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Efforts to prevent mother-to-child transmission of human immunodeficiency virus (HIV) have led to dramatic reductions in pediatric HIV worldwide. New advances in HIV treatment and prevention, focused on pregnant and breastfeeding women living with HIV, have improved maternal health while decreasing vertical and horizontal HIV transmission. In this article, we describe how such interventions-including antiretroviral therapy and HIV pre-exposure prophylaxis-can be incorporated into antepartum and postpartum care in global settings.

Patients stable on antiretroviral therapy (ART) may require transfer between health care facilities to maintain continuous care, yet data on the frequency, predictors, and virologic outcomes of transfers are limited.Data for all viral load (VL) testing at public sector health facilities in the Western Cape Province (2011-2018) were obtained. Participant inclusion criteria were a first VL between 2011 and 2013, age15 years at ART initiation, and1 VL within 5 years of ART initiation, of which ≥1 was at a primary health care facility. Two successive VLs taken at different facilities indicated a transfer. We assessed predictors of transfer using generalized estimating equations with Poisson regression and the association between transfer and subsequent VL1000 copies/mL using generalized mixed effects.Overall 84,814 participants (median age at ART initiation 34 years and 68% female) were followed up for up to 4.5 years after their first VL: 34% (n = 29,056) transferred at least once, and among these, 26% transferred twice and 11% transferred thrice or more. Female sex, age30 years, and first VL1000 copies/mL were independently associated with an increased rate of transfer [adjusted rate ratio 1.24, 95% confidence interval (CI): 1.21 to 1.26; 1.34, 95% CI: 1.31 to 1.36; and 1.42, 95% CI: 1.38 to 1.45, respectively]. Adjusting for age, sex, and disengagement, transfer was associated with an increased relative odds of VL1000 copies/mL (odds ratio 1.35, 95% CI: 1.29 to 1.42).Approximately one-third of participants transferred and virologic outcomes were poor post-transfer. Stable patients who transfer may require additional support to maintain adherence.

Background Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). Methods We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. Results Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22–30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15–34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16–43%) infants in the POC group vs 7 (19%; 6–32%) in the SOC group (RR: 1.56; .7–3.50). Conclusions POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. Clinical Trials Registration This trial is registered at https://clinicaltrials.gov (NCT02682810).

Pre-exposure prophylaxis (PrEP) is a promising tool for HIV prevention during pregnancy. With increasing rollout in antenatal settings, counselling strategies to help pregnant women make appropriate decisions about PrEP use are needed. Understanding women's motivations and concerns for PrEP use-and how these inform their decision making and feelings about the decision to start PrEP-are critical to inform these strategies.We conducted a convergent mixed-methods study from June 2020 to June 2021 in the context of a PrEP adherence support trial among HIV-negative pregnant women in Lilongwe, Malawi. Two hundred women completed a survey reporting their motivations and concerns about PrEP use, and their feelings about the decision to start PrEP (Decisional Regret Scale). Thirty women completed in-depth interviews to better understand the decision-making process, including motivations and concerns weighed in women's decision to use PrEP. Analyses comprised descriptive and bivariate statistics, thematic qualitative analysis, and integration of quantitative and qualitative results.Women initiating PrEP during pregnancy were highly motivated to obtain HIV protection for themselves and their unborn child, often due to perceived HIV risk connoted by a recent sexually transmitted infection and/or concerns about partner non-monogamy. These motivations prevailed despite some concerns about safety and side effects, anticipated stigmatization, and concerns about adherence burden and pill attributes. Many women had informed their partner of their decision to use PrEP yet few felt their decision was contingent upon partner approval. Most women felt positively about the decision to start PrEP (mean decisional regret = 1.2 out of 5), but those with a greater number of concerns reported greater decisional regret (B = 0.036; p = 0.005). Furthermore, women who were specifically concerned about partner disclosure, who disliked pills or who had no perceived HIV risk reported greater decisional regret.Pregnant women were strongly motivated by the promise of HIV protection offered by PrEP and accepted it despite diverse concerns. A shared decision-making approach that centres pregnant women and offers partner involvement may help identify and address initial concerns about PrEP use and support prevention-effective use of PrEP during this important period.

There is increasing focus in HIV prevention and treatment on couples-based approaches. No systematic review has synthesized prospective behavioral couples-based HIV trials targeting prevention of mother-to-child transmission (PMTCT) outcomes in low- and middle-income countries (LMICs). We systematically reviewed published abstracts and articles reporting prospective comparative evaluations of behavioral couples-based HIV interventions delivered during pregnancy to both members of a self-identified heterosexual couple in LMICs following PRISMA. Citations, abstracts, and full texts were double screened for eligibility. References meeting eligibility criteria underwent double data abstraction, quality appraisal, and qualitative synthesis. We identified 295 unique publications. Of these, 5 randomized trials were deemed eligible and synthesized. Studies were conducted in 3 different African countries using three overarching intervention approaches: home-based; group workshops; and faith-based. Studies included various PMTCT outcome measures. We found evidence that behavioral couples-based approaches around the time of pregnancy can positively affect HIV testing among pregnant women and their male partners, infant HIV prophylaxis use, and HIV-free infant survival. The effects on other PMTCT outcomes were not well supported. There was a low to moderate risk of bias among the included studies. Few couples-based PMTCT interventions have been tested in LMICs. Of the interventions we located, workshops/group education and home-based couple counseling and testing were most commonly used to promote PMTCT. Research is needed on the role of relationship dynamics within such interventions and whether couples-based approaches during pregnancy can extend to health outcomes across the PMTCT continuum of care.

This study sought to explore and contextualise the man's role in antenatal services, and the barriers and strategies for engaging men in prevention of mother-to-child HIV transmission (PMTCT). We conducted 143 interviews with pregnant and breastfeeding women, male partners, health workers and policy makers in Malawi and Zambia. We employed thematic and critical discourse analysis using the hegemonic masculinity perspective. We found that men's roles in PMTCT reflected hegemonic masculinities. As breadwinners, men supported their partners with material and financial resources. As decision makers, men were involved in decision making on the health of their partners. As social protectors, men supported their partners in accessing and adhering to antenatal care, HIV treatment and care. Barriers and challenges to male involvement in antenatal care were often the result of conflict between the clinic operating hours and men's working hours, the perception of antenatal care services as female spaces, and men's fear of HIV testing. Proposed strategies to increase male engagement in PMTCT included sensitising men about HIV and pregnancy; engaging leaders and employers, providing services outside working hours, and providing incentives. We conclude that men's role and participation in PMTCT services are an extension and adaptation of hegemonic masculinities.

