Prevalence and factors associated with uptake of pre-exposure prophylaxis amongst women vulnerable to HIV who received HIV antibodies in Antibody Mediated Prevention HVTN703/HPTN081 trial in Harare, Zimbabwe: a cross-sectional study.

Introduction: There is limited evidence on pre-exposure prophylaxis (PrEP) uptake post-trial participation for women vulnerable to HIV. This study investigates the prevalence and factors associated with PrEP uptake post-participation in an HIV prevention trial. Methods: Former Antibody Mediated Prevention (AMP) study participants were invited to the three AMP clinical research sites in Zimbabwe after at least a year of exiting the study. The AMP study evaluated the safety and efficacy of Vaccine Research Center 01 broadly neutralising monoclonal antibody in reducing acquisition of HIV-1 infection in women in sub-Saharan Africa. Participants vulnerable to HIV were enrolled and risk reduction counselling was done throughout study participation. In a cross-sectional study, semi-structured interview administered questionnaires were completed. The primary outcome was uptake of PrEP after the study exit. Results: From February 2022 to August 2022, out of 434 participants enrolled in the AMP study, a total of 298 were invited and 225 participated in the study; 28% made an attempt to access PrEP after study participation, 20% used PrEP at some point after study participation and 15% were on PrEP at the time of questionnaire administration. PrEP uptake was associated with new sexual partners after study participation and higher average number of sexual encounters in the previous month. Challenges faced in accessing PrEP included those related to the health facility, transport problems and stigma. Conclusion: The majority (85%) of former AMP participants were not on PrEP at the time of questionnaire administration. We observed poor uptake of PrEP post-study exit among participants who had received risk reduction counselling through study duration. Measures to improve PrEP uptake should be considered on participants vulnerable to HIV when exiting HIV prevention trials.

Perception of couples' on multipurpose prevention technology attribute choice: the case of MTN 045.

BACKGROUND: Multipurpose prevention technologies (MPTs) are products capable of simultaneously addressing multiple sexual and reproductive health needs such as unwanted pregnancy, STIs including HIV-1, and other reproductive tract infections. MPTs are urgently needed to address the double burden of unplanned pregnancy and HIV. While condoms are currently the only accessible MPTs, they are not solely under a woman's control, and female condoms face limitations due to poor acceptability and high cost. METHODS: We conducted a sub-analysis of qualitative data from 39 couples participating in the MTN 045 study to examine the perception of couples on choice and acceptability of a "2 in 1" MPT that combines HIV and pregnancy prevention. RESULTS: Couples recognized the benefits of MPTs for HIV and pregnancy prevention but perceptions tied to each indication and a novel prevention technology tool raised important concerns relevant to use of future MPTs. In the study, participants' perceptions of MPT use were influenced by pregnancy planning. When the timing was less critical, they prioritized HIV prevention. Misinformation about family planning methods, including MPTs, affected decision-making with potential to hinder uptake of future MPTs. Concerns about side effects, such as weight gain and hormonal imbalances, influenced willingness to use MPTs. CONCLUSION: Addressing the myths and misconceptions surrounding the use of contraceptives is crucial in promoting their acceptance and ultimate use. Strategies for addressing the drawbacks women might experience while using a particular product should be in place as new MPTs progress through the development pipeline and approach roll-out.

"First was to sit down and bring our minds together". A qualitative study on safer conception decision-making among HIV sero-different couples in Zimbabwe.

Decision-making on childbearing and safer conception use in HIV sero-different couples involves an intricate balance of individual desires and perceived HIV acquisition risk. This paper addresses an important knowledge gap regarding HIV sero-different couples' considerations and the relationship and power dynamics involved when deciding to use a safer conception method. Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples, who exited the SAFER study - a pilot study assessing the feasibility, acceptability and cost-effectiveness of a safer conception programme for HIV sero-different couples in Zimbabwe. All couples in SAFER were provided with a choice of safer conception methods and were followed for up to 12 months of pregnancy attempts and 3 months following pregnancy. While couples generally perceived their safer conception discussions to be easy and consensus-driven, the decision-making process also involved complex gender dynamics and trade-offs in relationship power, which resulted in differing interpretations of what constituted a joint or shared couple decision. Participants regarded effective couple communication as an essential component of and precursor to good safer conception conversations and requested additional training in couple communication. Couples relied on information from healthcare providers to kickstart their safer conception discussions. Safer conception programmes should address relationship power imbalances, promote effective couple communication and offer healthcare provider support to enable HIV sero-different couples to make informed choices about conception in a manner that upholds their safety and reproductive autonomy.

