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Item does not contain fulltext Although 23 antiretroviral drugs are approved for use in adults, only six are approved by regulatory authorities for use in term neonates born to women with HIV, with even fewer options for preterm neonates. A major hurdle for approvals is the delay in the generation of pharmacokinetic and safety data for antiretrovirals in neonates. The median time between the year of approval from the US Food and Drug Administration of an antiretroviral agent for adults and the first publication date for pharmacokinetic data in neonates less than 4 weeks old is 8 years (range 2-23 years). In this Viewpoint, we address pharmacokinetic research gaps and priorities for current and novel antiretroviral use in neonates. We also consider the challenges and provide guidance on neonatal clinical pharmacology research on antiretroviral agents with the goal of stimulating research and expediting the availability of safe medications for the prevention and treatment of HIV in this vulnerable population.

Background Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure but uninfected (HEU) compared to those perinatally HIV unexposed and uninfected (HUU). Methods We enrolled pregnant persons with HIV (PWH) receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir (DTG) or efavirenz (EFV), and pregnant individuals without HIV, as well as their liveborn infants. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Preprandial homeostasis model assessment for insulin resistance (HOMA-IR) was assessed at birth and 1 month. Linear mixed models were fit to assess the association between in utero HIV/ARV exposure and average HOMA-IR from birth to 1 month, adjusting for confounders. Results Of 450 newborns, 306 were HEU. HOMA-IR was higher in newborns HEU versus HUU after adjusting for confounders (mean difference of 0.068 in log HOMA-IR, P = .037). Among newborns HEU, HOMA-IR was not significantly different between TDF/XTC/DTG versus TDF/XTC/EFV in utero ARV exposure and between AZT versus NVP newborn postnatal prophylaxis arms. Conclusions Newborns HEU versus HUU had lower insulin sensitivity at birth and at 1 month of life, raising potential concern for obesity and other metabolic perturbations later in life for newborns HEU. Clinical Trials Registration NCT03088410.

Background In Mozambique, HIV infection remains a leading cause of adolescent mortality. With advances in antiretroviral treatment (ART), the population of adolescents living with vertically-acquired HIV is growing. Most studies of adolescents living with HIV (ALHIV) focus on older youth with horizontal infection. As part of a larger study, we examined the characteristics and health care needs of younger ALHIV, including those with vertically-acquired infection to inform preventive interventions. Methods We used a convergent mixed-methods design and recruited ALHIV aged 12–14 years who were enrolled in HIV care in three health clinics in Nampula, Mozambique. From 11/2019–3/2020, we conducted 61 quantitative surveys and 14 in-depth interviews with a purposively selected subset of ALHIV who were aware of their HIV status. Descriptive statistical analysis was conducted for quantitative data. Qualitative data were transcribed and analyzed using thematic analysis. Results The median age of ALHIV was 13 years, 50% were female, 67% lived with ≥1 parent, 70% had lost a parent, 100% were in school; 10% were in a relationship, and 3% had initiated sexual activity. Among 31 ALHIV aware of their serostatus, the median age of antiretroviral treatment (ART) initiation was 8 years (IQR: 6–11); 55% received caregiver support for ART management; 35% reported missing ≥1 ART dose in the last 30 days; 6% had disclosed their HIV-status to friends and 48% reported no one to talk to about HIV-specific issues. Four main themes emerged from the qualitative interviews with ALHIV: a) learning one’s HIV-positive status as the beginning of a secret life; b) importance of caregivers’ support for ART management; c) high value of ALHIV peer support to overcome isolation, increase HIV literacy, and support adherence; and d) unmet needs for sexual and reproductive health education. Conclusion HIV-related secrecy prevails among ALHIV, a situation exacerbated by caregivers and healthcare providers. Caregivers play a major role in supporting adherence among young ALHIV, yet ALHIV could also benefit from adolescent-friendly services, including peer support, sexual and reproductive health services and preparation for independent health management. Integrating such programs into ART services in Mozambique may be critical to promoting ALHIV health.