IntroductionPregnant 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.DiscussionPregnancy 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.ConclusionsPregnancy 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.

Background Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW). Methods Directly observed PrEP was administered for 12 weeks in a pregnancy (14–24 weeks’ gestation, n = 20) and postpartum (6–12 weeks postpartum, n = 20) group of AGYW aged 16–24 years in sub-Saharan Africa. Weekly DBS TFV-DP was measured by validated liquid chromatography–tandem mass spectrometry assay. Week 12 TFV-DP distributions were compared between groups with Wilcoxon test. Population pharmacokinetic models were fit to estimate steady-state concentrations and create benchmarks for adherence categories. Baseline correlates of TFV-DP were evaluated. Results Median age was 20 (IQR, 19–22) years. Of 3360 doses, 3352 (>99%) were directly observed. TFV-DP median (IQR) half-life was 10 (7–12) days in pregnancy and 17 (14–21) days postpartum, with steady state achieved by 5 and 8 weeks, respectively. Observed median (IQR) steady-state TFV-DP was 965 fmol/punch (691–1166) in pregnancy versus 1406 fmol/punch (1053–1859) postpartum (P = .006). Modeled median steady-state TFV-DP was 881 fmol/punch (667–1105) in pregnancy versus 1438 fmol/punch (1178–1919) postpartum. In pooled analysis, baseline creatinine clearance was associated with observed TFV-DP concentrations. Conclusions TFV-DP in African AGYW was approximately one-third lower in pregnancy than postpartum. These Population-specific benchmarks can be used to guide PrEP adherence support in pregnant/postpartum African women. Clinical Trials Registration NCT03386578, Concentrations of tenofovir diphosphate in dried blood spots were approximately one-third lower during pregnancy than postpartum after 12 weeks of directly observed dosing among African adolescent girls and young women on daily pre-exposure prophylaxis. We recommend population-specific benchmarks for adherence support.

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.

Background Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. Methods We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Results Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation. Conclusion The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence.

Objective To evaluate the association between HIV antiretroviral therapy (ART) and preterm birth (PTB), when defined by gold standard antenatal ultrasound versus newborn exam. Design A secondary analysis of the PROMISE 1077BF/1077FF randomized controlled trial, which compared antiretroviral strategies to reduce perinatal HIV transmission and improve maternal health. The trial used newborn exam (i.e. New Ballard Score, NBS) to assess gestational age. This analysis included liveborn singleton pregnancies with both newborn exam and ultrasound data. The primary exposure was the trial's antiretroviral strategies: zidovudine with intrapartum nevirapine ('ZDV alone'); zidovudine/lamivudine/lopinavir-ritonavir ('ZDV-based ART'); or tenofovir/emtricitabine/lopinavir-ritonavir ('TDF-based ART'). The primary outcome was PTB less than 37 and less than 34 weeks based on the gold standard of ultrasound dating. We evaluated the association between antiretroviral strategy and PTB. We fit multivariable logistic regression models, adjusting for maternal characteristics, obstetric history, and HIV disease severity. Results Among 720 assessed pregnant women, PTB less than 37 weeks was 15.4% by NBS and 18.3% by ultrasound. The NBS was specific but not sensitive for PTB less than 37 weeks (92.0% and 48.5%). Women receiving ZDV-based and TDF-based ART had significantly higher odds of PTB less than 37 by ultrasound compared with ZDV alone (adjusted odds ratios: 1.68; 95% confidence interval 1.10-2.57, and 2.71; 95% confidence interval 1.39-5.29), as well as for PTB less than 34 weeks. These results held for ultrasounds performed less than 24 weeks, and were generally consistent with prior analyses from the PROMISE trial using the NBS. Conclusion Women starting HIV ART in pregnancy remained at higher risk of PTB when determined by ultrasound, consistent with prior data using newborn exam. However, newborn exam misclassified cases of PTB compared with gold standard ultrasound.

Summary Background Testing men for HIV during their partner's pregnancy can guide couples-based HIV prevention and treatment, but testing rates remain low. We investigated a combination approach, using evidence-based strategies, to increase HIV testing in male partners of HIV-positive and HIV-negative pregnant women. Methods We did two parallel, unmasked randomised trials, enrolling pregnant women who had an HIV-positive test result documented in their antenatal record (trial 1) and women who had an HIV-negative test result documented in their antenatal record (trial 2) from an antenatal setting in Lusaka, Zambia. Women in both trials were randomly assigned (1:1) to the intervention or control groups using permuted block randomisation. The control groups received partner notification services only, including an adapted version for women who were HIV-negative; the intervention groups additionally received targeted education on the use of oral HIV self-test kits for their partners, along with up to five oral HIV self-test kits. At the 30 day follow-up we collected information from pregnant women about their primary male partner's HIV testing in the previous 30 days at health-care facilities, at home, or at any other facility. Our primary outcome was reported male partner testing at a health facility within 30 days following randomisation using a complete-case approach. Women also reported male partner HIV testing of any kind (including self-testing at home) that occurred within 30 days. Randomisation groups were compared via probability difference with a corresponding Wald-based 95% CI. The trial is registered at ClinicalTrials.gov ( NCT04124536 ) and all enrolment and follow-up has been completed. Findings From Oct 28, 2019, to May 26, 2020, 116 women who were HIV-positive (trial 1) and 210 women who were HIV-negative (trial 2) were enrolled and randomly assigned to study groups. Retention at 30 days was 100 (86%) in trial 1 and 200 (95%) in trial 2. Women in the intervention group were less likely to report facility-based male partner HIV testing in trial 1 (3 [6%] of 47 vs 15 [28%] of 53, estimated probability difference –21·9% [95% CI –35·9 to –7·9%]) and trial 2 (3 [3%] of 102 vs 33 [34%] of 98, estimated probability difference –30·7% [95% CI –40·6 to –20·8]). However, reported male partner HIV testing of any kind was higher in the intervention group than in the control group in trial 1 (36 [77%] of 47 vs 19 [36%] of 53, estimated probability difference 40·7% [95% CI 23·0 to 58·4%]) and trial 2 (80 [78%] of 102 vs 54 [55%] of 98, estimated probability difference 23·3% [95% CI 10·7 to 36·0%]) due to increased use of HIV self-testing. Overall, 14 male partners tested HIV-positive. Across the two trials, three cases of intimate partner violence were reported (two in the control groups and one in the intervention groups). Interpretation Our combination approach increased overall HIV testing in male partners of pregnant women but reduced the proportion of men who sought follow-up facility-based testing. This combination approach might reduce linkages to health care, including for HIV prevention, and should be considered in the design of comprehensive HIV programmes. Funding National Institutes of Health.

