Exploring the feasibility and acceptability of integrating screening for gender-based violence into HIV counselling and testing for adolescent girls and young women in Tanzania and South Africa.

BACKGROUND: Gender-based violence (GBV) undermines HIV prevention and treatment cascades, particularly among women who report partner violence. Screening for violence during HIV testing, and prior to offering pre-exposure prophylaxis (PrEP) to HIV uninfected women, provides an opportunity to identify those at heightened HIV risk and greater potential for non-adherence or early discontinuation of PrEP. The paper describes our experience with offering integrated GBV screening and referral as part of HIV counselling and testing. This component was implemented within EMPOWER, a demonstration project offering combination HIV prevention, including daily oral PrEP, to young women in South Africa and Tanzania. METHODS: Between February 2017 and March 2018, a process evaluation was conducted to explore views, experiences and practices of stakeholders (study participants and study clinical staff) during implementation of the GBV screening component. This article assesses the feasibility and acceptability of the approach from multiple stakeholder perspectives, drawing on counselling session observations (n = 10), in-depth interviews with participants aged 16-24 (n = 39) and clinical staff (n = 13), and notes from debriefings with counsellors. Study process data were also collected (e.g. number of women screened and referred). Following a thematic inductive approach, qualitative data were analysed using qualitative software (NVivo 11). RESULTS: Findings show that 31% of young women screened positive for GBV and only 10% requested referrals. Overall, study participants accessing PrEP were amenable to being asked about violence during HIV risk assessment, as this offered the opportunity to find emotional relief and seek help, although a few found this traumatic. In both sites, the sensitive and empathetic approach of the staff helped mitigate distress of GBV disclosure. In general, the delivery of GBV screening in HCT proved to be feasible, provided that the basic principles of confidentiality, staff empathy, and absence of judgment were observed. However, uptake of linkage to further care remained low in both sites. CONCLUSION: Most stakeholders found GBV screening acceptable and feasible. Key principles that should be in place for young women to be asked safely about GBV during HIV counselling and testing included respect for confidentiality, a youth-friendly and non-judgmental environment, and a functioning referral network.

Disclosure of PrEP use by young women in South Africa and Tanzania: qualitative findings from a demonstration project.

Investigating how young women disclose oral pre-exposure prophylaxis (PrEP) use is important given evidence that disclosure is associated with higher adherence. We report qualitative results on PrEP disclosure among young women in South Africa and Tanzania who participated in a PrEP demonstration project (EMPOWER). In total, 81 in-depth interviews were conducted with 39 young women aged 16-24 years-25 from Johannesburg and 14 from Mwanza-at approximately 3, 6 and/or 9 months post-enrolment. Analysis of data was thematic and inductive. Most Johannesburg participants were students in the inner-city; in Mwanza, all worked in recreational venues, occasionally engaging in sexual transactions with customers. A continuum of approaches was evident. Partner disclosure was common in Johannesburg but less so in Mwanza, where many partners were feared as judgemental and potentially violent. In both sites, participants commonly disclosed to family to secure support, and to friends and work colleagues to advocate about PrEP and encourage uptake among at-risk peers. Adherence clubs appeared helpful in building participants' skills and confidence to disclose, particularly in gender-inequitable sexual relationships. PrEP counselling for young women should focus on strengthening communication skills and helping develop strategies for safe disclosure.

"You talk about problems until you feel free": South African adolescent girls' and young women's narratives on the value of HIV prevention peer support clubs.

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV infection in adolescent girls and young women if used consistently during periods of risk. The EMPOWER study evaluated peer-based clubs incorporating an empowerment curriculum offered to adolescent girls and young women (16-24 years) in South Africa and Tanzania for adherence support. METHODS: Using serial in-depth interviews (n = 33), we assessed the benefits and challenges of club attendance among 13 EMPOWER participants in the Johannesburg site who were randomised to clubs. We used a summary matrix of coded data to support a narrative, case-based analysis. Four case studies are presented. RESULTS: Club participants reported benefits such as increased self-esteem and self-efficacy, reduced isolation, and greater insight into gender-based violence and strategies to address it. Day-to-day PrEP adherence was not the only topic discussed in clubs; participants also appreciated the safe space for sharing problems (such as relationship conflict and PrEP stigma) and found interactive exercises helpful in improving partner communication. CONCLUSIONS: Findings support the use of peer-based clubs using a structured empowerment approach, which may offer valuable PrEP initiation support to adolescent girls and young women in settings with high HIV and gender-based violence prevalence. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202006754762723 , 5 April  2020, retrospectively registered.

