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Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.

: Introduction: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. Methods: We analysed data from people living with HIV (aged 15–49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan–Meier curves and proportional‐hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. Results: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25–27%) had disengaged from care by 1 year and 34% (95% CI 33–36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70–2.60), restarted (C: aHR 3.32, 95% CI 2.70–4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12–2.74) had increased hazards of postpartum disengagement compared to those on ART (A). Conclusions: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care., INTRODUCTION Although antiretroviral therapy (ART) is recommended for all people living with HIV (PLHIV), major challenges persist with engagement in care [1, 2]. For pregnant PLHIV, the benefits of lifelong [...]

Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context.

IntroductionHIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout.MethodsWe used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women.Results and discussionWe identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation.ConclusionsExpanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.

A growing number of low- and middle-income country (LMIC) institutions have developed and implemented formal programs to support mentorship. Although the individual-level benefits of mentorship are well established, such activities can also sustainably build institutional capacity, bridge inequities in health care, and catalyze scientific advancement. To date, however, evaluation of these programs remains limited, representing an important gap in our understanding about the impact of mentoring. Without rigorous and ongoing evaluation, there may be missed opportunities for identifying best practices, iteratively improving program activities, and demonstrating the returns on investment in mentorship. In this report, we propose a framework for evaluating mentorship programs in LMIC settings where resources may be constrained. We identify six domains: 1) mentor-mentee relationship, 2) career guidance, 3) academic productivity, 4) networking, 5) wellness, and 6) organizational capacity. Within each, we describe specific metrics and how they may be considered as part of evaluation plans. We emphasize the role of measurement and evaluation at the institutional level, so that programs may enhance their mentoring capacity and optimize the management of their resources. Although we advocate for a comprehensive approach to evaluation, we recognize that-depending on stage and relative maturity-some domains may be prioritized to address short- and medium-term program goals.

Mentoring is a proven path to scientific progress, but it is not a common practice in low- and middle-income countries (LMICs). Existing mentoring approaches and guidelines are geared toward high-income country settings, without considering in detail the differences in resources, culture, and structure of research systems of LMICs. To address this gap, we conducted five Mentoring-the-Mentor workshops in Africa, South America, and Asia, which aimed at strengthening the capacity for evidence-based, LMIC-specific institutional mentoring programs globally. The outcomes of the workshops and two follow-up working meetings are presented in this special edition of the American Journal of Tropical Medicine and Hygiene. Seven articles offer recommendations on how to tailor mentoring to the context and culture of LMICs, and provide guidance on how to implement mentoring programs. This introductory article provides both a prelude and executive summary to the seven articles, describing the motivation, cultural context and relevant background, and presenting key findings, conclusions, and recommendations.

Background: Persistent hypertension is common after preeclampsia and is causally tied to later cardiovascular risks. This study examined whether being HIV-infected and on antiretroviral therapy (ART) is associated with persistent postpartum hypertension among women diagnosed with preeclampsia. Methods: We conducted a six-month prospective cohort study at Kanyama and Women and Newborn hospitals from January 01, 2022, to June 30, 2023, among 190 women diagnosed with preeclampsia (59 HIV-positive, 131 HIV-negative). Sociodemographic and clinical characteristics were collected at delivery, six weeks, three months and six months after giving birth. Persistent hypertension was diagnosed if a participant presented with elevated blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg and/or taking medication for hypertension at the study visit. We used a generalized estimating equation to describe the relationship between treated HIV and persistent hypertension six months following delivery. Results: We retained 136 participants (71.6%) to six months postpartum, at a median age of 30 years. Overall, persistent hypertension at six weeks, three months, and six months postpartum was common (37.4%, 17.1% and 16.9%, respectively). Six-week postpartum prevalence was higher in the HIV group than HIV-negative group (54.6% vs 28.8%, p<0.001), with no measurable difference at three months (24.3% vs 13.2%, p = 0.145) or six months (18.2% vs 16.3%, p = 0.787). Multivariable analysis demonstrates higher odds (adjusted odds ratio [aOR] = 1.68, 95% CI: 1.09–2.60) of persistent hypertension among the HIV+treatment group than HIV-negative counterparts after accounting for age, body mass index and time since delivery. Conclusion: We demonstrate an elevated risk of persistent hypertension among postpartum women with comorbid preeclampsia and treated HIV. Peripartum patients in HIV-endemic settings may benefit from timely detection of hypertension and treatment interventions to improve health outcomes. [ABSTRACT FROM AUTHOR]