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 wellbeing of pregnant people and their children.

Background: In an era of global health security challenges such as the COVID-19 pandemic, there is greater need for strong leadership. Over the past decades, significant investments have been made in global health leadership development programs by governments and philanthropic organizations to address this need. Evaluating the societal impact of these programs remains challenging, despite consensus on the importance of public health leadership. Objective: This article identifies the gaps and highlights the critical role of monitoring and evaluation approaches in assessing the impact of global health leadership programs. Importantly, we also propose the theory of change (TOC) as a common framework and identify a set of tools and indicators that leadership programs can adapt and use. Methods:We carried out an informal review of major global health leadership programs, including a literature review on leadership program evaluation approaches. Current practices in assessing the short- to long-term outcomes of leadership training programs were explored and synthesized. We also examined use of program theory frameworks, such as theory of change to guide the evaluation strategy. We find the TOC approach can be enhanced by integrating evaluation-specific frameworks and establishing broad stakeholder buy-in. We highlight measurement challenges, proposed outcome indicators and evaluation methodologies, and outline the future direction for such efforts. Findings: Most evaluation of current leadership programs is focused on short-term individual-level outcomes, while reports on long-term societal impact were limited. Reciprocal impacts on and benefits for the “host” organizations were not included in evaluation metrics. Most programs had program logic or result chains, but with no well-articulated program theories. Conclusion: Key stakeholders involved in leadership training programs benefit from the evidence of rigorous program evaluations to inform decisions that address barriers in fostering global health leadership and improving population health outcomes. Insight into reciprocal change in host organizations is important. Evaluation of global health leadership training must go beyond the individual trainee and encompass organizational and community-level impacts. Documentation of long-lasting organizational and societal impacts is essential for donors to appreciate the return on their investment. Key Takeaways Evaluation plays an important role in understanding how leadership development takes place and how it contributes to improving public health outcomes. Making the case for investments in leadership development programs requires robust evidence from monitoring and evaluation strategies that link investments beyond the individual-level to longer-term societal impacts. The first critical step towards a strategy for success is for leadership programs to clearly build, articulate, share, and use their program theories or theories of change. Theories of change help identify the pathways (and potential tensions) through which leadership development programs effect change at the individual, organizational and community levels. Evaluation methods that examine outcomes of leadership programs should be multi-method, multi-level, and where possible include counterfactual outcomes. Allocation of funds to evaluate on-going and long-lasting societal impact of leadership programs should be a routine practice.

IntroductionTo realise the expected gains from prevention of mother-to-child HIV transmission initiatives, adherence to preventative and therapeutic antiretroviral regimens is critical and interventions deployable in busy programmatic settings with a high HIV burden are needed. Based on formative research, we developed an approach that integrates patient-centred counselling and engagement of an adherence supporter for pregnant and breastfeeding women initiating HIV treatment (ie, antiretroviral therapy (ART)) or biomedical HIV prevention (ie, pre-exposure prophylaxis (PrEP)).MethodsTonse Pamodzi 2 is a pilot study designed to provide acceptability, fidelity and clinical outcomes data on a set of behavioural interventions for adherence support. The study comprises two parallel randomised trials, enrolling HIV-positive pregnant women initiating ART (Trial 1, n=100) and HIV-negative pregnant women with risk of HIV acquisition and willing to initiate PrEP (Trial 2, n=200). Within each trial, participants are randomised 1:1 to either the intervention or control group. The Tonse Pamodzi adherence intervention comprises patient-centred counselling (adapted Integrated Next Step Counseling(iNSC)) and external adherence support tailored to the clinical context (ie, for ART or PrEP). Participants randomly assigned to the control group receive standard counselling based on local HIV guidelines. Participants are followed for 6 months. To assess intervention acceptability, we will employ a mixed method approach to describe participant engagement, satisfaction, and discussion content. We will audit and score recorded counselling sessions to evaluate the implementation fidelity of iNSC sessions. We will also assess clinical outcomes at 3 and 6 months for both Trial 1 (retention in care and viral suppression of HIV) and Trial 2 (retention in care, and plasma and intracellular tenofovir drug concentrations).Ethics and disseminationThe study protocol was approved by the Malawi National Health Science Research Committee (19/05/2334) and the University of North Carolina at Chapel Hill Institutional Review Board (19-1060).Trial registration numberNCT04330989.

In the multicountry PROMISE 1077BF/1077FF trial, the risk of low birth weight (LBW;2500 g) and preterm delivery (PTD;37 weeks) was significantly higher among women initiating a protease inhibitor-based antiretroviral treatment (ART) regimen than those receiving ZDV alone. Among those assigned to a protease inhibitor regimen, tenofovir/emtricitabine was associated with the more severe outcomes of very LBW (1500 g) and very PTD (34 weeks) compared with zidovudine/lamivudine.We used multivariate logistic regression to further explore these treatment findings, taking into account demographic baseline clinical and postentry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion.Among 3333 women delivering at least 1 live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least 1 previous PTD. Seventeen percent of newborns were LBW, 1% were very LBW, 17% had PTD, and 3% had very PTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included the following: country, gestational age at entry, maternal age, maternal body mass index, previous PTD, history of alcohol use, baseline HIV viral titer, multiple gestation, and several obstetric risk factors.ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical, and obstetrical risk factors, which were also associated with these outcomes.