Globally, non-communicable diseases (NCDs) or chronic conditions account for one-third of disability-adjusted life-years among children and adolescents under the age of 20. Health systems must adapt to respond to the growing burden of NCDs among children and adolescents who are more likely to be marginalised from healthcare access and are at higher risk for poor outcomes. We undertook a review of recent literature on existing models of chronic lifelong care for children and adolescents in low-income and middle-income countries with a variety of NCDs and chronic conditions to summarise common care components, service delivery approaches, resources invested and health outcomes.

BACKGROUND Suicide is a leading cause of death among adolescents and young adults (AYA). AYA living with perinatally acquired HIV infection (AYALPHIV) are at higher risk of attempted suicide when compared with AYA who were perinatally HIV-exposed but uninfected (AYAPHEU). To inform interventions, we identified risk and protective factors of attempted suicide among AYALPHIV and AYAPHEU. SETTING Data were obtained from a longitudinal New York City-based study of AYALPHIV and AYAPHEU (n = 339; enrollment age 9-16 years) interviewed approximately every 12-18 months. METHOD Our main outcome was suicide attempt at any follow-up. The DISC was used to assess psychiatric disorder diagnoses and attempted suicide and the Child Depression Inventory to assess depressive symptoms. Psychosocial and sociodemographic risk factors were also measured. Analyses used backward stepwise logistic regression modeling. RESULTS At enrollment, 51% was female individuals, 49% Black, 40% Latinx, and 11% both Black and Latinx. Attempted suicide prevalence was significantly higher among AYALPHIV compared with AYAPHEU (27% vs 16%, P = 0.019), with AYALPHIV having 2.21 times the odds of making an attempt [95% confidence interval: (1.18 to 4.12), P = 0.013]. Higher Child Depression Inventory scores were associated with an increased risk of attempted suicide in both groups and the total sample. The presence of DISC-defined behavior disorder increased the risk of attempted suicide in the total sample and the AYALPHIV subgroup. Religiosity was protective of attempted suicide in AYALPHIV. CONCLUSIONS AYALPHIV had increased suicide attempts compared with AYAPHEU. Religiosity was protective in AYALPHIV. Highlighting a need for prevention of early mental health challenges was associated with risk.

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.

Despite considerable progress in paediatric HIV treatment and timely revision of global policies recommending the use of more effective and tolerable antiretroviral regimens, optimal antiretroviral formulations for infants, children, and adolescents remain limited. The Paediatric Antiretroviral Drug Optimization group reviews medium-term and long-term priorities for antiretroviral drug development to guide industry and other stakeholders on formulations most needed for low-income and middle-income countries. The group convened in December, 2018, to assess progress since the previous meeting and update the list of priority formulations. Issues relating to drug optimisation for neonatal prophylaxis and paediatric treatment, and those relating to the investigation of novel antiretrovirals in adolescents and pregnant and lactating women were also discussed. Continued focus on identifying, prioritising, and providing access to optimal antiretroviral formulations suitable for infants, children, and adolescents is key to ensuring that global HIV treatment targets can be met.

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.

Perinatally-acquired HIV has persistent effects on long-term health outcomes, even after early treatment. We hypothesize that epigenetic indicators, such as DNA methylation, may elucidate cellular processes that explain these effects. Here, we compared DNA methylation profiles in whole blood from 120 HIV-infected children on antiretroviral therapy (ART) and 60 frequency age-matched HIV-uninfected children aged 4–9 years in Johannesburg, South Africa. Using an individual CpG site approach, we found 1,309 differentially-methylated (DM) CpG sites between groups, including 1,271 CpG sites that were hyper-methylated in the HIV-infected group and 38 CpG sites that were hypo-methylated in the HIV-infected group. Six hyper-methylated CpG sites were in EBF4, which codes for a transcription factor involved in B-cell maturation. The top hypomethylated site was in the promoter region of NLRC5, encoding a transcription factor that regulates major histocompatibility complex (MHC) class I molecule expression. Using a differentially-methylated region (DMR) approach, we found 315 DMRs between groups, including 28 regions encompassing 686 CpG sites on chromosome 6. A large number of the genes identified in both the CpG site and DMR approaches were located in the MHC region on chromosome 6, which plays an important role in the adaptive immune system. This study provides the first evidence that changes in the epigenome are detectable in children with perinatally-acquired HIV infection on suppressive ART started at an early age.

