Introduction
A vaginal ring containing 25 mg of the antiretroviral dapivirine has demonstrated efficacy in reducing women’s risk of sexually acquiring HIV‐1; however, imperfect ring use likely ...diluted efficacy estimates in clinical trials. The amount of dapivirine remaining in returned rings may reflect the extent of product use, permitting estimation of HIV protection in the context of consistent use.
Methods
We measured the amount of dapivirine in returned rings from a placebo‐controlled trial of the dapivirine vaginal ring conducted between August 2012 and June 2015 among 2629 African women. Phase I/II studies established that greater than 4 mg of dapivirine on average is released from the ring when used consistently over 28 days and ≤0.9 mg released suggested non‐use. We assessed the relative risk reduction associated with levels of ring use using residual dapivirine in returned rings as a time‐dependent covariate for HIV‐1 infection in multivariable Cox models, including multiple exploratory analyses designed to estimate upper limits of efficacy given uncertainty in timing of HIV‐1 acquisition. All models were adjusted for baseline covariates associated with HIV risk and adherence.
Results
Residual dapivirine levels indicating at least some use (>0.9 mg released over a month) were associated with a 48% relative reduction in HIV‐1 acquisition risk (95% confidence interval (CI): 21% to 66%; p = 0.002) compared to the placebo. Exploratory analyses accounting for potential misclassification in timing of HIV‐1 acquisition estimated 75% to 91% HIV‐1 risk reduction with> 4 mg released when compared to placebo. Results limited to the subgroup of women <25 years of age, who tended to have lower adherence, were generally consistent to those overall.
Conclusions
Residual dapivirine levels, an objective measure of adherence, were correlated with HIV‐1 protection in a secondary analysis of a randomized trial. Periods of ring use were associated with approximately 50% protection, with exploratory analyses suggesting higher protection with more consistent use. The dapivirine vaginal ring is the first method to fulfil the promise of a fully reversible, long‐acting, woman‐initiated approach for discreet HIV‐1 prevention.
Purpose of Review
East and Southern Africa are the epicenter of the HIV epidemic. High HIV incidence rates among adolescent girls and young women (AGYW) remain stable over the last decade despite ...access to daily oral PrEP. Some settings have experienced high PrEP uptake among AGYW; however, discontinuation has been high. This review sought to understand drivers of PrEP discontinuation in this population in order to identify potential mechanisms to facilitate PrEP restart and optimize PrEP use.
Recent Findings
Drivers of PrEP discontinuation included low perceived HIV acquisition risk, PrEP-associated side effects, pill burden, family/sexual partner disapproval, lack of/intermittent sexual activity, PrEP use stigma, fear of intimate partner violence, misinformation about long-term PrEP use, and limited/inconsistent access to PrEP.
Summary
The most frequently reported driver of PrEP discontinuation was low perceived HIV acquisition risk. This indicates that innovative interventions to help AGYW recognize their HIV risk and make informed decisions about PrEP use are urgently needed.
Introduction
There is little published literature about gay, bisexual and other men who have sex with men and transgender individuals (MSM and TG)’s use of social media in sub‐Saharan Africa, despite ...repressive social and/or criminalizing contexts that limit access to physical HIV prevention. We sought to describe MSM and TG’s online socializing in Nairobi and Johannesburg, identifying the characteristics of those socializing online and those not, in order to inform the development of research and health promotion in online environments.
Methods
Respondent‐driven sampling surveys were conducted in 2017 in Nairobi (n = 618) and Johannesburg (n = 301) with those reporting current male gender identity or male sex assigned at birth and sex with a man in the last 12 months. Online socializing patterns, sociodemographic, sexual behaviour and HIV‐testing data were collected. We examined associations between social media use and sociodemographic characteristics and sexual behaviours among all, and only those HIV‐uninfected, using logistic regression. Analyses were RDS‐II weighted. Thirty qualitative interviews were conducted with MSM and TG in each city, which examined the broader context of and motivations for social media use.
Results
Most MSM and TG had used social media to socialize with MSM in the last month (60% Johannesburg, 71% Nairobi), mostly using generic platforms (e.g. Facebook), but also gay‐specific (e.g. Grindr). HIV‐uninfected MSM and TG reporting riskier recent sexual behaviours had raised odds of social media use in Nairobi, including receptive anal intercourse (adjusted OR = 2.15, p = 0.006), buying (aOR = 2.24, p = 0.015) and selling sex with men (aOR = 2.17, p = 0.004). Evidence for these associations was weaker in Johannesburg, though socializing online was associated with condomless anal intercourse (aOR = 3.67, p = 0.003) and active syphilis (aOR = 13.50, p = 0.016). Qualitative findings indicated that while online socializing can limit risk of harm inherent in face‐to‐face interactions, novel challenges were introduced, including context collapse and a fear of blackmail.