Introduction Interpersonal support can promote positive outcomes among people living with HIV. In order to develop an acceptable psychoeducational couples-based intervention aimed at strengthening the relationship context and improving HIV outcomes before and after pregnancy, we conducted qualitative interviews with pregnant women living with HIV and their male partners. Methods We interviewed a convenience clinic-based sample of pregnant women living with HIV (n = 30) and male partners (n = 18) in Lusaka, Zambia. Interviews included pile sorting relationship topics in order of perceived priority. Interviews also focused on family health concerns. Interviews were audio-recorded, translated, transcribed, and thematically analyzed. Pile sorting data was analyzed using descriptive statistics. Results All female participants were living with HIV; 61% of the male partners interviewed were additionally living with HIV. The most prioritized relationship topic among both genders was communication between couples. Honesty and respect were important relationship topics but prioritized differently based on gender. Female participants considered emotional and instrumental support from male partners critical for their physical and mental health; men did not prioritize support. Intimate partner violence was discussed often by both genders. Family health priorities included good nutrition during pregnancy, preventing infant HIV infection, safe infant feeding, sexual health, and men's alcohol use. Conclusions A major contribution of this study is a better understanding of the dyad-level factors pregnant women living with HIV and their male partners perceive to be the most important for a healthy, well-functioning relationship. This study additionally identified gaps in antenatal health education and the specific family health issues most prioritized by pregnant women living with HIV and their male partners. The findings of this study will inform the development of an acceptable couples-based intervention with greater likelihood of efficacy in strengthening the relationship context and promoting family health during and after pregnancies that are affected by HIV.

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi (“all of us together”), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT.

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

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.

As one of the six consortia funded through the NIH Fogarty International Center, the University of North Carolina at Chapel Hill, Johns Hopkins University, Morehouse School of Medicine, and Tulane University (UJMT) Fogarty Global Health Fellows Program provides postdoctoral trainees and doctoral students support and training for yearlong research attachments at selected low- and middle-income countries. To understand the current impact of this global health research training opportunity, the UJMT consortium conducted a crowdsourcing contest to gather creative messages to promote and improve the impact of the program in partnership with Social Entrepreneurship to Spur Health. Between January and March 2019, the contest received a total of 47 submissions from 14 countries; 44 were found eligible. After judging, 19 (41.2%) submissions received a mean score of 7 or higher. We examined both textual and descriptive submissions for emergent themes and identified a range of facilitators who can be used to further improve the training programs; examples include exceptional mentorship, acquisition of research skills, career development, personal development, and multisite training opportunities. In conclusion, the crowdsourcing mentorship contest demonstrated the feasibility and acceptability of leveraging existing research networks for community engagement and how useful information can be effectively collected to highlight the effectiveness of a program and expand the reach.

Pregnancy is a period of high HIV acquisition risk for African women, and pregnant women who become acutely infected with HIV account for up to one-third of vertical HIV transmissions. To protect women and eliminate vertical transmission, the World Health Organization recommends offering oral tenofovir-based pre-exposure prophylaxis (PrEP) to HIV-negative pregnant and postpartum women with substantial HIV acquisition risk. PrEP implementation for pregnant and postpartum women lags behind other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and postpartum, including integration of provider training, clinical delivery, and monitoring PrEP exposure and outcomes within existing maternal health systems, yet few implementation data are available to generate evidence in this context. In this Viewpoint, we examine current PrEP delivery among pregnant and postpartum African women, identify gaps in evidence according to the RE-AIM framework, and offer recommendations to guide the implementation science research agenda to optimize PrEP for these populations.

Objectives A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence. Design Systematic review and meta-analysis. Methods We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression. Results Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval: 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval: 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval: 0.7--6.5). Conclusion Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women.

Fertility intentions are thought to be dynamic among women of reproductive age, yet few studies have assessed fertility intentions over time among women with HIV. We examine temporal patterns of fertility intentions in women with HIV to assess the extent to which fertility intentions - and the corresponding need for safer conception and judicious antiretroviral therapy (ART) regimen selection - vary over time. 850 non-pregnant HIV-positive women aged 18–35 on or being initiated onto ART in Johannesburg, South Africa were enrolled into a prospective cohort study in 2009–2010. Fertility intentions were assessed at enrolment and at 30-day intervals via a short interviewer-administered questionnaire. We used group-based trajectory modelling to identify longitudinal patterns of fertility intentions over 12 months. We identified four patterns of fertility intentions, which we labelled “consistently low” (representing ~60% of the population), “low and increasing” (~23%), “high and increasing” (~12%), and “high and decreasing” (~5%). Our finding that more than a third of women (those following “increasing” or “decreasing” patterns) exhibited changes in their fertility intentions over a 12-month period suggests that a single family-planning assessment at one time point is insufficient to fully identify and meet the reproductive needs of women with HIV. As HIV testing and treatment evolve in South Africa, routine screening for fertility intentions can better direct care delivery, offering important opportunities to optimize HIV treatment, prevention and maternal and child health.

Author(s): Joseph Davey, Dvora L; Pintye, Jillian; Baeten, Jared M; Aldrovandi, Grace; Baggaley, Rachel; Bekker, Linda-Gail; Celum, Connie; Chi, Benjamin H; Coates, Thomas J; Haberer, Jessica E; Heffron, Renee; Kinuthia, John; Matthews, Lynn T; McIntyre, James; Moodley, Dhayendre; Mofenson, Lynne M; Mugo, Nelly; Myer, Landon; Mujugira, Andrew; Shoptaw, Steven; Stranix-Chibanda, Lynda; John-Stewart, Grace; PrEP in Pregnancy Working Group | Abstract: 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 g6200 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.