: Introduction: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence. Methods: We constructed a multi‐state model describing male‐to‐female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re‐initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre‐exposure prophylaxis (PrEP) for HIV‐negative female ANC patients with HIV‐diagnosed or unknown‐status male partners. We estimated the percentage of within‐couple, male‐to‐female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base‐case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re‐initiate ART and 0% of female ANC patients start PrEP. Results: Increasing uptake of any single strategy by 20 percentage points above base‐case levels averted 10%−11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%−23% of transmissions, and with a 20‐percentage‐point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re‐initiation and 40% female PrEP use reduced incident infections by 45%. Conclusions: Combination HIV prevention strategies provided alongside ANC and sustained through the post‐partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa., INTRODUCTION The rising uptake of lifelong antiretroviral therapy (ART) among pregnant people living with HIV and attending antenatal care (ANC) resulted in a 38% reduction in vertical HIV transmission between [...]

Introduction: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. Discussion: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. Conclusions: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and well being of pregnant people and their children. Keywords: co-infections; ethics; HIV; pregnancy; prevention; research, 1 | INTRODUCTION Since the early 1990s, the management of pregnancy has been an important focus for HIV research. The urgent need to identify interventions to prevent perinatal transmission led [...]

BackgroundRandomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.MethodsWe randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety.ResultsThe median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P

As demand for global health research training continues to grow, many universities are striving to meet the needs of trainees in a manner complementary to research priorities of the institutions hosting trainees, while also increasing capacity for conducting research. We provide an overview of the first 4 years of the Global Health Program for Fellows and Scholars, a collaboration of 20 U.S. universities and institutions spread across 36 low- and middle-income countries funded through the National Institutes of Health Fogarty International Center. We highlight many aspects of our program development that may be of interest to other multinational consortia developing global health research training programs.

Introduction: Findings from biomedical, behavioural and implementation studies provide a rich foundation to guide programmatic efforts for the prevention of mother-to-child HIV transmission (PMTCT). Methods: We summarized the current evidence base to support policy makers, programme managers, funding agencies and other stakeholders in designing and optimizing PMTCT programmes. We searched the scientific literature for PMTCT interventions in the era of universal antiretroviral therapy for pregnant and breastfeeding women (i.e. 2013 onward). Where evidence was sparse, relevant studies from the general HIV treatment literature or from prior eras of PMTCT programme implementation were also considered. Studies were organized into six categories: HIV prevention services for women, timely access to HIV testing, timely access to ART, programme retention and adherence support, timely engagement in antenatal care and services for infants at highest risk of HIV acquisition. These were mapped to specific missed opportunities identified by the UNAIDS Spectrum model and embedded in UNICEF operational guidance to optimize PMTCT services. Results and discussion: From May to November 2019, we identified numerous promising, evidence-based strategies that, properly tailored and adopted, could contribute to population reductions in vertical HIV transmission. These spanned the HIV and maternal and child health literature, emphasizing the importance of continued alignment and integration of services. We observed overlap between several intervention domains, suggesting potential for synergies and increased downstream impact. Common themes included integration of facility-based healthcare; decentralization of health services from facilities to communities; and engagement of partners, peers and lay workers for social support. Approaches to ensure early HIV diagnosis and treatment prior to pregnancy would strengthen care across the maternal lifespan and should be promoted in the context of PMTCT. Conclusions: A wide range of effective strategies exist to improve PMTCT access, uptake and retention. Programmes should carefully consider, prioritize and plan those that are most appropriate for the local setting and best address existing gaps in PMTCT health services. Keywords: HIV prevention; children; elimination of mother-to-child transmission; prevention of mother-to-child transmission; globa, 1 | INTRODUCTION Significant achievements have been made in the prevention of mother-to-child HIV transmission (PMTCT), transforming the paediatric HIV epidemic globally. With new innovations, strong political will and rapid [...]

