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BACKGROUND: Maternal HIV and antiretroviral therapy exposure in-utero may influence infant weight, but the contribution of maternal y body mass index (BMI) to early life overweight and obesity is not clear. OBJECTIVE: To estimate associations between maternal BMI at entry to antenatal care and infant weight through approximately 1 year of age and to evaluate if associations were modified by maternal HIV status, maternal HIV and viral load, breast feeding intensity through 6 months or timing of entry into antenatal care. METHODS: We followed HIV-uninfected and -infected pregnant women initiating efavirenz-based antiretroviral therapy from first antenatal visit through 12 months postpartum. Infant weight was assessed via World Health Organization BMI and weight-for-length (WL) z-scores at 6 weeks, 3, 6, 9, and 12 months. We used multivariable linear mixed effects models to estimate associations between maternal BMI and infant z-scores over time. RESULTS: In 861 HIV-uninfected infants (454 HIV-exposed; 407 HIV-unexposed), nearly 20% of infants were overweight or obese by 12 months of age, regardless of HIV-exposure status. In multivariable analyses, increasing maternal BMI category was positively associated with higher infant BMIZ and WLZ scores between 6 weeks and 12 months of age and did not differ by HIV exposure status. However, HIV-exposed infants had slightly lower BMIZ and WLZ trajectories through 12 months of age, compared to HIV-unexposed infants across all maternal BMI categories. Differences in BMIZ and WLZ scores by HIV exposure were not explained by timing of entry into antenatal or maternal viral load pre-antiretroviral therapy initiation, but z-scores were slightly higher for HIV-exposed infants who were predominantly or exclusively versus partially breast fed. CONCLUSIONS: These findings suggest maternal BMI influences early infant weight gain, regardless of infant HIV-exposure status. Intervention to reduce maternal BMI may help to address growing concerns about obesity among HIV-uninfected children.

Contains fulltext : 235789.pdf (Publisher’s version ) (Open Access) Information on the extent of drug exposure to mothers and infants during pregnancy and lactation normally becomes available years after regulatory approval of a drug. Clinicians face knowledge gaps on drug selection and dosing in pregnancy and infant exposure during breastfeeding. Physiological changes during pregnancy often result in lower drug exposures of antiretrovirals, and in some cases a risk of reduced virologic efficacy. The International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) network and the World Health Organization (WHO)-convened Pediatric Antiretrovirals Working Group collaboratively organized a workshop of key stakeholders in June 2019 to define key standards to generate pharmacology data for antiretrovirals to be used among pregnant and lactating women; review the antiretroviral product pipeline; describe key gaps for use in low-income and middle-income countries; and identify opportunities to undertake optimal studies allowing for rapid implementation in the clinical field. We discussed ethical and regulatory principles, systemic approaches to obtaining data for pregnancy pharmacokinetic/pharmacodynamic (PK/PD) studies, control groups, optimal sampling times during pregnancy, and pharmacokinetic parameters to be considered as primary end points in pregnancy PK/PD studies. For lactation studies, the type of milk to collect, ascertainment of maternal adherence, and optimal PK methods to estimate exposure were discussed. Participants strongly recommended completion of preclinical reproductive toxicology studies prior to phase III, to allow study protocols to include pregnant women or to allow women who become pregnant after enrolment to continue in the trial. The meeting concluded by developing an algorithm for design and interpretation of results and noted that recruitment of pregnant and lactating women into clinical trials is critical.

Objective We examined the longitudinal association between women's exposure to intimate partner violence (IPV) and HIV viral load during pregnancy and postpartum. Design Secondary analysis of an HIV-positive cohort enrolled during pregnancy at a South African antenatal clinic. Methods Viral load was assessed at 10 study visits and analyzed continuously as log10 copies/ml and suppression at less than 50 copies/ml. IPV was measured at three timepoints using behaviorally specific items. We used multivariate logistic regression to examine the association between IPV and viral suppression, and cross-lagged dynamic panel modeling (DPMs) to estimate the longitudinal association between IPV (lagged by 3-6 months) and log10 viral load. Results Of 471 women, 84% were virally suppressed by 6 weeks postpartum and 67% at 12 months postpartum. One-third reported IPV exposure. IPV victimization was not associated with viral suppression at delivery, but was associated with a reduced odds of viral suppression at 12 months postpartum (aOR = 0.48, 95% CI = 0.27-0.85). Findings were robust to sensitivity analyses at different timepoints and clinical cut-points. In DPMs, lagged IPV exposure was associated with higher log10 viral load after controlling for past viral load, duration on ART, age, alcohol use, and gestation at study enrolment. Each standardized increase in IPV intensity was associated with higher log10 viral load (standardized coefficient = 0.12, 95% CI = 0.05-0.23). Conclusion Although viral suppression was widely achieved during pregnancy, suppression rates declined postpartum in this South African cohort. These data suggest IPV is longitudinally associated with elevated viral load postpartum. Interventions for reducing exposure to IPV are important for the health of women and may improve HIV care and treatment.

Mother-child pairs may separate during early life, yet the health impacts thereof are unclear. We explored the patterns and impact of separation among women living with HIV (WLHIV) and their children in South Africa.WLHIV who had initiated antiretroviral therapy (ART) during pregnancy received HIV viral load (VL) testing and completed a timeline questionnaire of mother-child separation since delivery at 3-5 years post-partum. Health care usage was abstracted from routine medical records. We examined associations between separation and (a) maternal health outcomes (engagement in HIV care and HIV viral suppression, [VS]) and (b) child health outcomes (post-breastfeeding HIV testing and immunisation completion), using logistic regression.Of 346 mother-child pairs (median maternal age at antenatal ART initiation, 28 years), 24% were ever separated (median time to first separation 20 months, interquartile range [IQR] 9, 31). Most separated children were living with their grandmothers (65/83, 78%). Mothers who ever separated were younger, and more likely to be employed, and to reside in informal housing than those who never separated. Any separation reduced the odds of VS ≤ 50 copies/mL at four years post-partum (odds ratio 0.57; 95% CI 0.34-0.93); associations were similar for VL ≤ 1000 copies/mL and maternal engagement in care. No association was found between separation and child confirmatory HIV testing or immunisation completion.In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.Les couples mère-enfant peuvent être séparés au début de la vie, mais les effets sur la santé ne sont pas clairs. Nous avons exploré les modèles et l'impact de la séparation chez les femmes vivant avec le VIH (PVVIH) et leurs enfants en Afrique du Sud. MÉTHODES: Les PVVIH qui avaient initié un traitement antirétroviral (ART) pendant la grossesse ont subi un test de charge virale du VIH (CV) et ont rempli un questionnaire chronologique sur la séparation mère-enfant depuis l'accouchement à 3-5 ans post-partum. L'utilisation des soins de santé a été extraite des dossiers médicaux de routine. Nous avons examiné les associations entre la séparation et (a) les résultats pour la santé maternelle (engagement dans les soins du VIH et la suppression virale du VIH [SV]) et (b) les résultats pour la santé de l'enfant (dépistage du VIH après l'allaitement et achèvement de la vaccination), en utilisant la régression logistique. RÉSULTATS: Sur 346 couples mère-enfant (âge maternel médian au début de l’ART prénatal, 28 ans), 24% ont été séparés (délai médian jusqu'à la première séparation 20 mois, intervalle interquartile [IQR] 9 à 31). La plupart des enfants séparés vivaient avec leurs grands-mères (65/83, 78%). Les mères qui ont vécu une telle séparation étaient plus jeunes et plus susceptibles d'avoir un emploi et de vivre dans un logement informel que celles qui ne l’ont jamais vécue. Toute séparation réduisait les chances de SV ≤50 copies/mL à quatre ans après l'accouchement (odds ratio 0,57; IC95%: 0,34-0,93); les associations étaient similaires pour la CV ≤1000 copies/mL et l'engagement de la mère dans les soins. Aucune association n'a été trouvée entre la séparation et le test de confirmation du VIH chez l'enfant ou l'achèvement de la vaccination.Dans ce contexte, la séparation mère-enfant est courante au cours des quatre premières années de la vie et semble associée à des résultats maternels sous-optimaux. Des recherches supplémentaires sont nécessaires pour comprendre les facteurs et les implications de la séparation mère-enfant.