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 ≤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%) ≥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 ≥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., Michael Herce and co-workers study potential improvements in linkage to care for prevention of mother to child transmission of HIV in Malawi., Author summary Why was this study done? Attrition from the prevention of mother-to-child transmission of HIV (PMTCT) continuum threatens health gains for pregnant and breastfeeding women (PBFW) living with HIV and their infants. To improve PMTCT services in Africa, 3 community-facility linkage (CFL) models—Mentor Mothers, Community Health Workers (CHWs), and Expert Clients/Patients—have been widely implemented. Available evidence suggests that these CFL models may improve the health of PBFW living with HIV and their infants. Despite the promise of CFL models, however, no studies from the current “treat all” era have attempted to examine which of these models works best in “real world” PMTCT programs for ensuring maternal HIV care retention and viral suppression and infant HIV-free survival. What did the researchers do and find? We conducted a descriptive study in Malawi by sampling busy health facilities in 5 districts and, at selected facilities, reviewing medical records for all newly HIV-diagnosed PBFW and their HIV-exposed infants. We then administered a survey to a randomly selected subset of these mother–infant pairs to assess CFL model exposure and HIV outcomes. We found that compared to women supported by the most common CFL model, Expert Clients, women supported by CHWs were 13% more likely to start antiretroviral therapy (ART) soon after their HIV diagnosis. Over the 2 years following HIV diagnosis, PBFW living with HIV who received CHW model support spent 14% more time retained on ART and virally suppressed than women in the Expert Client model. Infants receiving Mentor Mother model support were 24% more likely to receive HIV testing by age 6 months than infants supported by Expert Clients. The 12-month infant risk of experiencing a positive HIV test result, loss to follow-up, or death did not vary significantly by CFL model. What do these findings mean? CFL models had widespread coverage in the national PMTCT/ART program in our selected sites in Malawi, reaching most mother–infant pairs. Important differences were noted in maternal and infant HIV outcomes by CFL model. Favorable HIV outcomes were seen in women supported by the CHW model, and higher infant EID testing uptake was observed in infants supported by Mentor Mothers. Although caution should be exercised when applying our findings to other settings, we found that CFL models may have different impacts on maternal and infant HIV outcomes at different steps along the PMTCT continuum in Malawi. Future research should identify the key features of CFL models that drive these outcome differences to better inform PMTCT programming in Malawi.

Background: Despite the burden of HIV being highest in sub-Saharan Africa (SSA), research expertise and capacity to address scientific questions regarding complications of HIV and ART, especially chronic non-communicable conditions, is limited in the region. The comorbidities prevalent in persons with HIV are mediated through diverse mechanisms, many of which can be context or region-specific and are yet to be elucidated. The phenotype, risk factors, and effective interventions for these conditions may differ between populations and settings, and therefore there is an urgent need for research to help understand these processes and how to best address them in SSA. Here, we report the research capacity building activities in SSA conducted by the University of Zambia (UNZA)-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research (UVP), drawing lessons and challenges for a wide global health audience. Methods: We reviewed program data and conducted interviews with program leaders and participants to understand and document the progress and outcomes of the partnership. We report the program’s early achievements, highlighting drivers and challenges. Results: Between 2015 and 2019, UVP made substantial progress on its goals of training new UNZA PhD scientists to investigate complex nutritional and metabolic factors related to long-term HIV complications and comorbidities. The program has supported 11 UNZA PhD students with dual UNZA-Vanderbilt mentorship; three have graduated, and other candidates are progressing in their PhD studies. The project also supported institutional capacity through UNZA faculty participation in Vanderbilt grant writing workshops, with strong success in obtaining grants among those who participated. UVP also supported development of greater structure to UNZA’s PhD program and a mentorship curriculum, both now adopted by UNZA. The major drivers for success included UVP’s alignment of goals between UNZA and Vanderbilt, and local institutional ownership. The longstanding history of collaborations between the two institutions contributed substantially to alignment and mutual support of UVP’s goals. Several challenges were noted, including limits on direct research funding for students and a relatively small pool of funded investigators at UNZA. Conclusions: Despite some challenges, UVP has achieved positive outcomes over its first four years. Longstanding partnerships and local institutional ownership were the main drivers. We expect the challenges to mitigated as the project continues and produces more UNZA researchers and teams and more funded projects, collectively building the local research community. With continued resources and clear focus, we expect that UNZA’s investigators and partners will attract research funding and generate high-impact research outputs across a broad range of studies in HIV as well as newer threats from non-communicable conditions experienced by long-term survivors of HIV and by the general population.

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.

Poor HIV care retention impedes optimal treatment outcomes in persons living with HIV. Women trying to become pregnant may be motivated by periconception horizontal and vertical transmission concerns and thus more likely to attend HIV care visits than women not trying to conceive. We estimated the effect of fertility intentions on HIV care attendance over 12 months among non-pregnant, HIV-positive women aged 18–35 years who were on or initiating antiretroviral therapy in Johannesburg, South Africa. The percentage of women attending an HIV care visit decreased from 93.4% in the first quarter to 82.8% in the fourth quarter. Fertility intentions were not strongly associated with care attendance in this cohort of reproductive-aged women; however, attendance declined over time irrespective of childbearing plans. These findings suggest a need for reinforced efforts to support care engagement and risk reduction, including safer conception practices for women wishing to conceive.

Background HIV viral load (VL) and resistance testing are limited in sub-Saharan Africa, so individuals may have prolonged time on failing first-line antiretroviral therapy (ART). Our objective was to describe the evolution of drug resistance mutations among adults failing first-line ART in Zambia. Methods We analysed data from a trial of VL monitoring in Lusaka, Zambia. From 2006 to 2011, 12 randomized sites provided either routine VL monitoring (intervention) or discretionary (control) after ART initiation. Samples were collected prospectively following the same schedule in each arm but analysed retrospectively in the control group. For those with virological failure (VF; >400 copies/ml), HIV genotyping was performed retrospectively on baseline (BL) and on all subsequent specimens until censored due to study completion, withdrawal or death. Results Of 1,973 enrollees, 165 (8.4%) developed VF. 464 genotype results were available including 132 (80%) at BL, 116 (70%) at VF and 125 (76%) had at least one result between VF and censoring. Major nucleoside reverse transcriptase inhibitor (NRTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations increased from 26% (BL) to 82% (VF) to 89% at last genotype (LG). M184 mutations increased from 2% to 59% to 71%; K65R from 2% to 11% to 13%; 2 or more thymidine analogue mutations from 1% to 3% to 12%. Among those on a failing tenofovir disoproxil fumarate (TDF)-based regimen, TDF resistance increased from 42% to 58%. Conclusions We found substantial resistance to NRTIs and NNRTIs at VF with incremental increases after VF while still on a failing first-line ART; this resistance may compromise attainment of the UNAIDS 90-90-90 goals.