Introduction: HIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout. Methods: We used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women. Results and discussion: We identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation. Conclusions: Expanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy. Keywords: preexposure prophylaxis; PrEP; pregnancy; breastfeeding; PMTCT; prevention of mother to child transmission; HIV, 1 | INTRODUCTION HIV incidence is high during pregnancy and breastfeeding [1] with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are [...]

Tremendous gains have been made in the prevention of mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Ambitious goals for the "virtual elimination" of pediatric HIV appear increasingly feasible, driven by new scientific advances, forward-thinking health policy, and substantial donor investment. To fulfill this promise, however, rapid and effective implementation of evidence-based practices must be brought to scale across a diversity of settings. The discipline of implementation research can facilitate this translation from policy into practice; however, to date, its core principles and frameworks have been inconsistently applied in the field. We reviewed the recent developments in implementation research across each of the four "prongs" of a comprehensive PMTCT approach. While significant progress continues to be made, a greater emphasis on context, fidelity, and scalability-in the design and dissemination of study results-would greatly enhance current efforts and provide the necessary foundation for future evidence-based programs.

: Introduction: Pregnant women are routinely excluded from clinical trials, leading to the absence or delay in even the most basic pharmacokinetic (PK) information needed for dosing in pregnancy. When available, pregnancy PK studies use a small sample size, resulting in limited safety information. We discuss key study design elements that may enhance the timely availability of pregnancy data, including the role and timing of randomized controlled trials (RCTs) to evaluate pregnancy safety; efficacy and safety outcome measures; stand‐alone protocols, platform trials, single arm studies, sample size and the effect that follow‐up time during gestation has on analysis interpretations; and observational studies. Discussion: Pregnancy PK should be studied during drug development, after dosing in non‐pregnant persons is established (unless non‐clinical or other data raise pregnancy concerns). RCTs should evaluate the safety during pregnancy of priority new HIV agents that are likely to be used by large numbers of females of childbearing age. Key endpoints for pregnancy safety studies include birth outcomes (prematurity, small for gestational age and stillbirth) and neonatal death, with traditional adverse events and infant growth also measured (congenital anomalies are best studied through surveillance). We recommend that viral efficacy be studied as a secondary endpoint of pregnancy RCTs, once PK studies confirm adequate drug exposure in pregnancy. RCTs typically use a stand‐alone protocol for new agents. In contrast, master protocols using a platform design can add agents over time, possibly speeding safety data ascertainment. To speed accrual, stand‐alone pregnancy trial protocols can include pre‐specified starting rules based upon adequate PK levels in pregnancy; and seamless master protocols or platform trials can include a pregnancy PK and safety component. When RCTs are unethical or cost‐prohibitive, observational studies should be conducted, preferably using target trial emulation to avoid bias. Conclusions: Pregnancy PK needs to be obtained earlier in drug evaluation. Timely RCTs are needed to understand safety in pregnancy for high‐priority new HIV agents. RCTs that enrol pregnant women should focus on outcomes unique to pregnancy, and observational studies should focus on questions that RCTs are not equipped to answer., INTRODUCTION Pregnancy and lactation data are lacking for more than 90% of Food and Drug Administration (FDA)‐approved drugs [1], and pregnant/breastfeeding women are routinely excluded from pre‐ and post‐licensure clinical [...]

BackgroundAlthough patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition.Methods and findingsAt a set "status classification" date, patients were categorized as either "active" or "LTFU" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%).ConclusionsBased on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary.

Background In sub-Saharan Africa, 3 community-facility linkage (CFL) models-Expert Clients, Community Health Workers (CHWs), and Mentor Mothers-have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood. Methods and findings We sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant 'poor outcome' (encompassing documented HIV-positive test result, LTFU, or death), in Malawi's PMTCT/ART program. We sampled 30 of 42 high-volume health facilities ('sites') in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother-infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother-infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were [less than or equal to]24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) [greater than or equal to]2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and [greater than or equal to]2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement. Conclusions In this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences., Author(s): Michael E. Herce 1,2,*, Maganizo B. Chagomerana 1,2, Lauren C. Zalla 3, Nicole B. Carbone 1, Benjamin H. Chi 4, Michael T. Eliya 5, Sam Phiri 2,6, Stephanie M. [...]