BACKGROUND With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis. METHODS As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa. Infant VL and CD4+ T-cell parameters were measured before ART initiation. Data were collected on maternal characteristics, including VL, CD4+ T-cell counts and ART, and infant characteristics, including sex, birth weight, and mode of delivery. RESULTS Pre-ART, median infant VL was 28,405 copies/mL [interquartile range (IQR): 2515-218,150], CD4+ T-cell count 1914 cells/mm (IQR: 1474-2639) and percentage 40.8% (IQR: 32.2-51.2). Most (80.4%) infants were born to mothers who received ART during pregnancy and 97.9% of infants received daily nevirapine prophylaxis until ART initiation at median of 2 days of age (IQR: 1-7). Infant pre-ART VL was more likely to be ≥1000 copies/mL when their mothers had VL ≥1000 copies/mL [Odds Ratio (OR): 6.88, 95% confidence interval (CI): 2.32-20.41] and was higher in boys than girls (OR: 3.29, 95% CI: 1.07-9.95). Lower maternal CD4+ T-cell count (

Background Children living with human immunodeficiency virus (HIV) (CLHIV) receiving antiretroviral therapy (ART) in resource-limited settings are susceptible to high rates of acquired HIV drug resistance (HIVDR), but few studies include children initiating age-appropriate World Health Organization (WHO)-recommended first-line regimens. We report data from a cohort of ART-naive South African children who initiated first-line ART. Methods ART-eligible CLHIV aged 0–12 years were enrolled from 2012 to 2014 at 5 public South African facilities and were followed for up to 24 months. Enrolled CLHIV received standard-of-care WHO-recommended first-line ART. At the final study visit, a dried blood spot sample was obtained for viral load and genotypic resistance testing. Results Among 72 successfully genotyped CLHIV, 49 (68.1%) received ABC/3TC/LPV/r, and 23 (31.9%) received ABC/3TC/EFV. All but 2 children on ABC/3TC/LPV/r were Conclusions High levels of NNRTI and NRTI DRMs among CLHIV receiving ABC/3TC/LPV/r suggests a lasting impact of failed mother-to-child transmission interventions on DRMs. However, drug susceptibility analysis reveals that CLHIV with detectable viremia on ABC/3TC/LPV/r are more likely to have maintained at least 2 effective agents on their current HIV regimen than those on ABC/3TC/EFV.

South Africa faces dual epidemics of HIV and obesity; however, little research has explored whether HIV status influences associations between pre-pregnancy body mass index (BMI) and adverse birth outcomes.To examine associations between pre-pregnancy body mass index (BMI) and adverse birth outcomes, and if they differ by HIV status.We followed HIV-uninfected and -infected pregnant women initiating antiretroviral therapy (ART) from first antenatal visit through delivery. HIV-infected women initiated ART (tenofovir-emtricitabine/lamivudine-efavirenz) in pregnancy. Estimated pre-pregnancy BMI (kg/mAmong 1116 women (53% HIV-infected), 44% of HIV-uninfected women and 36% of HIV-infected women were classified as obese; 4% of women were underweight. Overall, 12% of infants were delivered preterm (37 weeks), 10% small for gestational age (SGA,10th percentile), and 9% large for gestational age (LGA,90th percentile). Compared to HIV-uninfected women, HIV-infected women on ART had less LGA (5% vs 13%) but more SGA (12% vs 8%), and a similar proportion of preterm (13% vs 11%) infants. Pre-pregnancy BMI was not associated with preterm birth. Among HIV-uninfected women, obesity modestly increased the risk of LGA (RR 1.34, 95% confidence interval [CI] 0.82, 2.19), and underweight modestly elevated the risk of SGA (RR 1.66, 95% CI 0.79, 3.46). These associations were attenuated among HIV-infected women (RR 1.07, 95% CI 0.44, 2.64 for LGA, and RR 1.34, 95% CI 0.49, 3.64 for SGA).In this urban African setting of high HIV prevalence, pre-pregnancy obesity was common and did not vary by HIV status. In HIV-uninfected women, obesity increased the risk of LGA and being underweight the risk of SGA, compared with among HIV-uninfected women.

Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)§ survey data, pooled from eight sub-Saharan African countries¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Key populations, ie, female sex workers, men who have sex with men, transgender people, people who inject drugs, and people in prisons and other closed settings, experience stigma, discrimination, and structural barriers when accessing HIV prevention and care. Public health facilities in Myanmar became increasingly involved in HIV service delivery, leading to an urgent need for healthcare workers to provide client-centred, key population-friendly services. Between July 2017–June 2018, the Myanmar Ministry of Health and Sports and National AIDS Programme collaborated with ICAP at Columbia University and the US Centers for Disease Control and Prevention to implement a quasi-experimental, multicomponent intervention including healthcare worker sensitization training with pre- and post- knowledge assessments, healthcare worker and client satisfaction surveys, and structural changes. We observed modest improvements among healthcare workers (n = 50) in knowledge assessments. Classification of clients into key population groups increased and fewer clients were classified as low risk. Key population clients reported favourable perceptions of the quality and confidentiality of care through self-administered surveys. Our findings suggest public health facilities can deliver HIV services that are valued by key population clients.

BACKGROUND: Prompt initiation of antiretroviral therapy (ART) for HIV-infected infants is strongly recommended but diagnostic confirmation is important as committing children to life-long ART carries serious health and social implications. METHODS: Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load (VL) results. RESULTS: Case 1 had repeat indeterminate NAAT results during the first three weeks of life; repeat testing thereafter was negative with undetectable VL including after daily nevirapine prophylaxis ended. ART was not initiated at this time. Case 2 had a single positive NAAT result at one month of age that prompted initiation of ART. Subsequent results were negative and ART was discontinued. Repeat negative NAAT with VL below the limit of quantification or undetectable continued to be obtained. Shortly after and around weaning, positive NAAT results with high VL (7.1 and 6.03 log(10) copies/ml for Case 1 and 2, respectively) were observed in both children. Both mothers were treated with tenofovir, emtricitabine and efavirenz during breastfeeding. Testing with ultrasensitive assays on early samples conclusively revealed HIV-1 proviral DNA in Case 1. Testing with ultrasensitive assays after the early period but prior to weaning did not detect HIV in either infant. CONCLUSION: We hypothesize that breast milk from the mothers of these two rare cases had HIV-specific or non-specific factors that led to the undetectable results in already infected infants until breastfeeding ended. Our results raise the importance of repeat testing of HIV-exposed breastfed infants after complete cessation of all breastfeeding.