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. Fil: Chi, Benjamin H.. University of North Carolina; Estados Unidos Fil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Blas, Magaly M.. Universidad Peruana Cayetano Heredia; Perú Fil: Chuang, Alice. University of North Carolina; Estados Unidos Fil: Wilson, Michael D.. University Of Ghana; Ghana Fil: Chibwesha, Carla J.. University of North Carolina; Estados Unidos Fil: Farquhar, Carey. University of Washington; Estados Unidos Fil: Cohen, Craig R.. University of California; Estados Unidos Fil: Raj, Tony. St. John’s Research Institut; India

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4+ T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery. Methods: Women with pre-ART CD4+ cell counts ≥350 cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat. Findings: 1611 women were enrolled (June 2011–October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4+ count 728 cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p = 0.37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p = 0.01). The arms did not differ with respect to the rate of grade 2, 3, or 4 safety events (p = 0.61). Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4+ cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

High HIV incidence rates have been observed among pregnant and breastfeeding women in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) can effectively reduce HIV acquisition in women during these periods; however, understanding of its acceptability and feasibility in antenatal and postpartum populations remains limited. To address this gap, we conducted in-depth interviews with 90 study participants in Malawi and Zambia: 39 HIV-negative pregnant/breastfeeding women, 14 male partners, 19 healthcare workers, and 18 policymakers. Inductive and deductive approaches were used to identify themes related to PrEP. As a public health intervention, PrEP was not well-known among patients and healthcare workers; however, when it was described to participants, most expressed positive views. Concerns about safety and adherence were raised, highlighting two critical areas for community outreach. The feasibility of introducing PrEP into antenatal services was also a concern, especially if introduced within already strained health systems. Support for PrEP varied among policymakers in Malawi and Zambia, reflecting the ongoing policy discussions in their respective countries. Implementing PrEP during the pregnancy and breastfeeding periods will require addressing barriers at the individual, facility, and policy levels. Multi- level approaches should be considered in the design of new PrEP programs for antenatal and postpartum populations.

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.

Objective We evaluated residual incontinence, depression, and quality of life among Malawian women who had undergone vesicovaginal fistula (VVF) repair 12 or more months previously. Design Prospective cohort study. Setting Fistula Care Centre in Lilongwe, Malawi. Population Women who had undergone VVF repair in Lilongwe, Malawi at least 12 months prior to enrolment. Methods Self-report of urinary leakage was used to evaluate for residual urinary incontinence; depression was evaluated with the Patient Health Questionnaire-9; quality of life was evaluated with the King's Health Questionnaire. Main outcome measures Prevalence and predictors of residual incontinence, quality of life scores, and prevalence of depression and suicidal ideation. Results Fifty-six women (19.3%) reported residual urinary incontinence. In multivariable analyses, predictors of residual urinary incontinence included: pre-operative Goh type 3 [adjusted risk ratio (aRR) 2.82; 95% confidence interval (CI) 1.61-5.27) or Goh type 4 1.08-2.78), positive postoperative cough stress test (aRR = 2.42; 95% CI 1.24-4.71) and the positive 1-hour postoperative pad test (aRR = 2.20; 95% CI 1.08-4.48). Women with Goh types 3 and 4 VVF reported lower quality of life scores. Depressive symptoms were reported in 3.5% of women; all reported residual urinary incontinence. Conclusions While the majority of women reported improved outcomes in the years following surgical VVF repair, those with residual urinary incontinence had a poorer quality of life. Services are needed to identify and treat this at-risk group. Tweetable abstract Nearly one in five women reported residual urinary incontinence at follow up, 12 or months after vesicovaginal fistula repair.

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.

To estimate the association between duration of combination antiretroviral therapy (cART) during pregnancy and low infant birthweight (LBW), among women ≥37 weeks of gestation.We conducted a retrospective cohort study of HIV-infected women who met eligibility criteria based on CD4 count ≤350 but had not started cART at entry into antenatal care. Our cohort was restricted to births that occurred ≥37 weeks of gestation.We used Poisson models with robust variance estimators to estimate risk ratios (RRs) and 95% confidence intervals (CIs).Of 50,765 HIV-infected women with antenatal visits between January 2009 and September 2013, 4474 women met the inclusion criteria. LBW occurred in 302 pregnancies (7%). Nearly two-thirds of women (62%) eligible to initiate cART never started treatment. Overall, 14% were on cART for ≤8 weeks, 22% for 9-20 weeks, and 2% for 21-36 weeks. There was no evidence of an increased risk of LBW for women receiving cART for ≤8 weeks (RR = 1.22; 95% CI: 0.77 to 1.91), 9-20 weeks (RR = 1.23; 95% CI: 0.82 to 1.83), or 21-36 weeks (RR = 0.87; 95% CI: 0.22 to 3.46), compared with women who never initiated treatment. These findings were consistent across several sensitivity analyses.Longer duration of cART was not associated with poor fetal growth among term pregnancies in our cohort. However, the relationship between cART and adverse pregnancy outcomes remains complicated. Continued work is required to investigate causality. An understanding cART's impact on adverse pregnancy outcomes is essential as cART becomes the cornerstone of preventing mother-to-child transmission programs globally.

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

Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons.To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples.Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for HBV genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL.Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98logIU/ml (interquartile range, 2.04-5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59logIU/ml lower than plasma with 95% limits of agreement of -2.40 to -0.83log IU/ml. At a plasma VL ≥2,000IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5-6.6). At plasma VL ≥20,000IU/ml this probability reduced to 0.2% (95% CI: 0.03-1.7).In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing and care in SSA settings.

