Explore the vast range of titles available.

This study examines qualitative acceptability of the dapivirine vaginal ring (DVR) and oral daily pre-exposure prophylaxis (PrEP) among breastfeeding persons participating in Microbicide Trials Network 043/B-PROTECTED, a phase 3B safety and drug detectability study of DVR and oral PrEP in breastfeeding. A subsample of 52 participants were purposively sampled to participate in an in-depth interview (IDI). Breastfeeding participants found both study products to be acceptable, and easy to use. A common motivation for product use was to protect the baby from HIV, although participants’ understanding of how the study drug would work to protect their babies was often unclear. While most participants did not report experiencing side effects, fears about side effects were common as both initial worries about how the study products would affect their health and the health of their baby, and increased anxiety that health issues experienced by them, or their baby were from the products.

Effective use of oral pre-exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in Eastern and Southern Africa, partly due to stigma and opposition from key influencers. Understanding AGYW’s experiences of disclosure of different PrEP modalities to key influencers may inform strategies to motivate uptake and adherence. We analyzed qualitative in-depth interviews and focus group discussions data from 119 participants in the MTN-034/REACH (Reversing the Epidemic in Africa with Choices in HIV Prevention) study of oral PrEP and the dapivirine vaginal ring (ring) to explore AGYW’s disclosure experiences. We found that AGYW disclosure experiences varied across influencers and product type. The ring was disclosed less often to most influencers, except partners, because it was discreet. Oral PrEP was disclosed more often, because pills were more common and to avoid HIV stigma given that oral PrEP resembled HIV treatment. Ultimately, disclosure typically led most key influencers to support product use through reminders and encouragement. While disclosure yielded positive support from influencers, further community awareness of both PrEP products is essential to reduce potential opposition and perceived stigma.Clinical Trial Number: NCT03593655.

Background Barriers and challenges associated with daily oral HIV pre-exposure prophylaxis (PrEP) contribute to poor uptake, low retention, and adherence rates among youth. Offering a choice of PrEP modalities integrated with peer support and delivered through community-based sexual and reproductive health (SRH) services will overcome these challenges. We describe the design of a trial to evaluate this approach at a population level. Methods We are conducting a type 1a hybrid effectiveness, phase 3B, cluster randomised controlled trial (LAPIS) to evaluate the effectiveness and implementation of offering PrEP modality choices through community-based SRH services amongst youth aged 15–30 years living in rural Kwa-Zulu Natal, South Africa. LAPIS is nested within Thetha nami ngithethe nawe (Let’s Talk), an ongoing stepped-wedge trial with two periods investigating the effectiveness, implementation, and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and SRH services on the population prevalence of sexually transmissible HIV amongst youth. In the second period of Thetha nami , 40 trial clusters were randomised 1:1 to receive either a choice of PrEP modalities (oral PrEP, long-acting PrEP, i.e., two-monthly injectable cabotegravir (CAB LA) or dapivirine vaginal ring and HIV post-exposure prophylaxis [PEP] packs) or enhanced standard of care (ESoC) with oral PrEP only. All trial clusters are supported by peer navigators offering peer support and visited monthly by a mobile nurse-led clinic offering adolescent and youth-friendly HIV and SRH services. There are two primary outcomes: (1) effective uptake of PrEP or PEP, and (2) retention on PrEP, defined as attending at least one follow-up appointment after PrEP/PEP initiation, which are based on clinic data. Implementation outcomes are assessed using a mixed-methods and process evaluation following the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework. Discussion LAPIS is a pragmatic trial to evaluate the addition of long-acting PrEP modalities to daily oral PrEP within community-based SRH services. By offering PrEP choices, LAPIS adopts a person-centred approach to improve adherence and retention among youth, including hidden key populations. Findings will provide insights into the real-world implementation of CAB-LA. Trial registration ClinicalTrials.gov Identifier—NCT06250504. Registered: 01 February 2024.

To research the synergistic activity of G2-S16 dendrimer and dapivirine (DPV) antiretroviral as microbicide candidate to prevent HIV-1 infection. We assess the toxicity of DPV on cell lines by MTT assay, the anti-HIV-1 activity of G2-S16 and DPV alone or combined at several fixed ratios. Finally, their ability to inhibit the bacterial growth was assayed. The analysis of combinatorial effects and the effective concentrations were performed with CalcuSyn software. Our results represent the first proof-of-concept study of G2-S16/DPV combination to develop a safe microbicide.