Summary Antiretroviral agents with long-acting properties have potential to improve treatment outcomes substantially for people living with HIV. In November 2017, the Long acting/Extended Release Antiretroviral Resource Program (LEAP) convened a workshop with the aim of shaping the research agenda and promoting early development of long-acting or extended release products for key populations: pregnant and lactating women, children aged up to 10 years, and adolescents aged 10–19 years. Goals included strategies and principles to ensure that the needs of children, adolescents, and pregnant and lactating women are considered when developing long-acting formulations. Research should focus not only on how best to transition long-acting products to these populations, but also on early engagement across sectors and among stakeholders. A parallel rather than sequential approach is needed when establishing adult, adolescent, and paediatric clinical trials and seeking regulatory approval. Pregnant and lactating women should be included in adult clinical trials. Adolescent-friendly trial design is needed to improve recruitment and retention of young people.

BACKGROUND Poor growth and metabolic disturbances remain concerns for children living with HIV (CLHIV). We describe the impact of viral load (VL) on growth and lipid outcomes in South African CLHIV

Transitions between services for continued antiretroviral treatment (ART) during and after pregnancy are a commonly overlooked aspect of the HIV care cascade, but ineffective transitions can lead to poor health outcomes for women and their children. In this qualitative study, we conducted interviews with 15 key stakeholders from Ministries of Health along with PEPFAR-supported and other in-country non-governmental organizations actively engaged in national programming for adult HIV care and prevention of mother-to-child-transmission of HIV (PMTCT) services in Côte d’Ivoire, Lesotho and Malawi. We aimed to understand perspectives regarding transitions into and out of PMTCT services for continued ART. Thematic analysis revealed that, although transitions of care are necessary and a potential point of loss from ART care in all three countries, there is a lack of clear guidance on transition approach and no formal way of monitoring transition between services. Several opportunities were identified to monitor and strengthen transitions of care for continued ART along the PMTCT cascade.

BACKGROUND There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub-Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG). METHODS We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana, excluding those with pre-existing diabetes. We screened for GDM using a 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks' gestation or at the earliest prenatal visit for those presenting after 28 weeks. Logistic regression models were fitted to assess the association between maternal HIV infection and GDM. Subgroup analyses were performed among WLHIV to assess the association between maternal antiretroviral therapy (ART) in pregnancy [DTG vs. efavirenz (EFV) with tenofovir/emtricitabine] and GDM. RESULTS Of 486 pregnant women, 66.5% were WLHIV, and they were older than women without HIV (median age 30 vs. 25 years, P

Background Uptake and retention in antenatal care (ANC) is critical for preventing adverse pregnancy outcomes for both mothers and infants. Methods We implemented a rapid quality improvement project to improve ANC retention at seven health facilities in Eswatini (October-December 2017). All pregnant women attending ANC visits were eligible to participate in anonymous tablet-based audio assisted computer self-interview (ACASI) surveys. The 24-question survey asked about women’s interactions with health facility staff (HFS) (nurses, mentor mothers, receptionists and lab workers) with a three-level symbolic response options (agree/happy, neutral, disagree/sad). Women were asked to self-report HIV status. Survey results were shared with HFS at monthly quality improvement sessions. Chi-square tests were used to assess differences in responses between months one and three, and between HIV-positive and negative women. Routine medical record data were used to compare retention among pregnant women newly enrolled in ANC two periods, January-February 2017 (‘pre-period’) and January-February 2018 (‘post-period’) at two of the participating health facilities. Proportions of women retained at 3 and 6 months were compared using Cochran-Mantel-Haenszel and Wilcoxon tests. Results A total of 1,483 surveys were completed by pregnant women attending ANC, of whom 508 (34.3%) self-reported to be HIV-positive. The only significant change in responses from month one to three was whether nurses listened with agreement increasing from 88.3% to 94.8% (p Conclusion The type of rapid quality improvement intervention we implemented may be useful in improving patient-provider relationships although whether it can improve retention remains unclear.

Item does not contain fulltext BACKGROUND: Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV), and their infants. SETTING: The World Health Organization convened a Paediatric Antiretroviral Drug Optimization group meeting, December 10-12, 2018, in Geneva, Switzerland. METHODS: The group, comprised of clinicians, scientists, HIV program managers, regulators, and community representatives, were tasked to consider how ARVs are studied in PWLHIV, define alternative approaches to studying ARVs in PWLHIV, identify ways to shorten the timeline to determine safe use of new agents during pregnancy, and define strategies to collaborate with regulators and industry to change longstanding practices. RESULTS: Most new ARVs are not studied in pregnant populations until after drug licensure, primarily opportunistically among women who become pregnant while taking the ARV of interest. Acceleration of the timeline will require earlier completion of preclinical studies and a new paradigm, namely-under certain conditions-allow women who become pregnant while participating in phase III ARV studies the option of remaining on study and enroll pregnant women into phase III trials of new agents to obtain preliminary safety and dosing and efficacy data. CONCLUSION: A revision of the current approach to the study of antiretrovirals in pregnant women is urgently needed to improve timely access and safe use of new agents during pregnancy.

BackgroundAdolescents living with HIV (ALHIV) 15–19 years of age are a growing proportion of all people living with HIV globally and the population includes adolescents with vertically acquired HIV (AVH) and behaviorally acquired HIV (ABH).MethodsWe conducted a survey to measure sociodemographic characteristics, educational status, health history, and antiretroviral therapy (ART) adherence among a convenience sample of ALHIV at three government health facilities in 2019 in Nampula, Mozambique. ALHIV 15–19 years on ART, including females attending antenatal care, were eligible. Routine HIV care data were extracted from medical charts. Classification of ALHIV by mode of transmission was based on medical charts and survey data. ALHIV who initiated ART ResultsAmong 208 ALHIV, 143 (69%) were female and median age was 18 years [interquartile range (IQR) 16–19]. Just over half of ALHIV (53%) were in or had completed secondary or higher levels of education; the most common reason for not being in school reported by 36% of females was pregnancy or having a child. Of all ALHIV, 122 (59%) had VL data, 62% of whom were DiscussionData from our study underscore the high level of deprivation among ALHIV enrolled in HIV care in Mozambique, as well as important disparities by sex and mode of transmission. These data can inform the development of effective interventions for this complex and important population.

Background: Pregnant and breastfeeding adolescents and young women living with HIV (AYWLH) have lower retention in prevention of mother-to-child transmission (PMTCT) services compared to older women. Methods: We evaluated a differentiated service model for pregnant and breast feeding AYWLH at seven health facilities in western Kenya. All pregnant AYWLH

IntroductionAdolescents living with HIV have poor antiretroviral therapy (ART) adherence and viral suppression outcomes. Viral load (VL) monitoring could reinforce adherence but standard VL testing requires strong laboratory capacity often only available in large central laboratories. Thus, coordinated transport of samples and results between the clinic and laboratory is required, presenting opportunities for delayed or misplaced results. Newly available point-of-care (POC) VL testing systems return test results the same day and could simplify VL monitoring so that adolescents receive test results faster which could strengthen adherence counselling and improve ART adherence and viral suppression.Methods and analysisThis non-blinded randomised clinical trial is designed to evaluate the implementation and effectiveness of POC VL testing compared with standard laboratory-based VL testing among adolescents and youth living with HIV in Haiti. A total of 150 participants ages 10–24 who have been on ART for >6 months are randomised 1:1 to intervention or standard arms. Intervention arm participants receive a POC VL test (Cepheid Xpert HIV-1 Viral Load system) with same-day result and immediate ART adherence counselling. Standard care participants receive a laboratory-based VL test (Abbott m2000sp/m2000rt) with the result available 1 month later, at which time they receive ART adherence counselling. VL testing is repeated 6 months later for both arms. The primary objective is to describe the implementation of POC VL testing compared with standard laboratory-based VL testing. The secondary objective is to evaluate the effect of POC VL testing on VL suppression at 6 months and participant comprehension of the correlation between VL and ART adherence.Ethics and disseminationThis study is approved by GHESKIO, Weill Cornell Medicine and Columbia University ethics committees. This trial will provide critical data to understand if and how POC VL testing may impact adolescent ART adherence and viral suppression. If effective, POC VL testing could routinely supplement standard laboratory-based VL testing among high-risk populations living with HIV.Trial registration numberNCT03288246.