Objective To determine the quality of contraceptive services in family planning clinics in Lusaka, Zambia, using a standardized approach. Study design We utilized the Quick Investigation of Quality, a cross-sectional survey tool consisting of a facility assessment, client–provider observation and client exit interview, in public-sector family planning clinics. Data were collected on availability of seven contraceptive methods, information given to clients, interpersonal relations between providers and clients, providers' technical competence and mechanisms for continuity and follow-up. Results Data were collected from five client–provider observations and client exit interviews in each of six public-sector family planning clinics. All clinics had at least two contraceptive methods continuously available for the preceding 6 months. Most providers asked clients about concerns with their contraceptive method (80%) and told clients when to return to the clinic (87%). Most clients reported that the provider advised what to do if a problem develops (93%), described possible side effects (89%), explained how to use the method effectively (85%) and told them when to come for follow-up (83%). Clients were satisfied with services received (93%). Conclusion(s) This application of the Quick Investigation of Quality showed that the participating family planning clinics in Lusaka, Zambia, were prepared to offer high-quality services with the available commodities and that clients were satisfied with the received services. Despite the subjective client satisfaction, quality improvement efforts are needed to increase contraceptive availability. Implications Although clients perceived the quality of care received to be high, family planning service quality could be improved to continuously offer the full spectrum of contraceptive options. The Quick Investigation of Quality was easily implemented in Lusaka, Zambia, and this simple approach could be utilized in a variety of settings as a modality for quality improvement.

Introduction. Although increasing access to family planning has been an important part of the global development agenda, millions of women continue to face unmet need for contraception.Materials and Methods. We analyzed data from a repeated cross-sectional community survey conducted in Lusaka, Zambia, over an eight-year period. We described prevalence of modern contraceptive use, including long-acting reversible contraception (LARC), among female heads of household aged 16–50 years. We also identified predictors of LARC versus short-term contraceptive use among women using modern methods.Results and Discussion. Twelve survey rounds were completed between November 2004 and September 2011. Among 29,476 eligible respondents, 17,605 (60%) reported using modern contraception. Oral contraceptive pills remained the most popular method over time, but use of LARC increased significantly, from less than 1% in 2004 to 9% by 2011 (p<0.001). Younger women (OR: 0.46, 95% CI: 0.34, 0.61) and women with lower levels of education (OR: 0.70, 95% CI: 0.56, 0.89) were less likely to report LARC use compared to women using short-term modern methods.Conclusions. Population-based assessments of contraceptive use over time can guide programs and policies. To achieve reproductive health equity and reduce unmet contraceptive need, future efforts to increase LARC use should focus on young women and those with less education.

BACKGROUND The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS We analyzed data from 173,245 patients (61% female, 8% children aged 2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus

Women's empowerment is associated with engagement in some areas of healthcare, but its role in prevention of mother-to-child HIV transmission (PMTCT) services has not been previously considered. In this secondary analysis, we investigated the association of women's decision-making and uptake of health services for PMTCT. Using data from population-based household surveys, we included women who reported delivery in the 2-year period prior to the survey and were HIV-infected. We measured a woman's self-reported role in decision-making in her own healthcare, making of large purchases, schooling of children, and healthcare for children. For each domain, respondents were categorized as having an "active" or "no active" role. We investigated associations between decision-making and specific steps along the PMTCT cascade: uptake of maternal antiretroviral drugs, uptake of infant HIV prophylaxis, and infant HIV testing. We calculated unadjusted and adjusted odds ratios via logistic regression. From March to December 2011, 344 HIV-infected mothers were surveyed and 276 completed the relevant survey questions. Of these, 190 (69%) took antiretroviral drugs during pregnancy; 175 (64%) of their HIV-exposed infants received antiretroviral prophylaxis; and 160 (58%) had their infant tested for HIV. There was no association between decision-making and maternal or infant antiretroviral drug use. We observed a significant association between decision-making and infant HIV testing in univariate analyses (OR 1.56-1.85; p 0.05); however, odds ratios for the decision-making indicators were no longer statistically significant predictors of infant HIV testing in multivariate analyses. In conclusion, women who reported an active role in decision-making trended toward a higher likelihood of uptake of infant testing in the PMTCT cascade. Larger studies are needed to evaluate the impact of empowerment initiatives on the PMTCT service utilization overall and infant testing in particular.

In response to the HIV/AIDS pandemic in sub-Saharan Africa the African networks of IeDEA (International epidemiologic databases to Evaluate AIDS) aim to inform the scale-up of ART in the region through clinical and epidemiologic research. Funded by the National Institutes of Allergy and Infectious Diseases (NIAID) the objectives across the four African IeDEA regions (West Africa Central Africa East Africa and Southern Africa) are similar and cover all populations including pregnant women infants children adolescents and adult patients. They can be summarized as follows: (1) To prove robust evaluation of the delivery of ART in children adolescents and adults in sub-Saharan Africa with a focus on long-term program effectiveness and outcomes; (2) to describe the long-term temporal trends in regimen durability and tolerability and to examine monitoring strategies; (3) to describe important comorbidities and co-infections of HIV infection including malaria tuberculosis and cancer; (4) to examine the pregnancy- and HIV-related outcomes of women initiating ART during pregnancy and of infants exposed to HIV or ART in utero; (5) to develop and apply novel statistical methods to deal with missing data loss to follow-up competing risks and time-dependent confounding; (6) to establish procedures to link the HIV cohort data with other databases at local or national level. The present report provides an indicative summary of some of the major research themes and key findings as well as a discussion of the program’s strengths and weaknesses.

Background Improved primary health care is needed in developing countries to effectively manage the growing burden of hypertension. Our objective was to evaluate hypertension management in Zambian rural primary care clinics using process and outcome indicators to assess the screening, monitoring, treatment and control of high blood pressure. Methods Better Health Outcomes through Mentoring and Assessment (BHOMA) is a 5-year, randomized stepped-wedge trial of improved clinical service delivery underway in 46 rural Zambian clinics. Clinical data were collected as part of routine patient care from an electronic medical record system, and reviewed for site performance over time according to hypertension related indicators: screening (blood pressure measurement), management (recorded diagnosis, physical exam or urinalysis), treatment (on medication), and control. Quantitative data was used to develop guides for qualitative in-depth interviews, conducted with health care providers at a proportional sample of half (20) of clinics. Qualitative data was iteratively analyzed for thematic content. Results From January 2011 to December 2014, 318,380 visits to 46 primary care clinics by adults aged ≥ 25 years with blood pressure measurements were included. Blood pressure measurement at vital sign screening was initially high at 89.1% overall (range: 70.1–100%), but decreased to 62.1% (range: 0–100%) by 48 months after intervention start. The majority of hypertensive patients made only one visit to the clinics (57.8%). Out of 9022 patients with at least two visits with an elevated blood pressure, only 49.3% had a chart recorded hypertension diagnosis. Process indicators for monitoring hypertension were