Factors that influence viral response when antiretroviral therapy (ART) is initiated in neonates are not well characterized. We assessed if there is consistency in predictive factors when operationalizing viral response using different methods. Data were collected from a clinical study in South Africa that started ART in neonates within 14 days of birth (2013–2018). Among 61 infants followed for ≥48 weeks after ART initiation, viral response through 72 weeks was defined by three methods: (1) clinical endpoints (virologic success, rebound, and failure), (2) time to viral suppression, i.e., any viral load (VL: copies/mL) &lt, 400, &lt, 50, or target not detected (TND) using time-to-event methods, and (3) latent class growth analysis (LCGA) to empirically estimate discrete groups with shared patterns of VL trajectories over time. We investigated the following factors: age at ART initiation, sex, birthweight, preterm birth, mode of delivery, breastfeeding, pre-treatment VL and CD4, maternal ART during pregnancy, and maternal VL and CD4 count. ART was initiated 0–48 h of birth among 57.4% of the infants, 48 h–7 days in 29.5% and 8–14 days in 13.1%. By Method 1, infants were categorized into ‘success’ (54.1%), ‘rebound’ (21.3%), and ‘failure’ (24.6%) for viral response. For Method 2, median time to achieving a VL &lt, 50, or TND was 58, 123, and 331 days, respectively. For Method 3, infants were categorized into three trajectories: ‘rapid decline’ (29.5%), ‘slow decline’ (47.5%), and ‘persistently high’ (23.0%). All methods found that higher pre-treatment VL, particularly &gt, 100,000, was associated with less favorable viral outcomes. No exposure to maternal ART was associated with a better viral response, while a higher maternal VL was associated with less favorable viral response and higher maternal CD4 was associated with better viral response across all three methods. The LCGA method found that infants who initiated ART 8–14 days had less favorable viral response than those who initiated ART earlier. The other two methods trended in a similar direction. Across three methods to operationalize viral response in the context of early infant treatment, findings of factors associated with viral response were largely consistent, including infant pre-treatment VL, maternal VL, and maternal CD4 count.

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.

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.

International audience; Ameena Goga and colleagues argue that frequent testing of maternal viral load is needed to eliminate HIV transmission through breast milk in low and middle income settings

HIV+ South African women who achieved viral suppression during routine antenatal care, but later experienced a viremic episode (viral load >1000 copies/mL), were examined for presence of antiretrovirals and classified as “nonadherers” or “suboptimal adherers.” Women were tested for drug resistance mutations (DRMs) at several time points and underwent viral load testing 36–60 months postpartum. Suboptimal adherers were more likely to have DRM detected during their viremic episode (P = .03) and at a subsequent viremic time point (P = .05). There was no difference in levels of viral suppression 36–60 months later in women with DRM detected vs women who had no evidence of DRM (P = .5).

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.