Abstract Background Postmenopausal women have unique sociobiological human immunodeficiency virus (HIV) risks. We evaluated the safety, pharmacokinetics, and acceptability of a microbicide dapivirine (DPV) vaginal ring (VR) versus placebo in postmenopausal women. Methods We enrolled 96 HIV-negative postmenopausal US women in a phase 2a double-blind, randomized (3:1) trial of monthly VRs containing 25 mg DPV or placebo used continuously for 12 weeks. We assessed safety by adverse events (AEs). DPV concentrations were quantified in plasma and vaginal fluid. Steady-state concentrations were analyzed at 4, 8, and 12 weeks using repeated measures ANOVA. We assessed acceptability by self-report. Results We found no differences in the proportion of women with related grade 2 or higher reproductive system AEs (DPV: 6/72 (8%), placebo: 3/24 (13%), P = .68) or grade 3 or higher AEs (DPV: 4/72 (6%), placebo: 0/24 (0%), P = .57). In the DPV arm, 2/72 (3%) declined to resume product use due to AEs. Median DPV concentrations in plasma (262.0 pg/mL at week 12) and vaginal fluid (40.6 ng/mg at week 12) were constant over 12 weeks and exceeded the in vitro 50% effective concentration by 5000-fold in vaginal fluid by week 4. VR acceptability was high; 84/93 (90%) “very much liked or liked” the VR. Conclusions DPV VRs were safe, well tolerated, and acceptable in postmenopausal women. Plasma concentrations were comparable to published data on DPV use in reproductive-age women (median plasma concentration: 264 pg/mL). Given the reassuring safety and pharmacokinetic data, the DPV VR is promising for preexposure prophylaxis in postmenopausal women. Clinical Trials Registration NCT02010593. Dapivirine vaginal rings are safe, well tolerated, and acceptable in postmenopausal women with dapivirine concentrations comparable to reproductive-age women. Given the reassuring safety and pharmacokinetic data, dapivirine rings show potential as an option for HIV preexposure prophylaxis in postmenopausal women.

Although vaginal microbicides for HIV prevention are designed to be female-initiated, male partner influence has been identified as one of the most significant factors impacting women’s willingness and ability to use them. As a result, research teams have sought to increase male partner involvement by encouraging disclosure of product use to male partners, promoting male partner engagement in the study through attendance at the study clinic, and helping women to garner male partner support for product use. This paper aims to assess the impact of these three elements of male partner involvement on women’s adherence to the dapivirine vaginal ring during MTN-020/ASPIRE, a phase III randomized placebo-controlled clinical trial involving 2629 women in Malawi, South Africa, Uganda, and Zimbabwe. During the study, 64–80% of participants reported disclosure of ring use at each quarterly visit, and 13% reported that their partners had attended the study clinic at some point during the study. At study exit, 66% reported that their partner was supportive, 18% unsupportive, and 17% were unsure. After adjusting for age, site and time in study, women were more likely to have low ring adherence if they had an unsupportive male partner (aRR 1.29, 95% CI 1.03–1.62). Neither disclosure nor clinic attendance directly predicted ring adherence, but disclosure increased the probability of having a supportive partner (aRRR 24.17, 95% CI 16.38–35.66) or an unsupportive partner (aRRR 4.10, 95% CI 2.70–6.24), relative to an unknown level of partner support. Women were also more likely to have a supportive partner if their partner had attended the clinic (aRRR 3.77, 95% CI 1.36–10.42). This study suggests that although the vaginal ring is relatively discreet, lack of support from male partners remains a relevant barrier to use. Though both disclosure and clinic attendance may increase partner support, disclosure may also increase partner opposition. Interventions to reduce male partner opposition are needed to maximize the potential impact of the ring and other PrEP products for HIV prevention.

Breast cancer is the most common cancer in women worldwide. Many breast cancers originate from the cells lining the milk duct and some become invasive. Breast cancer lacking estrogen, progesterone receptors (ER-, PR-) and epidermal growth factor receptor 2 (HER2-) amplification, termed “Triple negative” (TNBC) is reported to frequently affect Black women and younger women. TNBC is an invasive ductal carcinoma with limited treatment options. To this end, we opted to investigate drugs that could be repurposed because they offer advantages in bringing effective treatments faster to the clinic. We chose to study the effect of the drug, dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV because it could be detected in the breast milk of lactating women when treated for HIV and the drug could potentially target the cancer. Here we show the potent impact of dapivirine on MDA-MB-231 TNBC cells, while NNRTI like nevirapine showed marginal effects. When dapivirine was tested on other breast cell lines, MCF-7 and MCF 10A, the inhibition was at higher concentrations. Molecular studies with dapivirine in TNBC cells, revealed an increase in reactive oxygen species (ROS), apoptotic cells, and activation of caspases. Importantly, protein profiling and STRING analysis revealed deregulation of the key molecule, PCNA and impact on pivotal cell signaling circuits including extracellular matrix (ECM), angiogenesis, cell adhesion, and immunomodulation. Of note, is its potential effect on stem-like cells due to downregulation of the basic transcription factor 3 (BTF3) and proteasome activator complex subunit 3; the latter affecting their dependence on the proteasome pathway. Taken together, dapivirine exhibits the potential to be considered as a repurposed drug for TNBC as monotherapy/combination therapy. Notably, it could also potentially be a treatment for individuals with dual ailments, such as HIV and TNBC, if the clinical outcomes with dapivirine for TNBC become favorable.

