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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 Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. Methods We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm ( Results 299 women and their newborns were included (146 cases, 153 controls). When compared to women receiving zidovudine alone, those on ART had higher odds of progesterone levels under the 10th percentile (adjusted odds ratio [AOR]:2.34, 95%CI:1.41–3.89) and 25th percentile (AOR:2.07, 95%CI:1.46–2.94). However, higher levels of progesterone—rather than lower levels—were associated with our composite case outcome at the 10th percentile (AOR:1.88, 95%CI:0.77–4.59) and 25th percentile (AOR:1.96, 95%CI:1.06–3.61). Associations were not observed between prolactin, antiretroviral regimen, and birth outcomes. Conclusion We observed lower progesterone levels among women allocated to ART regimens; however, higher progesterone levels were associated with preterm birth and/or low birthweight. While features of the study design may have contributed to these findings, they nevertheless highlight the potentially complex mechanisms underpinning adverse birth outcomes and HIV.

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.

Human immunodeficiency virus (HIV) has a disproportionate effect on pregnant and breastfeeding women in sub-Saharan Africa. This study used egocentric social network analysis (SNA) to compare the social and sexual networks of HIV-negative and HIV-positive women attending an antenatal care (ANC) clinic in Lusaka, Zambia. In order to assess risk and protective factors for HIV acquisition and transmission, variables included self (ego) sociodemographic characteristics, main partner characteristics, features of the relationship between ego and her main partner, alter attributes, alter-ego ties, and alter-alter ties. Associations between the independent variables and ego HIV status were identified using bivariate tests. Logistic regression analyses were performed to assess the relationship between predictors and ego HIV status when multiple variables were included in the same model. Overall, 219 participating women (69 HIV-positive, 150 HIV-negative) nominated 1095 alters. Compared to HIV-negative egos, HIV-positive egos were older, had main partners who were more likely to consume alcohol before sex, disclosed their HIV status to fewer alters, had fewer alters with whom they had daily interactions, and had more alters who were HIV-positive or HIV-unknown. Number of alters who were HIV-positive or HIV-unknown and number of alters to whom participants disclosed their HIV status presented the strongest associations with ego HIV status, with the association between number of HIV-positive or HIV-unknown alters and ego HIV status being of a slightly greater magnitude than non-disclosure of HIV status.

BackgroundThe University of Zambia’s (UNZA) Mentor Training Program, established in 2018, is conducted annually to strengthen the mentorship capacity of the UNZA PhD program for the health professions. This intensive five-session course trains faculty members in the mentorship of students. Established by senior UNZA leaders and US-based collaborators, this program was designed to address gaps in mentorship identified at the institutional level. Faculty facilitators developed the course curriculum and used a train-the-trainer model to ensure program sustainability. Participants were faculty members and current or future mentors of PhD and Master of Medicine students. MethodsTo assess the program’s impact, faculty mentors and their mentees completed a 26-item questionnaire on mentoring competencies at the end of a mentor’s participation in the course and one year later. The competencies included: maintaining effective communication, aligning expectations, assessing understanding, fostering independence, addressing diversity, and promoting professional development. Competency scores were compared longitudinally to quantify potential changes in mentoring behaviors.ResultsMentors and mentees alike noted mentor growth in all competency domains from post-course to one year later, providing evidence that the program may have sustained and positive effects on mentoring behaviors over time. Analysis of mentors’ self-ratings indicated a 20% increase in perceived competency from pre-training to one year later; mentees noted a 7% increase in mentors’ competency during the same period. Salient areas of growth corresponded with topics of emphasis and in-depth discussions in the course, including addressing diversity, aligning expectations, assessing capacities, motivating mentees, and fostering independence. ConclusionsThese findings suggest that mentors internalized this content and transferred it to behavior change. The behavioral changes may reveal a larger change in the institutional environment around the mentoring of students. The UNZA Mentor Training Program appears to have sustained impact after a year and should bode well for future benefits to students, faculty, and the institution.

BACKGROUND: Ultrasound is indispensable to gestational age estimation and thus to quality obstetrical care, yet high equipment cost and the need for trained sonographers limit its use in low-resource settings. METHODS: From September 2018 through June 2021, we recruited 4695 pregnant volunteers in North Carolina and Zambia and obtained blind ultrasound sweeps (cineloop videos) of the gravid abdomen alongside standard fetal biometry. We trained a neural network to estimate gestational age from the sweeps and, in three test data sets, assessed the performance of the artificial intelligence (AI) model and biometry against previously established gestational age. RESULTS: In our main test set, the mean absolute error (MAE) (±SE) was 3.9±0.12 days for the model versus 4.7±0.15 days for biometry (difference, −0.8 days; 95% confidence interval [CI], −1.1 to −0.5; P

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 naive 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.

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.

BackgroundUltrasound is indispensable to gestational age estimation, and thus to quality obstetric care, yet high equipment cost and need for trained sonographers limit its use in low-resource settings.MethodsFrom September 2018 through June 2021, we recruited 4,695 pregnant volunteers in North Carolina and Zambia and obtained blind ultrasound sweeps (cineloops) of the gravid abdomen alongside standard fetal biometry. We trained a neural network to estimate gestational age from the sweeps and, in three test sets, assessed performance of the model and biometry against previously established gestational age.ResultsIn our main test set, model mean absolute error (MAE) was 3.9 days (standard error [SE] 0.12) vs. 4.7 days (SE 0.15) for biometry (difference -0.8 days; 95% CI -1.1, -0.5; pConclusionsOur model estimated gestational age more accurately from blindly obtained ultrasound sweeps than did trained sonographers performing fetal biometry. These results presage a future where all pregnant people – not just those in rich countries – can access the diagnostic benefits of sonography.

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.

To successfully link to care, persons living with HIV must negotiate a complex series of processes from HIV diagnosis through initial engagement with HIV care systems and providers. Despite the complexity involved, linkage to care is often oversimplified and portrayed as a single referral step. In this article, we offer a new conceptual framework for linkage to care, tailored to the current universal test and treat era that presents linkage to care as its own nuanced pathway within the larger HIV care cascade. Conceptualizing linkage to care in this way may help better identify and specify processes posing a barrier to linkage, and allow for the development of targeted implementation and behavioral science-based approaches to address them. Such approaches are likely to be most relevant to programmatic and clinical settings with limited resources and high HIV burden.