OBJECTIVE: To examine associations between high blood pressure (BP) when entering antenatal care (ANC) and birth outcomes in a cohort of pregnant HIV- and women living with HIV (WLHIV) initiating antiretroviral treatment (ART). STUDY DESIGN: Prospective cohort study. MAIN OUTCOME MEASURES: Cesarean delivery, preterm birth (10(th) percentile for GA). RESULTS: Of 1116 women (median GA 20 weeks; WLHIV 53%), 48% (53% WLHIV; 43% HIV-) entered ANC with high BP, defined as elevated (120–129 or 130–139 or 80–89) or stage 2 hypertension (≥140 / or ≥90). WLHIV were more likely to have high BP (RR 1.32; 95%CI 1.12-1.57), controlling for pre-pregnancy body mass index and additional confounders. In multivariable analysis, there was no evidence that high BP increased the risk of cesarean delivery (RR 1.10, 95% CI 0.92-1.30), preterm birth (RR 1.15, 95% CI 0.81-1.62), LBW (RR 1.16, 95% CI 0.84-1.60) or SGA (RR 1.02, 0.72-1.44), overall or when stratified by HIV-status. High BP was associated with an increased risk of LGA (RR 1.43; 95% CI 1.00-2.03). CONCLUSION: In this setting, half of women had high BP at entry into ANC, with WLHIV at increased risk of high BP. There was no strong evidence that high BP increased the risk of adverse birth outcomes overall, or by HIV-status, with the exception of LGA. WLHIV may be at high risk of high BP during pregnancy and should be monitored closely.

Universal eligibility for lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') has been widely adopted, but concerns remain. We tested the hypothesis that the change from CD4+-guided ART eligibility ('Option A'), to Option B+, would improve maternal ART uptake and retention.A stepped-wedge evaluation at 12 health facilities in eSwatini.Primary outcome was maternal retention: proportion of women attending clinic within 56 days of delivery (antenatal retention) and clinic attendance within 84 days of 6-months postpartum (postnatal retention). Generalized estimating equations examined impact of Option B+ vs. Option A.Between 19 August 2013 and 29 August 2014, 2347 HIV-positive women, 55% (n = 1296) Option A, 45%, (n = 1051) Option B+ were included. ART initiation was observed in 36% (n = 469) of Option A women vs. 94% (n = 983) under Option B+ (P 0.001). Overall 39% (n = 912) were retained from first ANC visit through 6-months postpartum. Retention was higher under Option B+ (53%, n = 559) vs. Option A (24%, n = 353) with variation by site and study month. Adjusting for age, gestational age, previous HIV diagnosis, and CD4+, Option B+ women were significantly more likely to be retained antenatally (aRR 1.32; 95% CI 1.18-1.49; P 0.001) and postnatally (aRR 2.11; 95% CI 1.79-2.49) compared with Option A. Restricted to women initiating ART, retention was lower under Option B+ (57%, n = 558) vs. Option A (66%, n = 309; aRR, 0.82; 95% CI 0.70-0.95; P 0.0001).Compared with CD4+-guided ART eligibility, universal ART resulted in substantial increases in pregnant women initiating ART and retained in care through 6 months postpartum.

Elevated HIV viral load (VL) in pregnancy has been linked to increased risk of mortality, immunologic abnormalities, infectious morbidity and restricted growth among HIV-exposed uninfected (HEU) children, but little is known about effects on child development.HIV-infected women initiating lifelong antiretroviral therapy (ART; tenofovir + emtricitabine + efavirenz) antenatally were followed from first antenatal visit through delivery and with their breastfed infants postpartum. Cognitive, motor and expressive language development (Bayley Scales of Infant and Toddler Development-Third Edition; delay defined as score85) were assessed on a subset of HEU infants. HIV VL was measured at ART initiation, in third trimester and around delivery. Cumulative viremia in pregnancy was expressed as log10 VL copies × year/mL [viremia copy-years (VCY)]. Relationships between VCY and development were examined after adjusting for socioeconomic, behavioral and psychosocial confounders.Women (median pre-ART log10 VL 4.1, CD4 349 cells/mm) commonly reported adverse social circumstances (44% informal housing, 63% unemployed, 29% risky drinking). Among 214 infants (median age, 13 months; 53% male; 13% born37 weeks' gestation), viremia predicted lower motor and expressive language, but not cognitive, scores in crude and adjusted analysis [per log10 VCY increase, αβ (95% confidence interval [CI]): motor, -2.94 (-5.77 to -0.11); language, -3.71 (-6.73 to -0.69) and cognitive -2.19 (-5.02 to 0.65)]. Increasing VCY also predicted higher relative odds of motor delay [adjusted odds ratio (aOR): 3.32; 95% CI: 1.36-8.14) and expressive language delay (aOR: 2.79; 95% CI: 1.57-4.94), but not cognitive delay (aOR: 1.68; 95% CI: 0.84-3.34).Cumulative maternal HIV viremia in pregnancy may have adverse implications for HEU child development.

Objective Identify factors associated with trajectories of psychiatric disorder among 340 adolescents and young adults (AYA) living with perinatal HIV infection (PHIV) and perinatal HIV-exposure but not infection (PHEU). Design Longitudinal cohort study of AYA in New York City, 9-16 years at enrollment. Methods We used multivariate longitudinal latent class analysis to identify trajectories of psychiatric disorder, and logistic regression to examine predictors of trajectories (e.g. PHIV status) and associations between trajectories and viremia in young adulthood (AYA with PHIV only). Results Among all AYA, we identified three psychiatric trajectories: relatively 'low disorder' (63%), 'consistent anxiety' (26%), and 'escalating comorbidity' (11%). Compared with AYA with 'low disorder', AYA with 'escalating comorbidity' were significantly older, reported more neighborhood stress, and lived with a caregiver with alcohol use disorder, whereas AYA with 'consistent anxiety' were more likely female individuals. Although we found no statistically significant HIV status differences, among AYA with PHIV, nearly half (48%) were viremic in young adulthood, with higher odds of viremia among AYA with 'escalating comorbidity' (OR: 3.88, 95% CI: 0.93-16.26) and 'consistent anxiety' (OR: 2.41, 95% CI: 1.011-5.75) compared with 'low disorder'. Conclusion Despite significant adversity, AYA with PHIV and PHEU had relatively low prevalence of psychiatric disorder over time, although one-third had consistent or escalating psychiatric disorders. Among AYA with PHIV, psychiatric trajectories were associated with viremia in young adulthood. Given the growing population of AYA living with PHIV and PHEU worldwide, addressing the substantial and evolving mental health needs of both groups as they reach young adulthood is critical.