Over the past decade, services to prevent mother-to-child transmission (PMTCT) ofhuman immunodeficiency virus (HIV) have expanded rapidly, resulting in reductions in paediatric acquired immunodeficiency syndrome (AIDS) worldwide. (1) However, although [...]

: Introduction: HIV testing male partners of pregnant and postpartum women can lead to improved health outcomes for women, partners and infants. However, in sub‐Saharan Africa, few male partners get HIV tested during their partner's pregnancy in spite of several promising approaches to increase partner testing uptake. We assessed stakeholders’ views and preferences of partner notification, home‐based testing and secondary distribution of self‐test kits to understand whether offering choices for partner HIV testing may increase acceptability. Methods: Interviewers conducted semi‐structured interviews with HIV‐negative (N = 39) and HIV‐positive (N = 41) pregnant/postpartum women, male partners of HIV‐negative (N = 14) and HIV‐positive (N = 14) pregnant/postpartum women, healthcare workers (N = 19) and policymakers (N = 16) in Malawi and Zambia. Interviews covered views of each partner testing approach and preferred approaches; healthcare workers were also asked about perceptions of a choice‐based approach. Interviews were transcribed, translated and analysed to compare perspectives across country and participant types. Results: Most participants within each stakeholder group considered all three partner testing strategies acceptable. Relationship conflict was discussed as a potential adverse consequence for each approach. For partner notification, additional barriers included women losing letters, being fearful to give partners letters, being unable to read and men refusing to come to the clinic. For home‐based testing, additional barriers included lack of privacy or confidentiality and fear of experiencing community‐level HIV stigma. For HIV self‐test kits, additional barriers included lack of counselling, false results and poor linkage to care. Preferred male partner testing options varied. Participants preferred partner notification due to their respect for clinical authority, home‐based testing due to their desire to prioritize convenience and clinical authority, and self‐test kits due to their desire to prioritize confidentiality. Less than half of couples interviewed selected the same preferred male partner testing option as their partner. Most healthcare workers felt the choice‐based approach would be acceptable and feasible, but noted implementation challenges in personnel, resources or space. Conclusions: Most stakeholders considered different approaches to partner HIV testing to be acceptable, but concerns were raised about each. A choice‐based approach may allow women to select their preferred method of partner testing; however, implementation challenges need to be addressed., Abbreviations Introduction Despite advances in HIV prevention of mother‐to‐child transmission (PMTCT) in sub‐Saharan Africa (SSA), pregnant and postpartum women face a high risk of HIV acquisition from infected male partners [...]