Our study explored how HIV sero-different couples in Zimbabwe made decisions on the use of safer conception methods. We interviewed 14 men and 17 women who participated in the SAFER study ­ a pilot study looking at how feasible, acceptable and cost-effective a safer conception programme for HIV sero-different couples is in Zimbabwe. We sought to understand the relationship dynamics, considerations and power trade-offs involved in choosing a safer conception method. Couples reported that their conversations about safer conception were easy and agreeable. At the same time, we found that both gender norms and HIV status shaped the couples' decision-making process, with male gender and partners with an HIV-negative status often having more influence in the final decision of which method to use. Effective couple communication was deemed crucial to support safer conception conversations, with participants requesting additional training in this area. The findings emphasise the importance of providing safer conception methods in a context that addresses power disparities, fosters good communication and includes healthcare providers' support to uphold HIV sero-different couples' reproductive rights and help them achieve their reproductive goals.

"We chose PrEP because I wanted to be sure that this child my wife was going to conceive was indeed mine." Factors influencing the choice of safer conception methods and experiences with its use: a qualitative study among HIV sero-discordant couples in Zimbabwe.

BACKGROUND: Safer conception services are needed to minimize HIV transmission among HIV sero-discordant couples desiring pregnancy. Few studies have evaluated the choices couples make when they are offered multiple safer conception methods or real-world method acceptability. This paper addresses an important knowledge gap regarding factors that influence the choice of safer conception methods, couples' actual experiences using safer conception methods, and why some couples switch safer conception methods. METHODS: Between February and June 2019, we conducted semi-structured in-depth interviews among 14 men and 17 women, representing 17 couples who exited the SAFER study-a pilot safer conception study for HIV sero-discordant couples in Zimbabwe that offered couples a choice of ART with monthly viral load monitoring (ART/VL), oral PrEP, vaginal insemination, and semen washing. All couples in SAFER had used at least two safer conception methods. RESULTS: We found that safer conception method choice often centered around a desire for intimacy, condomless sex, and certainty in the conception process, particularly for men. Method-related attributes such as familiarity, perceived ease of use, side effects, and perceived level of effectiveness in preventing HIV and achieving pregnancy influenced method choice, switching, and satisfaction. Concerns were expressed about each safer conception method and couples were willing to try different methods until they found method(s) that worked for them. The majority of participants reported having positive experiences using safer conception, especially those using ART/VL + PrEP, citing that they were able to attempt pregnancy for the first time with peace of mind and experienced joy and satisfaction from being able to achieve pregnancy safely. CONCLUSIONS: The differences in method preferences and experiences voiced by participants in this study and in other studies from the region point to the importance of having a variety of safer conception options in the service delivery package and addressing concerns about paternity, intimacy, and method-related attributes to enable HIV sero-discordant couples to safely achieve their reproductive goals.

Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

BACKGROUND: Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). METHODS AND FINDINGS: Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

Assessing the acceptability of, adherence to and preference for a dual prevention pill (DPP) for HIV and pregnancy prevention compared to oral pre-exposure prophylaxis (PrEP) and oral contraception taken separately: protocols for two randomised, controlled, cross-over studies in South Africa and Zimbabwe.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women's sexual and reproductive health needs. We will gauge the DPP's acceptability in two cross-over clinical trials. METHODS AND ANALYSIS: PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16-40 years) and Harare, Zimbabwe (n=30, 16-24 years) will be randomised 1:1 to the order of regimens-DPP or two separate tablets-each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024. ETHICS AND DISSEMINATION: PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand's Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences. TRIAL REGISTRATION NUMBERS: NCT04778514, NCT04778527.

Assessing Per-Sex-Act HIV-1 Risk Reduction Among Women Using the Dapivirine Vaginal Ring.

BACKGROUND: Confounding introduced by individuals' sexual risk behavior is potentially a significant source of bias in HIV-1 prevention intervention studies. To more completely account for sexual behaviors when assessing the efficacy of the monthly dapivirine ring, a new longer-acting HIV-1 prevention option for women, we estimated per-sex-act risk reduction associated with product use. METHODS: We conducted a secondary analysis of data from MTN-020/ASPIRE, a phase 3, randomized, placebo-controlled efficacy trial of the dapivirine ring that recruited HIV-uninfected, African women aged 18-45 years. With cumulative sex acts as the time scale, we used multivariable Cox regression with inverse probability of censoring weights to estimate HIV-1 risk reduction associated with a rate of dapivirine release indicative of consistent product use. RESULTS: Women in the dapivirine ring group (n = 1187) had an estimated incidence rate of 2.3 (95% confidence interval [CI], 1.8-3.1) HIV-1 acquisition events per 10 000 sex acts versus 3.6 (95% CI, 2.9-4.4) per 10 000 acts in the placebo group (n = 1187). Dapivirine release indicative of consistent ring use was associated with a 63% (95% CI, 33%-80%) per-sex-act HIV-1 risk reduction. CONCLUSIONS: These results support the efficacy of the dapivirine vaginal ring for HIV-1 prevention and help to inform decision-making for women, providers, and policymakers regarding product use. CLINICAL TRIALS REGISTRATION: NCT01617096.

