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.

Women's motivations for participating in the dapivirine vaginal ring open label extension study.

Open-Label Extension (OLE) studies are important in the drug development process and are used to further support the licensing applications and regulatory approvals of products. We aimed to understand why women chose to join the HOPE OLE study - where women were offered the dapivirine vaginal ring after two pivotal trials were completed - through data collected from individual in-depth interviews. Ten women at each of the six HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were enrolled ( = 60).

Extended safety and tolerability of subcutaneous CAP256V2LS and VRC07-523LS in HIV-negative women: study protocol for the randomised, placebo-controlled double-blinded, phase 2 CAPRISA 012C trial.

Introduction: Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV prevention. Animal and human studies have demonstrated that bnAbs which neutralise HIV can prevent infection.

Single-nucleotide polymorphisms in ABC drug transporters alter expression and circulating tenofovir in healthy South African women exposed to pre-exposure prophylaxis.

We investigated if single-nucleotide polymorphisms (SNPs) in ATP-binding cassette (ABC) drug transporters alter gene expression and tenofovir disposition in South African women taking Truvada for HIV prevention. In 393 women, real-time PCR was used to determine the associations between six SNPs in ABC transporter genes, mRNA expression and circulating-tenofovir. Univariable and multivariable analyses showed that CT and TT relative to CC genotypes for the (3463C/T) SNP had significantly higher tenofovir levels.

Experience with Contraceptive Dosage Forms and Interest in Novel PrEP Technologies in Women.

New pre-exposure prophylaxis (PrEP) strategies tailored to the needs and expectations of individuals at risk of HIV acquisition are needed. In the CAPRISA 082 prospective cohort study in KwaZulu-Natal, South Africa, sexually active women aged 18 to 30 reported, through interviewer-administered questionnaires, on their prior contraceptive experience and interest in both approved and potential future PrEP dosage forms (oral PrEP, long-acting injectable PrEP, and PrEP implants) between March 2016 and February 2018. Univariable and multivariable Poisson regression models with robust standard errors were used to detect associations between women's prior and current contraceptive use and interest in PrEP options.

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.

Safety and pharmacokinetics of escalating doses of neutralising monoclonal antibody CAP256V2LS administered with and without VRC07-523LS in HIV-negative women in South Africa (CAPRISA 012B): a phase 1, dose-escalation, randomised controlled trial.

Background: Young women in sub-Saharan Africa continue to bear a high burden of HIV infection. Combination anti-HIV monoclonal antibodies are a potential HIV prevention technology that could overcome adherence challenges of daily oral pre-exposure prophylaxis. In this phase 1 clinical trial we aimed to determine the safety and pharmacokinetic profile of the broadly neutralising monoclonal antibody CAP256V2LS.

Male Partner Opinions of the Dapivirine Vaginal Ring Used During an Open-Label Extension HIV Prevention Trial in KwaZulu-Natal, South Africa.

Background: The dapivirine vaginal ring ("the ring") reduced HIV acquisition by about 35% in phase III trials, with modeling from open-label extension trials estimating 50% HIV protection with consistent use. The ring may be used without male partner knowledge. The Assessment of ASPIRE and HOPE Adherence (AHA) substudy aimed to understand the impact of sociocontextual issues on ring adherence.

Integrating Gender-Based Violence Screening and Support into the Research Clinic Setting: Experiences from an HIV Prevention Open-Label Extension Trial in Sub-Saharan Africa.

HIV and gender-based violence (GBV) are syndemic in sub-Saharan Africa and provision of support for participants who disclose GBV constitutes part of comprehensive care. Consequently, a process was undertaken to develop, implement, and evaluate standard operating procedures (SOPs) in MTN-025/HOPE, a study of the dapivirine vaginal ring for HIV prevention. The SOP was developed using needs assessment surveys in addition to World Health Organization (WHO) guidelines and other literature.

Vaginal microbial shifts are unaffected by oral pre-exposure prophylaxis in South African women.

Vaginal microbiota have been shown to be a modifier of protection offered by topical tenofovir in preventing HIV infection in women, an effect not observed with oral tenofovir-based pre-exposure prophylaxis (PrEP). It remains unclear whether PrEP can influence the vaginal microbiota composition. This study investigated the impact of daily oral tenofovir disoproxil fumarate in combination with emtricitabine for PrEP on the vaginal microbiota in South African women.

Correlates of Dapivirine Vaginal Ring Acceptance among Women Participating in an Open Label Extension Trial.

MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, - 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

Background: HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives.

Prospective study of oral pre-exposure prophylaxis initiation and adherence among young women in KwaZulu-Natal, South Africa.

Introduction: Oral tenofovir disoproxil fumarate/emtricitabine pre-exposure prophylaxis (PrEP), introduced into South Africa (SA) in 2016, has increasingly become part of HIV prevention standard of care. Given the urgent need for increased HIV prevention efforts for young women in SA, we conducted an implementation study to explore oral PrEP initiation and adherence, and the impact of oral PrEP on HIV incidence in this group.

Methods: This prospective cohort study (CAPRISA 082) was conducted at two sites (urban and rural) in KwaZulu-Natal, between March 2016 and February 2018.

Efficacy and Action of the Dapivirine Vaginal Ring as Understood by Women Participating in an Open Label Extension Study.

The concept of efficacy, and how HIV prevention products biologically work can be complex. We report on women's interpretation of efficacy of the dapivirine vaginal ring and how they understood it to work to prevent HIV during the MTN-025/HOPE study through data collected from individual in-depth interviews. Ten women at each of the 6 HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were enrolled (n = 60).

Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.

Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI.

Daily Oral Pre-exposure Prophylaxis (PrEP) Continuation Among Women from Durban, South Africa, Who Initiated PrEP as Standard of Care for HIV Prevention in a Clinical Trial.

HIV incidence among women in Eastern and Southern Africa remains unacceptably high, highlighting the need for effective HIV prevention options, including pre-exposure prophylaxis (PrEP). The Evidence for Contraceptive Options and HIV Outcomes trial offered daily oral PrEP to participants during the latter part of the clinical trial as an additional HIV prevention choice. We explored daily oral PrEP continuation at trial exit among women enrolled from Durban, South Africa who initiated oral PrEP at the trial site.

Ring-ing in the Future: Participant and Male Partner Perspectives Regarding Future Use of the Dapivirine Vaginal Ring for HIV Prevention.

Women account for a disproportionate percentage of new HIV infections in sub-Saharan Africa indicating a need for female-initiated HIV prevention options congruent with their lifestyles. The dapivirine vaginal ring for HIV prevention is one such option. We explored the interest of women, who used this ring during the Microbicide Trials Network's ASPIRE and HOPE studies, in using the ring post-licensure and what they perceived as important considerations for future use.

CAPRISA 018: a phase I/II clinical trial study protocol to assess the safety, acceptability, tolerability and pharmacokinetics of a sustained-release tenofovir alafenamide subdermal implant for HIV prevention in women.

Introduction: Young African women bear a disproportionately high risk for HIV acquisition. HIV technologies that empower women to protect themselves are needed. Safe, potent antiretroviral agents such as tenofovir alafenamide (TAF), formulated as long-acting subdermal implants, offer an innovative solution.

Higher mucosal antibody concentrations in women with genital tract inflammation.

Inflammatory cytokines augment humoral responses by stimulating antibody production and inducing class-switching. In women, genital inflammation (GI) significantly modifies HIV risk. However, the impact of GI on mucosal antibodies remains undefined.

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study.

Background: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs).

Does the Ring Work? Perceptions and Understanding of the Efficacy of a Dapivirine Vaginal Ring for HIV Prevention Amongst Women in a Placebo-Controlled Trial.

As demonstrated by the Phase III clinical trial, MTN-020/ASPIRE, the monthly dapivirine vaginal ring is well tolerated and reduces the risk of HIV-1 as a woman-initiated prevention option. This analysis uses data from the follow-on MTN-032/Assessment of ASPIRE and HOPE Adherence (AHA) qualitative study to understand how perceptions (or misperceptions) of ring efficacy may have influenced behavior during ASPIRE, and affected intention to use the ring in future ring projects, specifically HOPE, the planned open-label extension study. Single in-depth interviews (n = 98) and 12 focus group discussions (n = 89) were conducted with women at seven sites in Malawi, South Africa, Uganda and Zimbabwe.

Using Emoji Stickers to Understand End-User Opinions of the Dapivirine Vaginal Ring for HIV Prevention.

Globally, HIV affects women disproportionally to men, particularly in sub-Saharan Africa. While the monthly dapivirine vaginal ring (VR) is a promising female-initiated HIV prevention method, it is important to understand how well the ring is liked. With former participants of HOPE, an open-label extension trial of the ring, we used emoji stickers and a worksheet to explore female end-user's acceptability of and opinions about the VR.