"It Was Not My Aim to Sleep There": The Impact of Timing and Location of Sex on Adherence to Coitally-Dependent HIV Pre-exposure Prophylaxis.

The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of 'place' and 'timing' in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products.

From fear to resilience: adolescents' experiences of violence in inner-city Johannesburg, South Africa.

BACKGROUND: For adolescents growing up in poor urban South African settings, violence is often a part of daily life and has lasting effects on physical and mental health outcomes in adulthood. We conducted a qualitative study to document and understand the forms of interpersonal violence experienced by adolescents living in Hillbrow, Johannesburg. In this article, we explore how violence is experienced differently by adolescent boys and girls, how they conceptualise 'dangerous' and 'safe' spaces in their neighbourhood and what gaps exist in available services for youth in Hillbrow. METHODS: The article draws on data collected in the formative phase of the 'Wellbeing of Adolescents in Vulnerable Environments' (WAVE) Study of challenges faced by adolescents (15-19 years) growing up in impoverished parts of five cities. This article reports on analysis using only data from the Johannesburg site. Using both purposive and snowball sampling to select participants, we conducted in-depth interviews (n = 20) and community mapping exercises with female (n = 19) and male (n = 20) adolescents living in Hillbrow, as well as key informant interviews with representatives of residential shelters, CBOs, and NGOs working with youth (n = 17). Transcripts were coded manually and analysed using an inductive thematic analysis approach. RESULTS: Both girls and boys reported high exposure to witnessing violence and crime. For girls, the threat of sexual harassment and violence was pervasive, while boys feared local gangs, the threat of physical violence, and being drawn into substance-abuse. Home was largely a safe haven for boys, whereas for girls it was often a space of sexual violence, abuse and neglect. Some adolescents developed coping mechanisms, such as actively seeking out community theatres, churches and other places of sanctuary from violence. Community-based services and shelters that support adolescents reported a lack of resources, overall instability and difficulties networking effectively. CONCLUSIONS: Adolescents in Hillbrow commonly witnessed and had direct experience of many forms of violence in their environment, and these experiences differed markedly by gender. Interventions that build young peoples' social capital and resilience are essential for reducing violence-related trauma and long-term health and social consequences for adolescents in this community.

Adolescent dating violence prevention programmes: a global systematic review of evaluation studies.

Adolescent dating violence negatively affects millions of young people worldwide. Through a global systematic review, we synthesised evidence from rigorous studies of prevention programmes for adolescent dating violence. Our aims were to: (1) describe the breadth of research in this area and evidence of programme effects, and (2) identify gaps in the evidence base. We included experimental and controlled quasi-experimental programme evaluations, published before Jan 1, 2020, that assessed effects on victimisation or perpetration, or both, in adolescent dating violence and in which at least half of the study population was 10-19 years old. Study design, programme elements, and outcomes were compared between evaluations implemented in high-income countries (HICs) and low-income and middle-income countries (LMICs). 52 evaluations met inclusion criteria, of which 20 (38%) were implemented in LMICs. Evaluations in HICs were more likely to assess effects on adolescent dating violence victimisation and perpetration, rather than just victimisation, than those in LMICs, and they were also more likely to include boys and girls, as opposed to just a single sex. Overall, 26 (50%) of the 52 evaluations reported a significant preventive effect on at least one outcome for adolescent dating violence, of which nine were implemented in LMICs. Across LMICs and HICs, findings suggest research is needed to shed light on how adolescent dating violence prevention programmes work and to identify whether programme effects generalise across different settings, outcomes, and subgroups. TRANSLATIONS: For the Chinese, French and Spanish translations of the abstract see Supplementary Materials section.

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study.

BACKGROUND: As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment. METHODS: We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16-35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067. FINDINGS: 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2·16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4·65%) before PrEP access (adjusted incidence rate ratio [IRR] 0·45, 95% CI 0·25-0·82, p=0·0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5·00 vs 2·29 per 100 person-years; IRR 0·43, 95% CI 0·22-0·88, p=0·012). INTERPRETATION: On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, President's Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency, South African Medical Research Council, and United Nations Population Fund.

Integrating oral PrEP delivery among African women in a large HIV endpoint-driven clinical trial.

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.

Collateral benefits: how the practical application of Good Participatory Practice can strengthen HIV research in sub-Saharan Africa.