DELIVER: A Safety Study of a Dapivirine Vaginal Ring and Oral PrEP for the Prevention of HIV During Pregnancy.

BACKGROUND: Pregnancy represents a period of high HIV acquisition risk. Safety data for the monthly dapivirine vaginal ring (DVR) during pregnancy are limited. Here, we report data from the first 2 cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). MTN-042 is being conducted in 3 cohorts beginning with later gestational ages when risks of drug exposure are less. METHODS: Eligible pregnant individuals aged 18-40 years in Malawi, South Africa, Uganda, and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants in cohort 1 initiated product use between 36 weeks 0 days (36 0/7 weeks) and 37 6/7 weeks gestation; participants in cohort 2 initiated product use between 30 0/7 and 35 6/7 weeks gestation. All participants continued product use until delivery or 41 6/7 weeks gestation. Pregnancy outcomes and complications were assessed and summarized using descriptive statistics and compared with local background rates obtained through a separate chart review. RESULTS: One-hundred and fifty participants were enrolled into cohort 1 with 101 randomized to DVR and 49 to TDF/FTC. One-hundred and fifty-seven participants were enrolled into cohort 2 with 106 randomized to DVR and 51 to TDF/FTC. In both cohorts, pregnancy complications were rare and similar to local background rates. CONCLUSION: In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC were used in the third trimester of pregnancy, suggesting a favorable safety profile for both prevention products.

Brief Report: HIV Drug Resistance Assessment Among Women Who Seroconverted During the MTN-025/HOPE Open-Label Extension Dapivirine Vaginal Ring Trial.

BACKGROUND: Clinical trials of dapivirine (DPV) vaginal ring have shown it is safe, effective, and desired by women as an HIV prevention option. The risk of drug resistance is a potential concern for DPV ring users who acquire HIV. We conducted a comprehensive resistance evaluation of plasma samples from the women who seroconverted during the Microbicide Trials Network-025/HIV Open-label Prevention Extension (HOPE) study of DPV ring. METHODS: Plasma collected on the visit at which seroconversion was detected was tested by next-generation sequencing with unique molecular identifiers for non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations (DRM) present at ≥1% frequency. Bulk-cloned plasma-derived recombinant HIV was phenotyped in a TZM-bl-based assay for susceptibility to DPV and other NNRTI. HIV-1 RNA was retrospectively quantified in plasma samples collected before HIV seroconversion. RESULTS: Among 38 participants who seroconverted in HOPE, 7 (18%) had NNRTI DRM detected by next-generation sequencing with unique molecular identifiers including A98G, K103N, V106M, E138A, and V179D. Six of 7 samples with NNRTI DRM had <3-fold reduction in susceptibility to DPV. Only 1 sample with K103N and V179I polymorphism had 9-fold reduction in susceptibility to DPV, but this genotype occurred in an individual who did not use DPV ring, likely indicating transmitted resistance. Detection of NNRTI resistance was not higher in individuals who remained on DPV ring >3 months after acquiring HIV infection. CONCLUSIONS: NNRTI resistance among women who seroconverted during HOPE was infrequent and selection of DPV-specific mutations was not detected. DPV ring is considered a safe and effective option for HIV prevention in women.

High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials.

The Antibody Mediated Prevention (AMP) trials (NCT02716675 and NCT02568215) demonstrated that passive administration of the broadly neutralizing monoclonal antibody VRC01 could prevent some HIV-1 acquisition events. Here, we use mathematical modeling in a post hoc analysis to demonstrate that VRC01 influenced viral loads in AMP participants who acquired HIV. Instantaneous inhibitory potential (IIP), which integrates VRC01 serum concentration and VRC01 sensitivity of acquired viruses in terms of both IC50 and IC80, follows a dose-response relationship with first positive viral load (p = 0.03), which is particularly strong above a threshold of IIP = 1.6 (r = -0.6, p = 2e-4). Mathematical modeling reveals that VRC01 activity predicted from in vitro IC80s and serum VRC01 concentrations overestimates in vivo neutralization by 600-fold (95% CI: 300-1200). The trained model projects that even if future therapeutic HIV trials of combination monoclonal antibodies do not always prevent acquisition, reductions in viremia and reservoir size could be expected.