Dvora Joseph Davey

Cisgender women face an increased risk of HIV acquisition during pregnancy and postpartum. Oral pre‐exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate (F/TDF) is recommended in pregnancy despite limited published pharmacokinetic (PK) and efficacy data during pregnancy. Altered PK during pregnancy may reduce prophylactic efficacy and necessitate higher adherence. Tenofovir alafenamide (TAF) is a newer tenofovir prodrug with higher tenofovir diphosphate (TFV‐DP) exposure in peripheral blood mononuclear cells (PBMCs), but the prophylactic efficacy of F/TAF across different reproductive stages in women is understudied. We adapted a multiscale modeling framework to predict the prophylactic efficacy of F/TDF and F/TAF across varying adherence levels and during the second trimester, third trimester, and 6–12 weeks postpartum. Clinical trial simulations were conducted utilizing PBMC TFV‐DP and emtricitabine triphosphate concentrations as surrogate markers for F/TAF and F/TDF efficacy. For both F/TDF and F/TAF, prophylactic efficacy was lowest during the second trimester, increased in the third trimester (but remained below nonpregnant levels), and was highest postpartum. At high adherence levels of five or more pills per week, predicted effectiveness remained high across pregnancy and postpartum and effectiveness exceeded 97% for both regimens, with maximum decreases in the second trimester of only 0.9 percent point for F/TDF and 0.3 percent point for F/TAF. These findings suggest that adherence is the primary determinant of PrEP effectiveness during pregnancy and postpartum, while pregnancy‐related PK changes have a limited impact on efficacy.

Background: Effective HIV prevention in South Africa requires implementing pre-exposure prophylaxis (PrEP) service delivery options responsive to adolescents and young people (AYP) with diverse characteristics and needs. We aimed to identify characteristics associated with AYP’s choice of PrEP initiation setting. Methods: Fast-PrEP is an ongoing phase 4 HIV prevention programme in Cape Town, South Africa. Oral PrEP (TDF/FTC) is offered to AYP (15–29 years) within sexual and reproductive health services from four community-based mobile clinics and 12 public primary healthcare facilities. Descriptive statistics and logistic regression models evaluated sociodemographic, behavioural, and clinical factors associated with PrEP initiation from mobile clinics and public health facilities in 13,807 AYP between Aug’22 and Dec’24. Results: Most AYP (70.7%; n = 9760) initiated PrEP from mobile clinics. AYP with more complex healthcare needs, such as pregnancy, parenthood, known sero-different relationships, or currently having STI symptoms, were significantly more likely to use the public health facilities. Both male and female AYP initiating PrEP at mobile clinics had four times the odds of moderate-to-severe depression. Previous PrEP experience was not associated with the choice of PrEP service delivery platform. Conclusions: Our results indicate that offering community-based PrEP alongside public sector facilities increases the reach of a diverse group of AYP who may benefit from PrEP.

Background: Men living with HIV (MLWHIV) in Sub-Saharan Africa are less likely than women to know their HIV status, initiate and remain on antiretroviral therapy (ART), and achieve viral suppression. This reduces healthy lifespans and threatens epidemic control. Treatment as prevention (TasP) or Undetectable=Untransmittable (U=U) messaging could close this gap. We hypothesized that brief, peer-delivered positive U=U messaging could promote uptake of HIV testing services and linkage to care among MLWHIV. Methods: We conducted a pragmatic cluster-randomised controlled trial of peer-delivered U=U messaging on men’s uptake of community-based HIV testing and ART initiation in South Africa’s Eastern Cape and Western Cape provinces. HIV testing service site-days were randomised to U=U or standard-of-care (SoC) messaging. Trained male peers invited adolescent boys 15 and older and adult men in the vicinity of mobile testing sites to test for HIV, using an invitation script and card. Mobile testing site-days were randomised to either U=U or standard-of-care (SoC) invitation scripts and cards. The primary outcome was clinic- or laboratory-confirmed initiation or reinitiation of ART within 30 days of testing, assessed by intent-to-treat analysis. Findings: Between March 31, 2023 and April 30, 2024, testing site-days were randomised to U=U (200 days, 13,331 invitations) or SoC (209 days, 14,285 invitations). We observed initiation or reinitiation of ART within 30 days of testing in 0.03% of in the U=U arm vs. 0.05% men in the SoC arm (difference: -0.019%) Interpretation: A light-touch, behaviourally informed community-based intervention communicating the concept of U=U to men did not increase ART initiations. As reported in previous trials of similar interventions, U=U messaging alone may not be enough to affect linkage to care after receiving an HIV-positive result. Future research should investigate the mechanisms by which U=U messaging influences behaviour including its role in reducing motivational barriers to testing.