BACKGROUND: Perinatal HIV transmission has dramatically decreased with combination antiretroviral (ARV) regimens, but complications among children who are HIV-exposed but uninfected (HEU), such as microcephaly, warrant ongoing surveillance. The goal of our study was to evaluate whether individual in utero ARV exposures were associated with increased risk of microcephaly based on long-term follow up of HEU infants and children. METHODS: We evaluated HEU children enrolled in the Surveillance Monitoring for ART Toxicities (SMARTT) study, a prospective cohort study conducted by the PHACS network. Microcephaly was defined using 2000 CDC Growth z-scores for head circumference (HC) measurements obtained at 6–36 months of age (z-score

Across sub-Saharan Africa, prevention of mother-to-child transmission services are encountering increasing numbers of women already established on antiretroviral therapy (ART) when entering antenatal care. However, there are few data examining ART adherence and HIV viral load in this group. We used multivariable logistic regression models to examine self-reported suboptimal adherence (defined as missed ART doses on ≥2 days during the preceding 30 days), elevated viral load (≥1000 copies/mL), and factors associated with each among women entering antenatal care on ART. Participants were recruited from one primary care clinic in Gugulethu, Cape Town, as part of a larger study of HIV-positive pregnant and postpartum women. Among 482 pregnant women established on ART and enrolled between May 2013 and June 2014 (median age: 31 years; median duration of ART use: 3 years), 15% reported suboptimal adherence and 12% had elevated viral load. After adjustment for age, suboptimal adherence was significantly more common among women who were not married/cohabiting and women who reported a higher level of concern about taking ART; a higher level of adherence self-efficacy was associated with a reduced odds of suboptimal adherence. In a multivariable model, elevated viral load was significantly associated with previous discontinuation of ART, a higher level of concern about taking ART, and report of an unintended pregnancy. Suboptimal adherence and elevated viral load are common among women entering antenatal care already on ART. Our findings highlight specific beliefs and concerns about ART use during pregnancy that should be addressed in counselling messaging, and suggest that family planning should be more effectively integrated into HIV care. Including adherence and viral load monitoring as part of pregnancy planning for women on ART may be important to achieve safer conception and promote healthy pregnancies.

Despite widespread concerns about HIV incidence in pregnant and postpartum women, there are few data from Africa on HIV acquisition in breastfeeding and subsequent mother-to-child transmission. We measured HIV incidence in a prospective cohort of 413 peripartum and breastfeeding women who tested HIV-negative during pregnancy. In 377 woman-years accrued postpartum (median duration of follow-up, 1 year), there were seven women infected after delivery (postpartum incidence, 1.86/100 person-years; 95% confidence interval 0.88-3.89) with transmission to 2/7 (28%) infants.

Objectives Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen. Methods At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally suppressed human immunodeficiency virus (HIV)-infected children ≥36 months of age without lipodystrophy were randomly assigned to continue taking stavudine as part of their ART regimen (n = 106) or to have abacavir substituted for stavudine (n = 107). The children were followed for 56 weeks after randomization in the context of a larger trial of treatment options for ART-experienced children. Results The mean age of the children was 4.3 years, and the mean duration of ART before random assignment was 3.5 years. No differences in virological outcomes, CD4 response, growth, or dyslipidemia were noted between the stavudine and abacavir groups. By 56 weeks, children in the abacavir group had less clinically detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the children in the stavudine group. Conclusion Substituting abacavir for stavudine did not compromise virological response to treatment and was associated with significantly less lipodystrophy. These results support recommendations that favor abacavir in this population.

On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth. The workshop addressed research and regulatory needs involved in the optimization of POC EID testing and challenges associated with implementation of EID, focusing on testing at birth. Scientific gaps and areas of intervention to accelerate and scale-up EID initiatives and birth testing were identified. These include discussion of the evidence supporting an early mortality peak among HIV-infected infant and justifying a role for birth HIV testing, including POC testing; evaluation of the current POC EID technology pipeline and test performance characteristics required for effective programmatic uptake; mathematical modeling of different testing scenarios and solutions with inclusion of birth testing; the adoption of setting-specific EID testing algorithms to achieve efficient linkage to care including early antiretroviral therapy initiation; the development of appropriate quality assurance programs to ensure accuracy of test results and enable sustainability of the testing program. Addressing these gaps and answering these challenges will be important in helping improve outcomes for HIV-infected infants and accelerate achieving the Joint United Nations Program for HIV and AIDS 90-90-90 targets in children.

Background Studies of antiretroviral therapy (ART) use during pregnancy in HIV-infected women have suggested that ART exposure may be associated with adverse birth outcomes. However, there are few data from sub-Saharan Africa where HIV is most common, and few studies involving the World Health Organization's (WHO's) recommended first-line regimens. Methods We enrolled consecutive HIV-infected pregnant women and a comparator cohort of uninfected women at a primary-level antenatal care facility in Cape Town, South Africa. Gestational assessment combined clinical history, examination and ultrasonography; outcomes included preterm (PTD), low birthweight (LBW) and small for gestational age (SGA) deliveries. In analysis we compared birth outcomes between HIV-infected and -uninfected women, and HIV-infected women who initiated ART before vs during pregnancy. Results In 1554 women (mean age 29 years) with live singleton births at time of analysis, 82% were HIV-infected, 92% of whom received a first-line regimen of tenofovir, emtricitabine and efavirenz. Overall, higher levels of PTD [22% vs 13%; odds ratio (OR) 1.94, 95% confidence interval (CI): 1.34, 2.82] and LBW (14% vs 9%; OR 1.62, 95% CI: 1.05, 2.29) were observed in HIV-infected vs uninfected women, although SGA deliveries were similar (9% vs 11%; OR 1.06, 95% CI: 0.71, 1.61). Adjusting for demographic characteristics and HIV disease measures, HIV-infected (vs HIV-uninfected) women had persistently increased odds of PTD [adjusted odds ratio (AOR) 2.03; CI 1.33, 3.10]; associations with LBW were attenuated (AOR 1.47; CI 0.90, 2.40). Among all HIV-infected women, there appeared to be no association between the timing of ART initiation (before or during pregnancy) and adverse birth outcomes. Conclusions These findings suggest that current WHO-recommended ART regimens appear relatively safe in pregnancy, although more data are required to understand the aetiology of preterm delivery in HIV-infected women using ART.

Five million children have died of AIDS-related causes since the beginning of the epidemic. In 2011, the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan) created the political environment to catalyze both the resources and commitment to end pediatric AIDS. Implementation and scale-up have encountered substantial hurdles, however, which have resulted in slow progress. Reasons include a lack of emphasis on testing outside of prevention of mother-to-child transmission services, an overall lack of integration and coordination with other services, a lack of training among providers, low confidence in caring for children living with HIV, and a lack of appropriate formulations for pediatric antiretrovirals. During the Global Plan period, we have learned that simplification is essential to successful decentralization, integration, and task shifting of services; that innovations require careful planning; and that the family is an important unit for delivering HIV care and treatment services. The post-Global Plan phase presents a number of noteworthy challenges that all stakeholders, national programs, and communities must tackle to guarantee universal treatment for children living with HIV. Accelerated action is essential in ensuring that HIV diagnosis and linkage to treatment happen as quickly and effectively as possible. As fewer infants are infected because of effective prevention of mother-to-child transmission interventions and the population of children living with HIV will age into adolescence adapting service delivery models to the epidemic context, and engaging the community will be critical to finding new efficiencies and allowing us to realize a true HIV-free generation-and to end AIDS by 2030.