Conclusions
Most MSM and TG in these cities socialize online regularly. Users reported HIV acquisition risk behaviours, yet this space is not fully utilized for sexual health promotion and research engagement. Effective, safe and acceptable means of using online channels to engage with MSM/TG that account for MSM and TG’s strategies and concerns for managing online security should now be explored, as complements or alternatives to existing outreach.
The monthly dapivirine vaginal ring has proven efficacious in reducing HIV incidence in two Phase 3 clinical trials. When considering the potential future availability of the ring to the public, key ...questions remain about the feasibility of integrating the ring as an HIV prevention intervention into women’s lives. We conducted qualitative mapping interviews (
n
= 66) among women enrolled in MTN-025/HOPE, an open-label trial conducted in Malawi, South Africa, Uganda and Zimbabwe, to examine how home environments influenced use of the dapivirine vaginal ring. Most women had secure places to store their rings including wardrobes, suitcases, and bags. The primary concerns for ring storage were potential tampering from children or rodents. Household overcrowding limited the privacy some women had which made removal and insertion of vaginal rings challenging. Despite these challenges, ring storage, insertion, and removal was feasible across social and living contexts.
Introduction
Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral ...pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.
Methods
ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression.
Results
PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two‐thirds of PrEP users were continuing PrEP at study exit.
Conclusions
There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention.
Understanding characteristics associated with adherence to pre-exposure prophylaxis (PrEP) methods for HIV-1 prevention may assist with optimizing implementation efforts. The dapivirine vaginal ring ...is a novel topical PrEP delivery method. Using data from a randomized, double-blind, placebo-controlled, phase III trial of the dapivirine vaginal ring conducted in four African countries, generalized estimating equation models were used to evaluate correlates of ring adherence. Two levels of quarterly dapivirine blood plasma, and dapivirine released from returned rings defined measures of adherence for recent and cumulative use, respectively. Time on study, calendar time, primary partner knowledge that the participant was taking part in the study, and use of long-acting contraceptive methods were associated with ring adherence whereas younger age, ring worries, condom use, episodes of menstrual bleeding and vaginal washing were associated with non-adherence. These findings may be useful for recruitment into future clinical studies and dapivirine ring implementation efforts.
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.
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.
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.
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.
Globally, young gay, bisexual and other men who have sex with men (YMSM) experience a disproportionate burden of disease compared to young heterosexual men and older MSM. However, YMSM experience ...major inequities in access and use of health services. We sought to gain a detailed understanding of YMSM's healthcare engagement experiences across public, private, tertiary institution-based and MSM-friendly health facilities in Nairobi, Kenya, to inform development of interventions to improve access and use of health services by YMSM.
In September 2021, in-person qualitative in-depths interviews were conducted among 22 YMSM purposively sampled from 248 YMSM who had previously participated in a respondent-driven sampling integrated bio-behavioral survey. Interviews were done in English, transcribed verbatim and analyzed descriptively using NVivo version 12.
Participants were 18-24 years old, all identified as cisgender male, three-quarters as gay and a quarter as bisexual. Themes that were defined from the analysis included: YMSM's experiences during healthcare seeking in various clinical settings, priority health needs, desired healthcare provider (HCP) characteristics, and the potential role of digital health interventions in improving access and use of health services. Participants relayed experiences of prejudice, stigma and discrimination when seeking services in public and institution-based health facilities, unlike in community pharmacies, private and MSM-friendly health facilities where they felt they were handled with dignity. Health needs prioritized by YMSM centered on prevention and control of HIV, sexually transmitted infections (STIs), depression and substance abuse. Participants desired HCPs who were empathetic, non-judgmental and knowledgeable about their unique health needs such as management of anorectal STIs. Participants highlighted the usefulness of digital media in offering telehealth consultations and health education on subjects such as HIV/STIs prevention.
During engagement with healthcare, YMSM experience various barriers that may cause them to postpone or avoid seeking care hence resulting in poor health outcomes. There is need to equip HCPs with knowledge, skills and cultural competencies to enable them offer equitable services to YMSM. Considerations should also be made for use of digital health interventions that may help YMSM circumvent some of the aforementioned barriers to service access and use.
Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status ...delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied.
Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV.
Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% Uncertainty Range (UR): 26-42% in 2021 to 25% 19-34% in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% 63-86% to 58% 47-74%, but incidence remained 4.3-fold 3.3-5.7 that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 3.7-7.3. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 3.6-7.6), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 1.9-3.4 in 2071.
Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.
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