Background: Despite the potential of point-of-care (POC) tests to improve maternal and newborn health, implementation in low- and middle-income countries remains inconsistent. POC testing enables rapid, decentralized screening, but barriers across health system, facility, and individual levels may undermine uptake. This review synthesizes evidence on factors influencing the adoption, implementation, and sustainability of POC tests within maternal-child health programmes in low-resourced settings. Methods: A comprehensive search was performed across major bibliographic databases and grey literature sources using Boolean combinations of terms related to POC testing, maternal and newborn health, implementation, and low-resourced settings. Studies were eligible if they reported on adoption, implementation, or sustainability of POC tests for maternal or infant screening or diagnosis in low-resourced contexts. Data were extracted using a structured form capturing study characteristics, test types, and implementation determinants. Thematic analysis combined deductive coding using the Consolidated Framework for Implementation Research (CFIR) domains with inductive identification of cross-cutting themes. Methodological quality was appraised using Joanna Briggs Institute critical appraisal tools. Results: Forty studies from 19 low-resourced settings were included, with most evaluating POC testing for Human Immunodeficiency Virus (HIV), syphilis, and early infant HIV diagnosis, highlighting limited implementation evidence for other essential maternal and newborn diagnostics. Key facilitators of implementation included rapid turnaround time, portability, ease of use, perceived clinical benefit, supportive policy environments, and compatibility with existing workflows. Task-shifting, bundled testing, and integration with routine maternal-child health services supported sustainability. However, common barriers included weak supply chains, vertical funding, limited political will, training gaps, workforce shortages, and fragmented programme delivery. Sociocultural barriers, such as stigma and limited decision-making power among pregnant women, also constrained uptake. Conclusions: Effective implementation of POC tests in low-resourced maternal-child health settings requires system-adapted and people-centred approaches. Strengthened domestic ownership, cross-sector coordination, and integrated service delivery, will be critical to ensure equitable access and achieve global targets, including elimination of vertical transmission of HIV, syphilis, and hepatitis B. Expanded implementation research across a broader range of essential POC diagnostics and diverse geographic and infrastructure contexts is needed. Systematic review registration: PROSPERO CRD420251008480.

Background: Curable sexually transmitted infections (STIs), including Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis, remain highly prevalent among pregnant women in South Africa. Despite poor diagnostic performance in pregnancy, syndromic management remains standard care. Point-of-care (POC) screening enables aetiological diagnosis and same-visit treatment but is not yet included in national guidelines. We conducted a mixed-methods process evaluation to examine determinants of antenatal POC STI screening implementation in public facilities. Methods: This evaluation was embedded within the three-arm Philani Ndiphile randomized trial (March 2021-February 2025) across four public clinics in the Eastern Cape. Screening used a near-POC, electricity-dependent nucleic acid amplification test with a 90-minute turnaround time. Reach, Adoption, Implementation, and Maintenance were assessed using the RE-AIM framework. Quantitative indicators included uptake of screening, treatment, and follow-up attendance. Qualitative data included in-depth interviews with 20 pregnant women and five focus group discussions with 21 research staff and government healthcare workers. The Consolidated Framework for Implementation Research guided qualitative analysis. Findings were integrated using narrative weaving. Results: Screening uptake was high (99.0%), with treatment coverage of 95.2% at baseline and 93.5% at repeat screening. Same-day treatment was lower (50.7% and 69.8%) and varied substantially by facility, reflecting operational constraints including turnaround time, patient volume, infrastructure, and electricity. Attendance was higher when screening was integrated into routine ANC. Women valued screening for infant health, while providers recognised advantages over syndromic management but highlighted workforce, resource, and maintenance constraints. Socioeconomic factors, including transport costs, hunger, and work commitments, influenced retention and waiting. Conclusions: Antenatal POC STI screening was acceptable and achieved high treatment coverage in a research setting. However, same-day treatment was constrained by operational requirements of the testing platform. Scale-up will require workflow integration, strengthened health system capacity, and faster diagnostics suited to routine antenatal care.

Background: The risk of HIV acquisition is heightened during pregnancy and early parenthood with the additional risk of vertical HIV transmission. While recent studies have improved our understanding of PrEP use among pregnant and breastfeeding women, further evidence is needed to inform the design of interventions that support sustained use, especially among young women who are pregnant or parenting. Methods: We analysed data from young women aged 15–29 years who initiated PrEP in an implementation study (FastPrEP) in Cape Town, South Africa. Logistic regression was used to examine the association between pregnancy or parenting status (≥ 1 living child) and PrEP discontinuation at 1- and 4-months post-initiation, based on pharmacy refill data. The primary exposure was currently pregnant or having a child (vs. not); secondary analyses stratified by age (15–24 vs. 25–29 years) among women who were pregnant/parenting. Models were adjusted for age and hypothesised explanatory factors were included in sensitivity analysis: service delivery location, contraceptive use, HIV risk perception, and relationship status. Results: Between August 2022 and June 2024 n = 4,876 young women initiated PrEP; 44% were pregnant/parenting (of which 10% were pregnant), and the median age was 21.6 years (IQR:18–25). At 1-month, women who were pregnant/parenting had higher odds of PrEP discontinuation (aOR:1.30, 95% CI:1.14–1.49). At 4-months this relationship persisted (aOR:1.41, 95% CI:1.12–1.78) compared with non-pregnant/parenting women. Among those pregnant/parenting, younger women (15–24 years) had higher odds of discontinuation at 1-month (aOR:1.31, 95% CI:1.08–1.58) and 4-months (aOR:1.41, 95%CI:1.02–1.96) compared to women aged 25–29. In the fully adjusted multivariable model, receiving PrEP in mobile clinics (aOR:0.71, 95% CI:0.61–0.82) vs. government clinics was associated with lower odds of early discontinuation. Conclusion: Young women who are pregnant/parenting face elevated risk of early PrEP discontinuation. Differentiated, life-stage and youth-responsive interventions, such as counselling, partner involvement, and integration with maternal and child health, or sexual and reproductive health services, are critical to improving PrEP persistence among this priority population. This population should be prioritised in the rollout of long-acting PrEP formulations, which may better align with their needs and reduce the burden of daily adherence.