Background Scale-up and expansion of antiretroviral therapy (ART) for people living with HIV (PLHIV) have been a global priority for more than 15 years. Methods We describe PLHIV at enrollment in care and ART initiation in Ethiopia, Kenya, Mozambique and Tanzania from 2005–2014 and report on enrollment location, CD4 count and loss to follow-up (LTF), death, and combined attrition (LTF and death) pre- and post-ART initiation over time. Pre-ART outcomes were estimated using competing risk and post-ART using Kaplan-Meier estimators; LTF defined as no visit within six months pre-ART and 12 months after ART start. Results From 2005–2014, 884,328 PLHIV enrolled in care at 350 health facilities, median age was 32.0 years (interquartile range [IQR] 26.0–42.0), and majority were female (66.5%). The proportion of PLHIV enrolled at primary and rural facilities increased from 12.9% and 15.3% in 2005–2006 to 43.5% and 41.7% in 2013–2014 (p

In South Africa, up to 40% of pregnant women are living with human immunodeficiency virus (HIV), and 30–45% are obese. However, little is known about the dual burden of HIV and obesity in the postpartum period. In a cohort of HIV‐uninfected and HIV‐infected pregnant women initiating antiretroviral therapy in Cape Town, South Africa, we examined maternal anthropometry (weight and body mass index [BMI]) from 6 weeks through 12 months postpartum. Using multinomial logistic regression, we estimated associations between baseline sociodemographic, clinical, behavioural, and HIV factors and being overweight–obese I (BMI 25 to 35), compared with being underweight or normal weight (BMI

Summary Background Without breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected (HEU) infants have greater infectious morbidity than HIV-unexposed (HU) infants. We hypothesised that with the introduction of universal maternal ART, breastfed HEU and HU infants would have similar morbidity. Methods We prospectively studied a cohort of HIV-infected pregnant women initiating ART, and a parallel group of HIV-uninfected pregnant women, starting from their first antenatal care visit at the Gugulethu Midwife Obstetrics Unit in Cape Town, South Africa. All pregnant women attending their first antenatal care visit were eligible for enrolment if aged 18 years or older and planning to deliver in Cape Town, without gestational age restrictions. HIV-infected women were participants of the Maternal Child Health ART (MCH-ART) study, and HIV-uninfected women were participants of the HIV-Unexposed Uninfected (HU2) study. All enrolled women were followed up during pregnancy and through delivery. At the early neonatal visit (scheduled for the first week after birth), mother–infant pairs who practiced any breastfeeding in the first 7 days of life were eligible for further postnatal follow-up for at least 12 months post partum. HIV infection was excluded among HEU infants at ages 6 weeks and 12 months by PCR. We evaluated the effect of HIV exposure on two primary outcomes: hospitalisation (all-cause and infection-related admission to hospital) and longitudinal prevalence of child infectious illness (diarrhoea and presumed lower respiratory tract infection [LRTI]). Hospitalisation data were abstracted from routine health records. Crude and adjusted incidence rate ratios (aIRRs; with adjustment for maternal HIV disease severity, timing of ART initiation, breastfeeding, timely vaccination, and birth outcomes [gestational size and age]) for infection-related hospitalisations were calculated from Poisson regression models (with variance corrected for clustering). Prevalence of infant infectious illness was based on maternal self-report for the preceding 2 weeks of each visit, with questions based on Demographic and Health Survey (DHS) questionnaires. Infants who acquired HIV infection during follow-up were excluded from this analysis. MCH-ART is registered on ClinicalTrials.gov , NCT01933477 . Findings Pregnant women were recruited between March 20, 2013, and Aug 19, 2015. Mother–infant pairs (HEU, n=459; HU, n=410) were followed up for a median of 12 months until March 24, 2017. Compared with HU infants, HEU infants had more infection-related hospitalisations between the age of 8 days and 3 months (HEU, 34·2 admissions per 100 child-years [24·4–47·9] vs 9·8 per 100 child-years [95% CI 5·1–18·8]; IRR 3·50 [95% CI 1·68–7·30]), but rates were similar at other ages. In infants aged 8 days to 3 months, infection-related hospitalisations for HEU infants with healthier mothers (n=84; ART initiation at 350 cells per μL, HIV viral load Interpretation Despite ART in pregnancy, breastfed HEU infants versus breastfed HU infants had transiently increased infectious morbidity risks in early infancy. However, differences were driven by factors potentially amenable to intervention, including delayed diagnosis and ART initiation in HIV-positive mothers, and suboptimal breastfeeding and vaccination of their infants. Funding US National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, Fogarty Foundation and the Office of AIDS Research.

To evaluate the effectiveness of the prevention of mother-to-child transmission (PMTCT) Option B+ programme in two provinces with high human immunodeficiency virus (HIV) burden in Mozambique over the first four years of programme implementation.We assessed the PMTCT cascade in antenatal care (ANC) from July 2013 to December 2017 using facility-level data and performed a retrospective cohort analysis with patient-level data. We compared the 12-month antiretroviral therapy (ART) retention rates between women with HIV infection who initiated ART under Option B+ ('B+ pregnant') and those who initiated ART for their own health ('own health').A total of 916 280 pregnant women enrolled in ANC. The proportion of women with a documented HIV status increased from 93% in 2013 to 96% in 2017. The proportion of those tested HIV-positive decreased from 8% to 6% while that of those HIV-positive on ART increased from 42% to 95%. Of the 44 377 HIV-positive women included in the analysis, 35% were lost to care. 'B+ pregnant' women initiating ART in 2015 were less likely to have no follow-up (NFU) compared with 'own health' women starting ART during the same period (adjusted odds ratio: 0.77, 95% confidence interval [CI]: 0.64-0.94, P = 0.01). There was no statistical difference between the two groups during the other years in which ART was initiated. Of those returning for care after their first visit (N = 39 801), the 'B+ pregnant' women showed a higher risk of non-retention than the other group (adjusted hazard ratio: 1.14, 95% CI: 1.03-1.25) when ART was initiated in 2013. The risk decreased during the subsequent years, with no difference observed between the groups.PMTCT Option B+ programme scale-up has yielded positive results, including the maintenance of high HIV testing and ART initiation rates in ANC. Challenges still remain, however, in improving immediate engagement in care and long-term retention. Seeking alternative service delivery models to support existing health systems and prevent defaulters is required to achieve the UNAIDS 95-95-95 targets for PMTCT in Mozambique.Evaluer l'efficacité du programme de la prévention de la transmission mère-enfant (PTME) Option B+ dans deux provinces avec une charge élevée du virus de l' immunodéficience humaine (VIH) au Mozambique, au cours des quatre premières années de la mise en œuvre du programme. MÉTHODES: Nous avons évalué la cascade PTME dans les soins des cliniques prénatales (SCP) de juillet 2013 à décembre 2017 à l'aide de données à l’échelle de l'établissement et avons effectué une analyse de cohorte rétrospective avec des données à l’échelle du patient. Nous avons comparé les taux de rétention à 12 mois de la thérapie antirétrovirale (ART) entre les femmes infectées par le VIH qui ont commencé l’ART dans le cadre de l'option B+ (''enceintes B+'') et celles qui ont commencé l’ART pour leur propre santé (''propre santé''). RÉSULTATS: Au total, 916.280 femmes enceintes ont été inscrites dans les SCP. La proportion de femmes avec un statut VIH documenté est passée de 93% en 2013 à 96% en 2017. La proportion de celles testées positives pour le VIH est passée de 8% à 6% tandis que celle des femmes positives au VIH sous ART est passée de 42% à 95%. Sur les 44.377 femmes séropositives incluses dans l'analyse, 35% ont été perdues au cours des soins. Les femmes ''enceintes B+'' qui ont commencé l’ART en 2015 étaient moins susceptibles de ne pas avoir de suivi (NFU) que les femmes ''propre santé'' ayant commencé l’ART au cours de la même période (rapport de cotes ajusté: 0,77 ; intervalle de confiance à 95% [IC]: 0,64-0,94 ; P = 0,01). Il n'y avait aucune différence statistique entre les deux groupes durant les autres années au cours desquelles l’ART a été initiée. Parmi celles retournant pour des soins après leur première visite (N = 39.801), les femmes ''enceintes B+'' présentaient un risque plus élevé de non-rétention que l'autre groupe (rapport de risque ajusté: 1,14 ; IC95%: 1,03-1,25) lorsque l’ART a été initiée en 2013. Le risque diminuait au cours des années suivantes, sans différence observée entre les groupes.Le déploiement du programme PTME Option B+ a donné des résultats positifs, notamment le maintien de taux élevés de dépistage du VIH et d'initiation de l’ART dans les SCP. Il reste cependant des défis à relever pour améliorer l'engagement immédiat dans les soins et la rétention à long terme. La recherche de modèles de prestation de services alternatifs pour soutenir les systèmes de santé existants et prévenir les défaillances est nécessaire pour atteindre les objectifs de l'ONUSIDA 95-95-95 pour la PTME au Mozambique.