The Microbicide Trials Network 042 study (MTN-042/DELIVER) is a two-arm, randomized, open-label Phase 3b trial that is evaluating the safety, adherence, and acceptability of the monthly ring and daily oral PrEP among HIV-uninfected pregnant people in four African countries. This analysis focuses on acceptability data captured qualitatively from a subset (n = 48) of the 150 people in the first cohort of the trial who were enrolled in late-stage pregnancy at 36 to 38 weeks gestational age and followed until after delivery. Single IDIs were conducted by trained interviewers at each clinic site using a semi-structured guide. Data excerpts of key codes pertaining to acceptability, pregnancy, and maternal health were summarized, reviewed and interpreted by multinational analyst teams. Although the product use period was relatively short, the data suggested several acceptability findings that may directly translate to longer durations of product use in pregnancy. The first was the overarching maternal sentiment that being able to protect both oneself and their baby was highly valued. The second was the importance of counseling support from providers not only because participants used methods that might generate side effects, but because pregnancy itself is a period with its own set of side effects. The third was that, similar to non-pregnant participants in other trials, here study products were generally liked and described as easy to use. Concerns about ring and oral PrEP use could be addressed with provider counseling and support and should form an essential component rollout among pregnant people.

Longer acting HIV pre-exposure prophylaxis (PrEP) products are effective options for HIV prevention that require less user-dependence. As programs are preparing to launch delivery of these longer acting products, it is important to understand users’ needs and preferences. We conducted a cross-sectional study among women seeking services at 12 family planning clinics in Kisumu, Kenya. Participants were sexually active HIV-negative women ≥15 years, with at least one characteristic that is more common among women who acquire HIV. We assessed PrEP product preferences among PrEP-experienced and inexperienced women. We used descriptive statistics to summarize participants’ characteristics, product preferences, and willingness to use different PrEP modalities. We used univariate and multivariate models to assess factors related to preferences for injectable PrEP. A total of 457 participants were enrolled, including 341 with no oral PrEP experience and 116 with recent oral PrEP experience. The median age was 26 [IQR:23-30], 83% were married or cohabiting and 31% reported using injectable contraceptives. Among participants without prior PrEP experience, 74% preferred injectable PrEP, 19% preferred oral PrEP, and 4% preferred the vaginal ring. Among previous oral PrEP users, 82% preferred injectable PrEP, 16% preferred oral PrEP, and only 2% preferred the dapivirine vaginal ring. Only perceived PrEP stigma was significantly associated with injectable PrEP preference (PR: 1.21, 95% CI 1.09, 1.37, P=0.001). Reproductive-age women in Kenya have a strong interest in long-acting injectable PrEP. Product rollout and implementation needs to consider women’s preference and devise best approaches to deliver injectable PrEP.

Background/aims The dapivirine vaginal ring is a self-administered, women-initiated, discreet, long-acting HIV-1 prevention option for women. It was found to be safe and effective in healthy HIV-negative women who adhered to product use instructions, and has been approved for use in women aged 18 and older in some African countries. A qualitative study was conducted to explore participants’ and their male partners’ discussions on accidental/purposeful vaginal ring removals during The Ring Study (IPM 027 clinical trial). Methods Data were collected via in-depth interviews and focus group discussions with female trial participants and their male partners, from seven research centres in South Africa and Uganda. Data were thematically analysed using NVivo. Results More participants reported purposeful ring removals than accidental expulsions. Various factors influenced purposeful ring removal – including individual (discomfort during use/sex and to clean it), partner (to show them, because of discomfort during sex, to test if partners could feel it, and concerns of harm), organisational (doctor’s request), and socio-cultural (rumours about sickness and infertility). Some described their own ring use removal, others discussed why other participants removed their rings. Conclusions Vaginal ring adherence is critical to improve and support product efficacy. Counselling on vaginal anatomy, vaginal ring insertion and importance of adherence is important to minimise vaginal ring removal. Couples counselling is also important to facilitate support and long-term vaginal ring adherence behaviour. Understanding factors influencing vaginal ring adherence is important for tailoring and targeting messages to support correct and consistent vaginal ring use as it is made available to the public.