High recent PrEP adherence with point-of-care urine tenofovir testing and adherence counselling among young African women: results from the INSIGHT cohort.

Introduction: Adolescent girls and young women (AGYW) account for two-thirds of new HIV infections in Africa. African AGYW have had high uptake of oral HIV pre-exposure prophylaxis (PrEP) but low adherence, which might be improved by point-of-care adherence monitoring with tailored counselling.

Methods: From August 2022 to July 2023, we conducted a PrEP demonstration project with sexually active AGYW ages 16-30 years from 20 sites in South Africa, Eswatini, Kenya, Malawi, Uganda and Zambia.

Safety, effectiveness and immunogenicity of heterologous mRNA-1273 boost after prime with Ad26.COV2.S among healthcare workers in South Africa: The single-arm, open-label, phase 3 SHERPA study.

Limited studies have been conducted on the safety and effectiveness of heterologous COVID-19 vaccine boosting in lower income settings, especially those with high-HIV prevalence., The Sisonke Heterologous mRNA-1273 boost after prime with Ad26.COV2.

Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

Background: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women.

Methods: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo.

Safety and pharmacokinetics of subcutaneous administration of broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs), given to HIV-1 exposed, uninfected neonates and infants: study protocol for a phase I trial.

Background: The ambitious goal to eliminate new pediatric HIV infections by 2030 requires accelerated prevention strategies in high-risk settings such as South Africa. One approach could be pre-exposure prophylaxis (PrEP) with broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs). The aim of our study is to define the optimal dose(s), the ideal combination(s) of bNAbs in terms of potency and breadth, and timing of subcutaneous (SC) administration(s) to prevent breast milk transmission of HIV.

Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial.

Background: Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa.

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.

Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015;  = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use.

Patterns of Adherence to a Dapivirine Vaginal Ring for HIV-1 Prevention Among South African Women in a Phase III Randomized Controlled Trial.

Background: Persistent use of HIV prevention methods can be a challenge, particularly for some younger women. The long-acting, discreet, woman-centric dapivirine vaginal ring offers promise as a prevention method with less user burden, which could support continued use. We assessed dapivirine vaginal ring use to understand adherence patterns and identify characteristics influencing patterns.

Infusion Reactions After Receiving the Broadly Neutralizing Antibody VRC01 or Placebo to Reduce HIV-1 Acquisition: Results From the Phase 2b Antibody-Mediated Prevention Randomized Trials.

Background: The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs.

Prevalent human papillomavirus infection increases the risk of HIV acquisition in African women: advancing the argument for human papillomavirus immunization.

Objective: Vaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa.

The Influence of Perceived Dapivirine Vaginal Ring Effectiveness on Social Disclosure and Ring Adherence.

We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring.

Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study.

Background: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation.

Methods: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]).

Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials.

The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise pharmacokinetics and predict HIV-1 neutralisation coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women.

Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.

Objective: We aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities.

Design: Secondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE).

Methods: Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis.

Social harms in female-initiated HIV prevention method research: state of the evidence.

Objectives: Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for 'social harms', generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on social harms within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts.

Impact of Partner-Related Social Harms on Women's Adherence to the Dapivirine Vaginal Ring During a Phase III Trial.

Background: Long-acting female-initiated methods such as the dapivirine ring may give women greater agency in HIV-1 prevention. However, social harms, defined as nonmedical adverse consequences of study participation or dapivirine ring use, may reduce product adherence and consequently HIV-1 protection.

Methods: We assessed whether experiencing social harms from male partners was associated with lower adherence to the dapivirine ring in the MTN-020/ASPIRE trial.

Brief Report: Dapivirine Vaginal Ring Use Does Not Diminish the Effectiveness of Hormonal Contraception.

Objective: To evaluate the potential for a clinically relevant drug-drug interaction with concomitant use of a dapivirine vaginal ring, a novel antiretroviral-based HIV-1 prevention strategy, and hormonal contraception by examining contraceptive efficacies with and without dapivirine ring use.

Design: A secondary analysis of women participating in MTN-020/ASPIRE, a randomized, double-blind, placebo-controlled trial of the dapivirine vaginal ring for HIV-1 prevention.

Methods: Use of a highly effective method of contraception was an eligibility criterion for study participation.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

Background: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.