Introduction We previously found lower bone mass but similar bone turnover in pre-pubertal children living with HIV (CLWH) on a ritonavir-boosted lopinavir (LPV/r)-based vs. efavirenz-based antiretroviral therapy regimen 2 years after switch. Here, we evaluate if bone turnover differed between the groups close to the time of switch. Methods Samples from 108 children remaining on LPV/r and 104 children switched to efavirenz were available for analysis 8 weeks post-randomization. Bone turnover markers, including C-telopeptide of type 1 collagen (CTx), procollagen type-I N-terminal propeptide (P1NP), and osteocalcin were measured. Markers of immune activation were also measured, including IL-6, TNF-alpha, soluble CD14 and high-sensitivity C-reactive protein (CRP). Results Eight weeks post-randomization, we did not detect differences in CTx (1.42 vs. 1.44 ng/mL, p = 0.85) or P1NP concentrations (622 vs. 513 ng/mL, p = 0.68) between treatment groups. At 8 weeks, the treatment groups also had similar levels of IL-6, TNF-alpha, soluble CD14 and high-sensitivity CRP. Osteocalcin (ng/mL) was higher in the LPV/r than efavirenz group both at 8 weeks (88.6 vs. 67.3, p = 0.001) and 2 years (67.6 vs. 49.8, p = 0.001). Conclusions Overall, we failed to detect difference in bone turnover by P1NP and CTx in virologically-suppressed CLWH on different regimens at a time point close to the switch. We did observe higher levels of total osteocalcin in children remaining on LPV/r compared to children switched to efavirenz. Future studies should focus on uncovering the mechanism and determining whether perturbation in undercarboxylated osteocalcin could explain some of the bone side effects noted with protease inhibitors.

BACKGROUND Younger age at antiretroviral therapy (ART) initiation has been associated with smaller HIV reservoirs. We investigated whether younger age of ART initiation is associated with testing negative and weaker signal on a standard HIV diagnostic test in treated children. METHODS At exit from a longitudinal study at 2 sites in Johannesburg, South Africa, 316 school-aged, HIV-infected children on continuous ART started at a median age of 6.3 months, were tested with standard total nucleic acid PCR used for infant diagnosis. All negative results were repeated. Simultaneous viral load (VL) and CD4 T-cell counts/percentages, along with data collected over the prior 4 years, were used in multivariable regression to predict negative PCR results and higher cycle threshold (Ct) values (weaker signal). RESULTS Seven children (2.2%, 95% confidence interval: 0.6 to 3.8) in the full cohort had negative PCR results; all 7 were in a subset of 102 (6.9%, 95% confidence interval: 2.0 to 11.8) who had initiated ART at age 0-4 months and had VL

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.Two HIV-exposed infants in Johannesburg, South Africa were identified presenting with unusual trajectories of diagnostic nucleic acid amplification tests (NAAT) and viral load results.Case 1 had repeat indeterminate NAAT results during the first 3 weeks of life; repeat testing thereafter was negative with undetectable viral load including after daily nevirapine prophylaxis ended. ART was not initiated at this time. Case 2 had a single positive NAAT result at 1 month of age that prompted initiation of ART. Subsequent results were negative and ART was discontinued. Repeat negative NAAT with viral load below the limit of quantification or undetectable continued to be obtained. Shortly after and around weaning, positive NAAT results with high viral load (7.1 and 6.03 log10 copies/ml for Cases 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.We hypothesize that breast milk from the mothers of these two rare cases had HIV-specific or nonspecific 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 breast-fed infants after complete cessation of all breastfeeding.

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.

Background: Studies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some. Methods: We designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART 30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART

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.

BackgroundPoor engagement in postpartum maternal HIV care is a challenge worldwide and contributes to adverse maternal outcomes and vertical transmission. Our objective was to project the clinical and economic impact of integrated postpartum maternal antiretroviral therapy (ART) and pediatric care in South Africa.MethodsUsing the CEPAC computer simulation models, parameterized with data from the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) randomized controlled trial, we evaluated the cost-effectiveness of integrated postpartum care for women initiating ART in pregnancy and their children. We compared two strategies: 1) standard of care (SOC) referral to local clinics after delivery for separate standard ART services for women and pediatric care for infants, and 2) the MCH-ART intervention (MCH-ART) of co-located maternal/pediatric care integrated in Maternal and Child Health (MCH) services throughout breastfeeding. Trial-derived inputs included: 12-month maternal retention in care and virologic suppression (SOC: 49%, MCH-ART: 67%), breastfeeding duration (SOC: 6 months, MCH-ART: 8 months), and postpartum healthcare costs for mother-infant pairs (SOC: $50, MCH-ART: $69). Outcomes included pediatric HIV infections, maternal and infant life expectancy (LE), lifetime HIV-related per-person costs, and incremental cost-effectiveness ratios (ICERs; ICER ResultsCompared to SOC, MCH-ART increased maternal LE (SOC: 25.26 years, MCH-ART: 26.20 years) and lifetime costs (SOC: $9,912, MCH-ART: $10,207; discounted). Projected pediatric outcomes for all HIV-exposed children were similar between arms, although undiscounted LE for HIV-infected children was shorter in SOC (SOC: 23.13 years, MCH-ART: 23.40 years). Combining discounted maternal and pediatric outcomes, the ICER was $599/YLS.ConclusionCo-located maternal HIV and pediatric care, integrated in MCH services throughout breastfeeding, is a cost-effective strategy to improve maternal and pediatric outcomes and should be implemented in South Africa.

