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Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to "virtually eliminate" pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges – and opportunities – of improving health services for HIV-infected mothers and their children across the region.

AbstractIntroductionFindings from biomedical, behavioural and implementation studies provide a rich foundation to guide programmatic efforts for the prevention of mother‐to‐child HIV transmission (PMTCT).MethodsWe 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 discussionFrom 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.ConclusionsA 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.

AbstractIntroductionPre‐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.MethodsWe 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.ResultsWomen 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.ConclusionsPregnant 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.

AbstractIntroductionCouple HIV testing and counselling (CHTC) is associated with measurable benefits for HIV prevention and treatment. However, the uptake remains limited in much of sub‐Saharan Africa, despite an expanded range of strategies designed to promote access.MethodsFollowing PRIMSA guidelines, we conducted a systematic review to characterize CHTC uptake strategies. Five databases were searched. Full‐text articles were included if they were: conducted in sub‐Saharan Africa during the study period (1980–2019), targeted heterosexual couples, reported at least one strategy to promote CHTC and provided a quantifiable measure of CHTC uptake. After the initial and full‐text screening, key features of the studies were abstracted and synthesized.ResultsOf the 6188 unique records found in our search, 365 underwent full‐text review with 29 distinct studies included and synthesized. Most studies recruited couples through antenatal care (n = 11) or community venues (n = 8) and used provider‐based HIV testing (n = 25). The primary demand creation strategies included home‐based CHTC (n = 7); integration of CHTC into clinical settings (n = 4); distribution of HIV self‐testing kits (n = 4); verbal or written invitations (n = 4); community recruiters (n = 3); partner tracing (n = 2); relationship counselling (n = 2); financial incentives (n = 1); group education with CHTC coupons (n = 1); and HIV testing at other community venues (n = 1). CHTC uptake ranged from negligible to nearly universal.DiscussionWe thematically categorized a diverse range of strategies with varying levels of intensity and resources used across sub‐Saharan Africa to promote CHTC. Offering CHTC within couples' homes was the most common approach, followed by the integration of CHTC into clinical settings. Due to heterogeneity in study characteristics, we were unable to compare the effectiveness across studies, but several trends were observed, including the high prevalence of CHTC promotion strategies in antenatal settings and the promising effects of home‐based CHTC, distribution of HIV self‐tests and integration of CHTC into routine health services. Since 2019, an updated literature search found that combining partner notification and secondary distribution of HIV self‐test kits may be an additionally effective CHTC strategy.ConclusionsThere are many effective, feasible and scalable approaches to promote CHTC that should be considered by national programmes according to local needs, cultural context and available resources.

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 TakeawaysEvaluation 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.

AbstractIntroductionHIV 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.MethodsInterviewers 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.ResultsMost 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.ConclusionsMost 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.

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

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

AbstractIntroductionPregnant 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.

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