal visits and health workers (HWs) in 8 study facilities in 3 districts as well as with district and central laboratory staff. Interview themes included acceptability of birth and subsequent HIV testing and early treatment, perceived VEID challenges, and HIV birth testing procedures and how well they were performed. RESULTS: Interviews were conducted with 20 women, 18 HWs and 9 district/central laboratory staff. Nearly all mothers perceived knowing their child's HIV status at birth positively. Mothers and HWs did not indicate that birth testing affected subsequent acceptance of infant HIV testing or clinic attendance. HWs and laboratory staff reported weak follow-up systems for mothers with home deliveries, and concern regarding the increased workload associated with additional testing requirements. All groups reported turnaround time delays for EID, and that sometimes results were never received. CONCLUSIONS: Women, HWs, and laboratory staff found VEID acceptable and were supportive of national implementation of birth testing. However, they identified challenges within the EID system that could be exacerbated by adding a test to the diagnostic algorithm, such as delays in receiving test results, suggesting VEID may not be feasible in certain settings. Policymakers will need to consider whether adding birth testing or strengthening the current clinic and laboratory system is the most appropriate course of action.

HIV incidence among pregnant and postpartum women in a high prevalence setting.

In sub-Saharan Africa, most women who test HIV negative at the first antenatal care encounter are rarely tested again during pregnancy and postpartum, yet data suggests that pregnancy is associated with increased risk of HIV acquisition compared to non-pregnant women. We describe HIV incidence during pregnancy and postpartum in Lesotho, a high prevalence setting, and factors associated with HIV seroconversion. We enrolled a cohort of HIV negative women presenting at health facilities for antenatal care and followed them through delivery up to 24 months postpartum. Women were repeatedly tested for HIV according to the Lesotho Ministry of Health routine rapid HIV testing guidelines and responded to risk behavior questionnaire every three months. We estimated HIV incidence and associated 95% confidence intervals. We used mixed effects Cox regression models to identify independent factors associated with seroconversion accounting for repeated assessment. The estimated overall HIV incidence rate was 1.58 (95% CI: 1.05-2.28) per 100 person- years. The estimated HIV incidence rate during pregnancy (2.61 per 100 person-years, 95% CI: 1.12-5.14) was almost double the estimated HIV incidence during postpartum (1.36 per 100 person-years, 95% CI: 0.83-2.10). Women's age (14-24 years compared to 25-45 years), multiple sexual partnerships, urethral discharge and no condoms nor pre-exposure prophylaxis were independently associated with HIV infection. There is an increased need for counseling and support of HIV-uninfected pregnant and breastfeeding women to stay HIV-negative, including provision of pre-exposure prophylaxis during this high-risk period, particularly among adolescent and young women.

Making Implementation Science Work for Children and Adolescents Living With HIV.

The global HIV response is leaving children and adolescents behind. Because of a paucity of studies on treatment and care models for these age groups, there are gaps in our understanding of how best to implement services to improve their health outcomes. Without this evidence, policymakers are left to extrapolate from adult studies, which may not be appropriate, and can lead to inefficiencies in service delivery, hampered uptake, and ineffective mechanisms to support optimal outcomes. Implementation science research seeks to investigate how interventions known to be efficacious in study settings are, or are not, routinely implemented within real-world programmes. Effective implementation science research must be a collaborative effort between government, funding agencies, investigators, and implementers, each playing a key role. Successful implementation science research in children and adolescents requires clearer policies about age of consent for services and research that conform to ethical standards but allow for rational modifications. Implementation research in these age groups also necessitates age-appropriate consultation and engagement of children, adolescents, and their caregivers. Finally, resource, systems, technology, and training must be prioritized to improve the availability and quality of age-/sex-disaggregated data. Implementation science has a clear role to play in facilitating understanding of how the multiple complex barriers to HIV services for children and adolescents prevent effective interventions from reaching more children and adolescents living with HIV, and is well positioned to redress gaps in the HIV response for these age groups. This is truer now more than ever, with urgent and ambitious 2020 global targets on the horizon and insufficient progress in these age groups to date.

Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine.

OBJECTIVES: Use of single dose nevirapine (SD NVP) for prevention of HIV-1 mother-to-child transmission (pMTCT) is associated with selection of K103N-containing HIV variants. Repeat use of SD NVP for pMTCT may influence emergence and persistence of NVP-resistant variants. DESIGN: K103N-containing variants were studied in 48 Ugandan women who received SD NVP in the HIVNET 012 trial, and were re-exposed to SD NVP in one (n = 44) or two (n = 4) subsequent pregnancies during a 5-year follow-up study. METHODS: Samples were analyzed using the LigAmp assay (assay cutoff: 0.5% K103N). RESULTS: Among 44 women who were re-exposed to SD NVP in one subsequent pregnancy, 37.8% had K103N detected within 1 year of SD-NVP re-exposure. Detection of K103N was independently associated with detection of K103N 6-8 weeks after the first SD NVP exposure and with pre-NVP viral load. The portion of women with undetectable K103N by 2 years after SD NVP administration was similar after first versus second use of SD NVP for pMTCT. K103N was undetectable in 93.2% of evaluable women by 3 years of re-exposure. Only two of four women who received SD NVP in two pregnancies during the follow-up study had K103N detected after the last SD NVP exposure. CONCLUSIONS: K103N was detected in some women within 1 year of SD NVP re-exposure, but faded from detection in most women by 3 years after re-exposure. Detection of K103N by 1 year after SD NVP re-exposure was associated with prior selection of K103N-containing variants and with pre-NVP viral load.

HIV type 1 variants with nevirapine resistance mutations are rarely detected in antiretroviral drug-naive African women with subtypes A, C, and D.

K103N is frequently detected in HIV-infected women after single dose (SD) nevirapine (NVP). K103N-containing variants were detected more frequently by the ViroSeq HIV-1 Genotyping System in women with subtype C (69.2%) than subtypes A (19.4%, p < 0.0001) or D (36.1%, p < 0.0001). K103N-containing variants were also detected more frequently and at higher levels in women with subtype C by the LigAmp assay. In this report, we analyzed samples collected prior to or within hours after SD NVP administration from antiretroviral drug-naive African women with subtypes A, C, and D. Only 1/254 samples had an NVP resistance mutation detected with the ViroSeq system, and only 4/236 samples had K103N detected at < 0.5% with the LigAmp assay [2/110 (1.8%) with subtype A, 1/46 (2.2%) with subtype C, and 1/80 (1.3%) with subtype D] (p = 0.92). We did not detect significant differences in the pre-NVP frequency of NVP resistance mutations or the pre-NVP levels of K103N-containing variants in women with subtypes A, C, and D that explain the dramatic subtype-based differences in emergence of HIV-1 variants with these mutations after SD NVP exposure.