Background The NEVEREST-3 (South Africa) and MONOD-ANRS-12206 (Côte d’Ivoire, Burkina Faso) randomized trials found that switching to efavirenz (EFV) in human immunodeficiency virus–infected children >3 years old who were virologically suppressed by ritonavir-boosted lopinavir (LPV/r) was noninferior to continuing o LPV/r. We evaluated the cost-effectiveness of this strategy using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model. Methods We examined 3 strategies in South African children aged ≥3 years who were virologically suppressed by LPV/r: (1) continued LPV/r, even in case of virologic failure, without second-line regimens; continued on LPV/r with second-line option after observed virologic failure; and preemptive switch to EFV-based antiretroviral therapy (ART), with return to LPV/r after observed virologic failure. We derived data on 24-week suppression (, Using the Cost-Effectiveness of Preventing AIDS Complications–Pediatric model to project clinical outcomes, costs, and cost-effectiveness, we show that preemptively switching to efavirenz in virologically suppressed children >3 years old receiving ritonavir-boosted lopinavir (LPV/r) is cost saving compared with continued LPV/r.

Background HIV-status disclosure is widely encouraged by counseling services, in part because it is thought to improve antiretroviral therapy (ART) adherence and thus HIV viral suppression. However, few longitudinal studies have examined the impact of disclosure on HIV viral load (VL) during pregnancy and postpartum. Methods We explored these associations among 1187 women living with HIV, enrolled between March 2013 and June 2014 in Cape Town, South Africa. Results Among women who tested HIV-positive before pregnancy, we observed no association between disclosure and VL at entry into antenatal care among those already on ART, nor at delivery and 12 months postpartum among those initiating ART. Among women who tested HIV-positive during pregnancy and initiated ART subsequently, disclosure to a male partner was associated with a reduced risk of VL ≥50 copies/mL at delivery (adjusted risk ratio: 0.56; 95% confidence interval: 0.31 to 1.01). After stratification by relationship status, this association was only observed among women who were married and/or cohabiting. In addition, disclosure to ≥1 family/community member was associated with a reduced risk of VL ≥50 copies/mL at 12 months postpartum (adjusted risk ratio: 0.69; 95% confidence interval: 0.48 to 0.97) among newly-diagnosed women. Conclusions These findings suggest that the impact of disclosure on VL is modified by 3 factors: (1) timing of HIV diagnosis (before vs. during the pregnancy); (2) relationship to the person(s) to whom women disclose; and (3) in the case of disclosure to a male partner, relationship status. Counseling about disclosure may be most effective if tailored to individual women's circumstances.

Background Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data sources Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target population 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time horizon 5 years. Perspective Societal. Intervention EFV, DTG, and WHO approach. Outcome measures Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of base-case analysis Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of sensitivity analysis Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary funding source National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

International audience; Breastfeeding is a crucial child survival intervention. However, the potential for transmission of viral infections from mother to child presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. In this Review, we compare the transmission dynamics, risk factors, and outcomes of infection with three chronic viruses transmitted through breastmilk: cytomegalovirus, human T-cell lymphotropic virus type 1, and HIV. We provide an overview of intervention approaches and discuss scientific, policy, and programming gaps in the understanding of these major global infections.

Objective To examine unannounced telephone pill counts as a measure of adherence to antiretroviral therapy among adolescents and young adults living with perinatal HIV infection. Methods Participants were recruited from an ongoing longitudinal study to complete four monthly, unannounced telephone pill counts. Detailed notes concerning participants' medication habits surrounding adherence were recorded. Results Two-thirds of 102 eligible participants aged 18-27 years participated; 57% were female, 69% were Black. Blacks and participants with viral loads >40 and >1,000 copies/ml were less likely to participate. Average adherence across calls was 77%. Those who completed all calls averaged significantly higher adherence scores than those who did not. Calls revealed adherence barriers at individual (e.g., medication disorganization), social (e.g., limited support), and system (e.g., pharmacy problems) levels. Conclusions Despite challenges, this procedure can be implemented with this population and can help identify adherence barriers important for interventions that address medication-taking behaviors.

HIV-infected pregnant women in sub-Saharan Africa are at risk for depression and alcohol abuse. Young women may be more vulnerable, but little is known about the psychosocial functioning of this population. We compared younger (18-24 years old) and older (≥25 years old) HIV-infected pregnant women initiating antiretroviral therapy (ART) in Cape Town, South Africa. Women were assessed on a range of psychosocial measures, including the Alcohol Use Disorders Identification Test and the Edinburgh Postnatal Depression Scale (EPDS). Among 625 women initiating ART, 16 % reported risky alcohol use and 21 % alcohol-related harm; these percentages were similar across age groups. When younger women were stratified by age, 37 % of 18-21 years old versus 20 % of 22-24 years old reported alcohol-related harm (p = 0.02). Overall, 11 % of women had EPDS scores suggesting probable depression, and 6 % reported self-harming thoughts. Younger women reported more depressive symptoms. Report of self-harming thoughts was 11 % in younger and 4 % in older women (p = 0.002). In multivariable analysis, age remained significantly associated with depressive symptoms and report of self-harming thoughts. Level of HIV-related stigma and report of intimate partner violence modified the association between age and depressive symptoms. Young HIV-infected pregnant women in South Africa were more likely to report depressive symptoms and self-harming thoughts compared to older women, and the youngest women reported the highest levels of alcohol-related harm. HIV-related stigma and intimate partner violence may be moderating factors. These findings have implications for maternal and infant health, underscoring the urgent need for effective targeted interventions in this vulnerable population.

Data suggest that pregnant women in some settings have high prevalence of HIV and other sexually transmitted infections (STI). We examined changes in sexual risk behaviors and intravaginal practices during pregnancy that may contribute to HIV and STI incidence using data from the Methods for Improved Reproductive Health in Africa study conducted in South Africa and Zimbabwe 2003–2006. We used a crossover design and modified Poisson regression to compare behaviors among HIV negative women 18–45 years during pregnant and non-pregnant periods. Among the 4802 women

Context HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. Objective We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. Methods As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal–social. Results Median age pre-ART was 8.8 months (range 2.2–24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9–14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal–social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). Conclusion Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes.