INTRODUCTION: The Good Participatory Practice (GPP): Guidelines for Biomedical HIV Prevention Trials, second edition (2011) were developed to provide clinical trial sponsors and implementers with a formal stakeholder engagement framework. As one of the largest African research institutes, Wits Reproductive Health and HIV Institute (Wits RHI) became an early adopter of GPP by implementing its principles within large-scale national and regional clinical trials. This article examines Wits RHI's lessons learned from implementing GPP, its ongoing efforts to institutionalize GPP, and the yet to be realized potential in creating fully sustainable structures for meaningful stakeholder engagement in HIV prevention research, implementation science and beyond. DISCUSSION: For the past seven years, Wits RHI has undertaken both centralized leadership roles in implementing GPP across multi-party regional research consortia as well as overseeing GPP for smaller investigator-driven trials. Through this iterative roll-out of GPP, key lessons have emerged. Obtaining upfront funding to support GPP activities throughout and between the research life cycle, and a trained multi-disciplinary team of GPP practitioners have helped facilitate an enabling environment for GPP implementation. We further recommend formally integrating stakeholder engagement into study documents, including monitoring and evaluation plans with indicators and performance metrics, to assist teams to track and refine their GPP strategies. Finally, institutionalizing resources and supporting organization-wide GPP along with ongoing support can help build efficiencies and maximize economies of scale toward a pragmatic and innovative application of the GPP Guidelines. CONCLUSIONS: Thanks to a growing global network of GPP practitioners and a burgeoning GPP Community of Practice, there has been substantive progress in making GPP an integral component of clinical HIV prevention research. The Wits RHI experience highlights the possibilities and the challenges to translating the GPP principles into concrete practices within specific clinical trials and across a research institute. Realizing the full potential of GPP, including direct and indirect - 'collateral benefits' will require the collective buy-in and support from sponsors, implementers and community stakeholders across the research field. As the HIV prevention research field expands, however, a more conscious and systematic implementation of GPP is timely.

Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Young women in southern Africa have substantial risk of HIV acquisition. Female-controlled biomedical interventions are needed to mitigate this risk. We aimed to assess the safety and efficacy of a pericoitally applied tenofovir 1% gel. METHODS: We did a phase 3, double-blind, randomised, placebo-controlled trial at nine community-based clinical trial sites in South Africa to evaluate the safety and efficacy of tenofovir 1% gel. Sexually active women who were HIV negative and aged 18-30 years were enrolled. Participants were randomly assigned (1:1) using sequential participant numbers to either tenofovir 1% gel or a placebo gel (one dose within 12 h before sex and one dose within 12 h after sex [BAT-24 regimen]), using dynamic permuted block sizes of 8 and 16 within each site. Women received monthly HIV-1 testing, risk reduction support, physical examinations, and product dispensing for up to 27 months. The primary efficacy outcome was incident HIV infection and the primary safety outcome was occurrence of grade 2-4 adverse events, both analysed in the modified intention-to-treat population. To assess the efficacy of tenofovir gel, the cumulative probability of HIV infection was calculated for each treatment using the Kaplan-Meier method. This trial is registered with ClinicalTrials.gov, number NCT01386294. FINDINGS: From Oct 11, 2011, to Aug 29, 2014, 3844 women were screened, 2059 enrolled, and 2029 included in the primary analysis (1032 in the tenofovir group and 1027 in the placebo group); 39 (4%) in the tenofovir group and 36 (4%) in the placebo group were lost to follow-up. 123 HIV-1 infections occurred over 3036 woman-years of observation; 61 in the tenofovir group (HIV incidence 4·0 per 100 woman-years, 95% CI 3·1-5·2) and 62 in the placebo group (4·0 per 100 woman-years, 3·1-5·2; incidence rate ratio [IRR] 0·98, 95% CI 0·7-1·4). A higher incidence of grade 2 adverse events was observed in the tenofovir group than in the placebo group (IRR 1·09, 95% CI 1·0-1·2; p=0·02). The most common grade 2 or higher product-related adverse events were hypophosphataemia (n=22 for tenofovir vs n=22 for placebo), genital symptoms (n=6 for tenofovir vs n=2 for placebo), or elevated transaminases (n=2 for tenofovir vs n=2 for placebo). No product-related serious adverse events were reported, and no differences in product-related adverse events (p=0·78), grade 3 events (p=0·64), or grade 4 events (p=0·74) were observed between treatment groups. INTERPRETATION: Overall, pericoital tenofovir gel did not prevent HIV-1 acquisition in this population of young women at risk of HIV infection in South Africa. Alternate safe and effective products that are less user dependent than this product or do not require high adherence are needed. FUNDING: The US Agency for International Development (USAID), the Bill & Melinda Gates Foundation, and the South African Department of Science and Technology and Department of Health.