HIV in South Africa remains highly gendered, with women experiencing nearly twice the burden of men. Pregnant and breastfeeding women (PBFW) face elevated HIV acquisition risk, and incident maternal HIV infection during these periods increases the likelihood of vertical HIV transmission. Male partners play a critical role in supporting PBFW to initiate and persist on oral pre-exposure prophylaxis (PrEP), yet limited evidence exists on how best to foster partner support. We conducted in-depth interviews with male partners of PBFW enrolled in a randomized trial (SCOPE-PP) that offered real-time biofeedback counselling on PrEP adherence and access to HIV self-testing (HIVST) in both study arms. Eligible male partners of participants in the intervention arm were invited to participate in November-December 2024. A thematic approach explored men’s perceptions of and support for their partners’ PrEP use. We completed sixteen interviews. Median relationship length was six years; four partners were married to the index participant. All PBFW were taking PrEP at the time of the interview. Men generally held positive views of PrEP, describing it as protective for both mother and infant. Many provided emotional encouragement or practical support. Open communication helped resolve initial mistrust or gendered assumptions that women’s PrEP use signaled suspicion of male infidelity. Exposure to PrEP also prompted men to reflect on their own HIV prevention needs. Findings underscore the value of approaches that center communication within couples to strengthen disclosure and male engagement in PrEP uptake and adherence during the perinatal period and to promote shared responsibility for HIV prevention within families.

Background: In South Africa, pregnant and lactating women (PLW) face a dual burden of high alcohol use and HIV prevalence, both of which adversely affect maternal and infant health. However, few interventions address alcohol use and HIV risk concurrently in this population. Objective: This study seeks to adapt and pilot-test in a randomized controlled trial (RCT) the peer-led multisession intervention Mentor Mothers Plus (MM+) to integrate alcohol reduction strategies with HIV prevention and care support (in a seroneutral intervention) among PLW in Saldanha Bay, Western Cape, South Africa. Methods: Using the ADAPT-ITT (assessment, decision, adaptation, production, topical experts, integration, training, testing) framework, we adapted the evidence-based Mentor Mother (MM) model, originally aimed at reducing vertical HIV transmission among mothers with HIV. Our mixed methods design includes (1) qualitative research, including in-depth interviews (IDIs) and focus group discussions (FGDs), to assess drivers of perinatal alcohol use and HIV risk; (2) intervention adaptation through community-based participatory workshops with stakeholders to refine the MM+ intervention in order to include culturally and contextually strategies; and (3) a pilot RCT with 100 pregnant women (≥16 years old, reporting recent alcohol use) randomized in a 1:1 ratio to the MM+ intervention (motivational interviewing [MI], including HIV and alcohol reduction messaging) or enhanced standard of care (SOC). Primary RCT outcomes include reduced alcohol use, via phosphatidylethanol (PEth) blood levels at 6-month follow-up. Secondary outcomes include uptake and adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) among women with HIV, as well as intervention fidelity, feasibility, and acceptability. Results: Community research included 2 FGDs with health workers (n=6) and community leaders (n=7) and 31 interviews with partners and peers of PLW. Data showed that women are motivated to reduce alcohol use for child health but face barriers (eg, misconceptions about safety of alcohol use, poverty, trauma, and intimate partner violence [IPV]). Alcohol use is with friends/family members/partners and tied to financial stress, unplanned pregnancy, and poor mental health. MM+ support preferences emphasize nonjudgmental, peer-based mentorship, family involvement, and faith/community engagement. Gaps include stigma around HIV and contraceptive services. Communities recommend mentor mothers with lived experience, providing culturally relevant, empathetic support, and linking to social and clinical services. In August 2025, a community workshop refined the intervention, emphasizing the need for trustworthy mentor mothers with lived experience. Priorities included culturally relevant information on alcohol use, HIV prevention, family planning, trauma and interpersonal violence support, and flexible delivery. Next steps involve finalizing materials, training mentor mothers, and launching the RCT. Conclusions: Our community-based, participatory study, MM+, offers a promising approach to address co-occurring alcohol use and HIV among PLW. Stakeholder engagement enhances contextual relevance and supports future scalability. The RCT will evaluate efficacy of the model in reducing alcohol and improving HIV outcomes. Trial Registration: Clinicaltrials.gov NCT06962592; https://clinicaltrials.gov/study/NCT06962592 International Registered Report Identifier (IRRID): DERR1-10.2196/78856