Adolescents account for 40% of new HIV infections, and HIV testing strategies to increase uptake of testing are needed. A community-based adolescent and youth HIV and health testing campaign was conducted in seven slum neighborhoods of Port-au-Prince, Haiti, from December 2014 to September 2015. Community health workers provided community sensitization and recruited 10- to 24-year-olds to test for HIV, syphilis, gonorrhea/chlamydia, and to screen for tuberculosis (TB) and pregnancy. HIV-infected individuals were escorted to the GHESKIO HIV clinic for same-day enrollment in care. Among 3425 individuals eligible for testing, 3348 (98%) accepted an HIV test. HIV prevalence was 2.65% (n = 89). Median age was 19 [interquartile range (IQR) 17-20]; 73% were female. HIV prevalence was 0.6-7.4% across slum neighborhoods. All HIV-infected individuals enrolled in care the same day as testing; median CD4 was 529 cells/μL [IQR 363-761]. Syphilis prevalence was 2.60% (65/2536) and gonorrhea/chlamydia prevalence was 6.25% (96/1536). Among 168 (5%) individuals who reported TB symptoms, 7.7% (13/168) had microbiologically confirmed disease. One hundred twenty-nine females (5% of all females) were pregnant. This community-based testing campaign identified an adolescent and youth population with an HIV prevalence six times higher than the estimated national adolescent HIV prevalence (0.4%) in Haiti, including perinatally infected adolescents. This type of community-based campaign for HIV testing within a package of services can serve as a model for other resource-poor settings to identify high-risk adolescents and youth, and curb the global HIV epidemic among adolescents.

Objectives Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. Methods We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. Results A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL 1000 copies/mL at delivery, respectively (P < 0.001). Conclusions High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

Depression, HIV-related stigma and low levels of social support may be particularly prevalent and adversely affect health and treatment outcomes among HIV-infected pregnant women. We examined factors associated with social support and stigma among pregnant women initiating antiretroviral therapy in the Western Cape, South Africa; and explored associations with depressive symptoms (Edinburgh Postnatal Depression Scale; EPDS) in linear regression models. Among 623 participants, 11 and 19 % had elevated EPDS scores using thresholds described in the original development of the scale (scores ≥13 and ≥10, respectively). Social support and stigma were highly interrelated and were associated with depressive symptoms. Stigma was observed to moderate the association between social support and depression scores; when levels of stigma were high, no association between social support and depression scores was observed. Elevated depression scores are prevalent in this setting, and interventions to reduce stigma and to address risk factors for depressive symptoms are needed.

Background Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. Methods Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. Results The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4–5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8–527.4]). Based on these findings, we estimate that 90% attributable to ART nonadherence. Conclusions DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

BACKGROUND Estimates of incidence of switching to second-line antiretroviral therapy (ART) among children with HIV are necessary to inform the need for paediatric second-line formulations. We aimed to quantify the cumulative incidence of switching to second-line ART among children in an international cohort collaboration. METHODS In this international cohort collaboration study, we pooled individual patient-level data for children younger than 18 years who initiated ART (two or more nucleoside reverse-transcriptase inhibitors [NRTI] plus a non-NRTI [NNRTI] or boosted protease inhibitor) between 1993 and 2015 from 12 observational cohort networks in the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration. Patients who were reported to be horizontally infected with HIV and those who were enrolled in trials of treatment monitoring, switching, or interruption strategies were excluded. Switch to second-line ART was defined as change of one or more NRTI plus either change in drug class (NNRTI to protease inhibitor or vice versa) or protease inhibitor change, change from single to dual protease inhibitor, or addition of a new drug class. We used cumulative incidence curves to assess time to switching, and multivariable proportional hazards models to explore patient-level and cohort-level factors associated with switching, with death and loss to follow-up as competing risks. FINDINGS At the data cutoff of Sept 16, 2015, 182 747 children with HIV were included in the CIPHER dataset, of whom 93 351 were eligible, with 83 984 (90·0%) from sub-Saharan Africa. At ART initiation, the median patient age was 3·9 years (IQR 1·6-6·9) and 82 885 (88·8%) patients initiated NNRTI-based and 10 466 (11·2%) initiated protease inhibitor-based regimens. Median duration of follow-up after ART initiation was 26 months (IQR 9-52). 3883 (4·2%) patients switched to second-line ART after a median of 35 months (IQR 20-57) of ART. The cumulative incidence of switching at 3 years was 3·1% (95% CI 3·0-3·2), but this estimate varied widely depending on the cohort monitoring strategy, from 6·8% (6·5-7·2) in settings with routine monitoring of CD4 (CD4% or CD4 count) and viral load to 0·8% (0·6-1·0) in settings with clinical only monitoring. In multivariable analyses, patient-level factors associated with an increased likelihood of switching were male sex, older age at ART initiation, and initial NNRTI-based regimen (p

Purpose: The use of cumulative measures of exposure to raised HIV viral load (viremia copy-years) is an increasingly common in HIV prevention and treatment epidemiology due to the high biological plausibility. We sought to estimate the magnitude and direction of bias in a cumulative measure of viremia caused by different frequency of sampling and duration of follow-up. Methods: We simulated longitudinal viral load measures and reanalysed cohort study datasets with longitudinal viral load measurements under different sampling strategies to estimate cumulative viremia. Results: In both simulated and observed data, estimates of cumulative viremia by the trapezoidal rule show systematic upward bias when there are fewer sampling time points and/or increased duration between sampling time points, compared to estimation of full time series. Absolute values of cumulative viremia vary appreciably by the patterns of viral load over time, even after adjustment for total duration of follow up. Conclusions: Sampling bias due to differential frequency of sampling appears extensive and of meaningful magnitude in measures of cumulative viremia. Cumulative measures of viremia should be used only in studies with sufficient frequency of viral load measures and always as relative measures., 16 pages, 2 figures, 3 tables

Objective Unintended pregnancies are common among women living with HIV, but there are no data on their long-term impact on treatment outcomes. In a cohort of women initiating antiretroviral therapy (ART) during pregnancy, we examined the association between the intendedness of the current pregnancy, measured antenatally, and elevated viral load up to 5 years postpartum. Design Prospective study with enrolment at entry into antenatal care and follow-up at study visits separate from routine care. Methods At enrolment women completed the London Measure of Unplanned Pregnancy. Mixed effects models examined the impact of the intendedness of the pregnancy (planned versus each of unplanned or ambivalent, respectively) on viral load 50 or more copies/ml across postpartum study visits. Results Overall, 459 women were followed for a median of 43 months postpartum, contributing 2535 viral load measures (median per woman: 6). Ambivalent and unplanned pregnancy were commonly reported (20 and 60%, respectively), and the proportion of women with elevated viral load increased over time (16% at 6 weeks to 43% by 36-60 months postpartum). Compared with those reporting a planned pregnancy, elevated viral load was more common among women reporting an unplanned pregnancy (odds ratio: 2.87; 95% confidence interval: 1.46-5.64), with a trend towards a higher odds among those reporting ambivalence (odds ratio: 2.19; 95% confidence interval: 0.97-4.82); associations persisted after adjustment for a wide range of demographic, clinical and psychosocial factors. Conclusion These novel data suggest that unplanned pregnancy may be a prevalent and persistent predictor of poor ART outcomes among women initiating ART during pregnancy.