Objective To describe engagement along the HIV continuum of care using a large network of clinics in Zambia. Methods We employed a practical framework to describe retention along the HIV treatment cascade, using routinely collected clinical data available in resource-constrained settings. We included health facilities in four Zambian provinces with more than 300 enrolled patients over the age of 5 years. We described attrition at each step, from HIV enrolment to 720 days after ART initiation. The population was further stratified by year of enrolment to describe temporal trends in patient engagement. Results From January 2004 to December 2014, 444 439 individuals over the age of 5 years sought HIV care at 75 eligible health facilities. Among those enrolled into HIV care, 82.1% (95% confidence interval [CI]: 79.4–84.5%) were fully assessed for ART eligibility within 180 days of enrolment and 63.6% (95% CI: 61.7–65.3) were found to be eligible for ART based on the HIV treatment guidelines at the time. Of those patients eligible for ART, 81.1% (95% CI: 79.5–82.7%) initiated ART within 180 days. Patient retention in ART programme was 81.2% (95% CI: 80.4–81.9%) at 90 days, 70.0% (95% CI: 68.7–71.2%) at 360 days and 61.6% (95% CI: 60.0–63.2%) at 720 days. We noted a steady decline in proportions assessed for ART eligibility and deemed eligible for ART in the time frame. Proportions that started ART and remained in care remained relatively consistent. Conclusion We describe a simple approach for assessing patient engagement after enrolment into HIV care. Using limited types of data routinely available, we demonstrate an important and replicable approach to monitoring programmes in resource-constrained settings.

Introduction Zambia is facing a chronic shortage of health care workers. The paper aimed at understanding how the Medical Education Partnership Initiative (MEPI) program facilitated strengthening and expanding of the national capacity and quality of medical education as well as processes for retaining faculty in Zambia. Methods Data generated through documentary review, key informant interviews and observations were analyzed using a thematic approach. Results The MEPI program triggered the development of new postgraduate programs thereby increasing student enrollment. This was achieved by leveraging of existing and new partnerships with other universities and differentiating the old Master in Public Health into specialized curriculum. Furthermore, the MEPI program improved the capacity and quality of training by facilitating installation and integration of new technology such as the eGranary digital library, E-learning methods and clinical skills laboratory into the Schools. This technology enabled easy access to relevant data or information, quicker turn around of experiments and enhanced data recording, display and analysis features for experiments. The program also facilitated transforming of the academic environment into a more conducive work place through strengthening the Staff Development program and support towards research activities. These activities stimulated work motivation and interest in research by faculty. Meanwhile, these processes were inhibited by the inability to upload all courses on to Moodle as well as inadequate operating procedures and feedback mechanisms for the Moodle. Conclusion Expansion and improvement in training processes for health care workers requires targeted investment within medical institutions and strengthening local and international partnerships.

The objective of this study was to describe the impact of intense counseling to reduce vaginal hygiene practices and its effect on bacterial vaginosis. A secondary data analysis of the HIV Prevention Trials Network 035 study was undertaken, focusing on HIV-negative, nonpregnant women who were at least 18 years old, in seven African sites and one US site. At enrollment and during follow-up quarterly visits, vaginal hygiene practices were determined by face-to-face administration of a behavioral assessment questionnaire. Vaginal hygiene practices were categorized as insertion into the vagina of (1) nothing, (2) water only, and (3) other substances with or without water. Each practice was quantified by frequency and type/combination of inserted substances. At quarterly visits, diagnosis of bacterial vaginosis was made using the Nugent score. Trends for vaginal hygiene practices and bacterial vaginosis were evaluated using generalized estimating equation models. A total of 3087 participants from the HIV Prevention Trials Network 035 study were eligible for this analysis. At enrollment, 1859 (60%) reported recent vaginal hygiene practices. By one year, this figure had decreased to 1019 (33%) with counseling. However, bacterial vaginosis prevalence remained consistent across the study observation period, with 36%–38% of women testing positive for the condition ( p for trend = 0.27). Overall, those who reported douching with water only (AOR = 1.03, 95%CI: 0.94–1.13) and those who reported inserting other substances (AOR= 0.98, 95%CI: 0.88–1.09) in the past quarter were not more likely to have bacterial vaginosis compared to those who reported no insertions. However, in South Africa, an increase in bacterial vaginosis was seen among those who reported inserting other substances (AOR: 1.48, 95%CI: 1.17, 1.88). In conclusion, targeted counseling against vaginal hygiene practices resulted in change in self-reported behavior but did not have an impact on bacterial vaginosis diagnosis in all but one site.

We analyzed the association of age at antiretroviral therapy (ART) initiation with CD4(+) T cell count recovery, death, and loss to follow-up (LTFU) among HIV-infected adults in Zambia. We compared baseline characteristics of patients by sex and age at ART initiation [categorized as 16-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years and older]. We used the medication possession ratio to assess adherence and analysis of covariance to measure the adjusted change in CD4(+) T cell count during ART. Using Cox proportional hazard regression, we examined the association of age with death and LTFU. In a secondary analysis, we repeated models with age as a continuous variable. Among 92,130 HIV-infected adults who initiated ART, the median age was 34 years and 6,281 (6.8%) were aged ≥50 years. Compared with 16-29 year olds, 40-49 year olds (-46 cells/mm(3)), 50-59 year olds (-53 cells/mm(3)), and 60+ year olds (-60 cells/mm(3)) had reduced CD4(+) T cell gains during ART. The adjusted hazard ratio (AHR) for death was increased for individuals aged ≥40 years (AHR 1.25 for 40-49 year olds, 1.56 for 50-59 year olds, and 2.97 for 60+ year olds). Adherence and retention in care were poorest among 16-29 year olds but similar in other groups. As a continuous variable, a 5-year increase in age predicted reduced CD4(+) T cell count recovery and increased risk of death. Increased age at ART initiation was associated with poorer clinical outcomes, while age30 years was associated with a higher likelihood of being lost to follow-up. HIV treatment guidelines should consider age-specific recommendations.