Objective To evaluate if a pilot programme to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) was associated with changes in early childhood survival at the population level in rural Zambia. Methods Combination antiretroviral regimens were offered to pregnant and breastfeeding, HIV-infected women, irrespective of immunological status, at four rural health facilities. Twenty-four-month HIV-free survival among children born to HIV- infected mothers was determined before and after PMTCT programme implementation using community surveys. Households were randomly selected and women who had given birth in the previous 24 months were asked to participate. Mothers were tested for HIV antibodies and children born to HIV-infected mothers were tested for viral deoxyribonucleic acid. Multivariable models were used to determine factors associated with child HIV infection or death. Findings In the first survey (2008-2009), 335 of 1778 women (18.8%) tested positive for HIV. In the second (2011), 390 of 2386 (16.3%) tested positive. The 24-month HIV-free survival in HIV-exposed children was 0.66 (95% confidence interval, CI: 0.63- 0.76) in the first survey and 0.89 (95% CI: 0.83-0.94) in the second. Combination antiretroviral regimen use was associated with a lower risk of HIV infection or death in children (adjusted hazard ratio: 0.33,95% CI: 0.15-0.73). Maternal knowledge of HIV status, use of HIV tests and use of combination regimens during pregnancy increased between the surveys. Conclusion The PMTCT programme was associated with an increased HIV-free survival in children born to HIV-infected mothers. Maternal utilization of HIV testing and treatment in the community also increased. Objectit Lvaluer si un programme pilote pour prevenir la transmission mere-enfant (PTME) du virus de l'immunodeficience humaine (VIH) est associe a des changements en matiere de survie du jeune enfant au sein de la population dans les regions rurales de la Zambie. Methodes Des therapies antiretrovirales combinees ont ete proposees a des femmes infectees par le VIH, enceintes et allanantes, independamment de leur statut immunologique, dans quatre centres de sante ruraux. La survie sans VIH a 24 mois chez les enfants nes de meres infectees par leVIH aetedetermineeavantetapres la mise en ceuvredu programme PTME a l'aide d'enquetes communautaires. Les menages ont ete choisis de maniere aleatoire, et il a ete demande aux femmes qul avaient accouche au cours des 24derniers mois, d'y participen On a teste la presence d'anticorps antl-VIH chez les meres et d'acide desoxyribonucleique viral chez les enfants nes de meres infectees par le VIH. Des modeles a variables multiples ont ete utilises pour determiner lesfacteurs associes a l'infection par le VIH ou au deces de l'enfant. Resultats Dansla premiere etude (2008-2009), 335 femmes parmi 1778 (18,8%) ont ete testees positives a l'infection par leVIH. Dans la deuxieme etude (2011), 390 femmes parmi 2386 (16,3%) ont ete testees positives. La survie sans VIH a 24 mois chez les enfants exposes au VIH etait de 0,66 (intervalle de confiance de 95%, IC: 0,63-0,76) dans la premiere etude et de 0,89 (IC de 95%: 0,83-0,94) dans la seconde. La combinalson de la therapie antiretrovirale etait associeea un risque inferieurd'infection par le VIH ou de deces chez les enfants (rapport de risques ajuste: 0,33, IC de 95%: 0,15-0,73). La connaissance du statut VIH des meres, l'utilisation des tests de depistage du VIH et des traitements combines pendant la grossesse ont augmente entre les etudes. Conclusion Le programme PTME etait associe a une augmentation de la survie sans VIH chez les enfants nes de meres infectees par leVIH. L'utilisation par les meres du depistage et du traitement contre leVIH a egalement augmente au sein de la communaute. Objetivo Evaluar si un programa piloto para prevenir la transmision maternoinfantil (PTMI) del virus de la inmunodeficiencia humana (VIH) esta asociado a cambios en la supervivencia en la primera infancia a nivel de poblacion en las zonas rurales de Zambia. Metodos Se ofrecio una combinacion de tratamientos antirretroviraies a mujeres embarazadas y lactantes infectadas por el VIH, independientemente de su estado inmunologico, en cuatro centros de salud rurales. Mediante encuestas en la comunidad se determino una supervivencia sin VIH de veinticuatro meses entre los ninos nacidos de madres infectadas por el VIH antes y despues de la implementacion del programa PTMI. Los hogares se seleccionaron al azar y se pidio que participaran las mujeres que habian dado a luz en los 24 meses anteriores. Las madres se sometieron a una prueba para detectar los anticuerpos contra el VIH y se realizo una prueba del acido desoxirribonucleico viral a los ninos nacidos de madres infectadas con VIH. Se utilizaron modelos multivariables para determinar los factores asociados con la infeccion o muerte por VIH del nino. Resultados En la primera encuesta (2008-2009), 335 de 1778 mujeres (18,8%) dieron positivo en el VIH. En la segunda (2011), dieron positivo 390 de 2386 (16,3%). La supervivencia sin VIH de 24 meses en los ninos expuestos al VIH fue del 0,66 (intervalo de confianza del 95 %, IC: 0,63-0,76) en la primera encuesta y del 0,89 (IC del 95 %: 0,83-0,94) en la segunda. La combinacion de un tratamiento antirretroviral se asocio con un menor riesgo de infeccion por VIH o muerte en los ninos (razon de riesgo ajustada: 0,33,1C del 95 %: 0,15-0,73). El conocimiento de las madres de su estado serologico, el uso de pruebas para el VIH y los tratamientos combinados durante el embarazo aumentaron en el tiempo transcurrido entre las encuestas. Conclusion El programa PTMI estuvo asociado a un aumento de la supervivencia sin VIH en los ninos nacidos de madres infectadas por el VIH. La utilizacion materna de la prueba y el tratamiento del VIH en la comunidad tambien aumento., Introduction In recent years, studies have shown unequivocally that the use of combination antiretroviral regimens, for either treatment or prophylaxis, during the antenatal, intrapartum and breastfeeding periods in women with [...]