The global population of perinatally HIV-exposed but uninfected (HEU) children is growing, with relatively little known about their psychosocial outcomes, particularly across adolescence and young adulthood. Using data from a longitudinal cohort study of HEU youth in New York City (N=134), we examine rates of substance use disorders (SUD) and non-SUD psychiatric disorders (mood, anxiety, and behavioral) at five time-points during adolescence and young adulthood, as well as associated demographic and environmental factors and the association of ever having a disorder with young adult developmental milestones. HEU participants in this study experienced high rates of psychiatric disorders, particularly SUD in young adulthood. During the entire study period (2003-2018), over one third were diagnosed at least once with a SUD, and 69% were diagnosed with a non-SUD psychiatric disorder. Older age and female gender were associated with higher rates of non-SUD diagnoses. A history of meeting criteria for any disorder at any time point was associated with reduced odds in young adulthood of working or being in school and increased odds of reporting incarceration, homelessness, and recent condomless sex. There is an urgent need to develop systems to follow HEU youth and provide services to intervene and treat psychiatric disorders, including substance use.

ContextHigh rates of burnout have been reported in low and medium income countries and can detrimentally impact healthcare delivery. Understanding factors associated with burnout amongst health care workers providing HIV care may help develop interventions to prevent/treat burnout.ObjectivesWe sought to understand factors associated with burnout amongst health care workers providing HIV care in Malawi.MethodsThis was a sub-study of a larger cross-sectional study measuring burnout prevalence amongst a convenience sample of healthcare workers providing HIV care in 89 health facilities in eight districts in Malawi. Burnout was measured using the Maslach Burnout Inventory. Anonymously administered surveys included questions about sociodemographics, work characteristics (work load, supervisor support, team interactions), depression, life stressors, assessment of type D personality, and career satisfaction. We performed univariable and multivariable regression analyses to explore associations between variables and burnout.ResultsWe received 535 responses (response rate 99%). Factors associated with higher rates of burnout on multivariable regression analyses included individual level factors: male gender (OR 1.75 [CI 1.17, 2.63]; p = 0.007), marital status (widowed or divorced) (OR 3.24 [CI 1.32, 7.98]; p = 0.011), depression (OR 3.32 [CI 1.21, 9.10]; p = 0.020), type D personality type (OR 2.77 [CI 1.50, 5.12]; p = 0.001) as well as work related factors: working at a health center vs. a rural hospital (OR 2.02 [CI 1.19, 3.40]; p = 0.009); lack of a very supportive supervisor (OR 2.38 [CI 1.32, 4.29]; p = 0.004), dissatisfaction with work/team interaction (OR 1.76 [CI 1.17, 2.66]; p = 0.007), and career dissatisfaction (OR 0.76 [CI 0.60, 0.96]; p = 0.020).ConclusionThis study identified several individual level vulnerabilities as well as work related modifiable factors. Improving the supervisory capacity of health facility managers and creating conditions for improved team dynamics may help reduce burnout amongst healthcare workers proving HIV care in Malawi.