Pre-exposure prophylaxis (PrEP) in an era of stalled HIV prevention: Can it change the game?

Pre-exposure prophylaxis (PrEP) for HIV prevention has evolved significantly over the years where clinical trials have now demonstrated the efficacy of oral PrEP, and the field is scaling-up implementation. The WHO and UNAIDS have made PrEP implementation a priority for populations at highest risk, and several countries have developed guidelines and national plans accordingly, largely based on evidence generated by demonstration projects. PrEP presents the opportunity to change the face of HIV prevention by offering a new option for protection against HIV and disrupting current HIV prevention systems. Nevertheless, as with all new technologies, both practical and social requirements for implementation must be taken into account if there is to be sustained and widespread adoption, which will also apply to forthcoming prevention technologies. Defining and building success for PrEP within the scope of scale-up requires careful consideration. This review summarises where the PrEP field is today, lessons learned from the past, the philosophy and practicalities of how successful programming may be defined, and provides perspectives of costs and affordability. We argue that a successful PrEP programme is about effective intervention integration and ultimately keeping people HIV negative

Protocol for a systematic review: understanding the motivations and barriers to uptake and use of female-initiated, primary biomedical HIV prevention technologies in sub-Saharan Africa.

BACKGROUND: Women in sub-Saharan Africa are disproportionately affected by high rates of HIV, yet relatively few products exist for female-initiated HIV prevention. New antiretroviral (ARV)-based prevention options could present opportunities for women to expand their HIV prevention choices; however, acceptability and adherence play a key role in the effectiveness of these products and implementation is still in early stages. To better understand which HIV prevention options might best serve women in sub-Saharan Africa, how and why, this review will explore qualitative evidence from clinical trials and implementation studies alike using a meta-ethnographic approach to synthesise data and interpret results. METHODS/DESIGN: This systematic review will use a meta-ethnographic approach to analyse qualitative data extracted from multiple studies featuring actual use of female-initiated technologies for HIV prevention. The search strategy will be applied in seven databases and papers will be selected using strict inclusion and exclusion criteria. The review will closely follow the guidance set forth by preferred reporting items for systematic reviews and meta-analyses (PRISMA) and Centre for Reviews Dissemination (CRD) where the guidance applies to qualitative data. Two reviewers will review all papers during the paper selection phase, with consultation from a third reviewer to confirm consensus. All papers included in the review will be read and analysed by two reviewers. The final analysis will be conducted by three primary reviewers with additional input from all other authors. DISCUSSION: With new HIV prevention technologies currently in early implementation phases and still more on the horizon, there is much to learn about how best these products may be delivered. A review such as this could help to inform the real-world implementation of the next wave of new HIV prevention technologies such as ARV-based oral pre-exposure prophylaxis (PrEP)

Exploring acceptability of oral PrEP prior to implementation among female sex workers in South Africa.

INTRODUCTION: Female sex workers (FSWs) are at high-risk for HIV acquisition in South Africa, where the advent of new HIV prevention and treatment interventions represent the potential to significantly impact the epidemic. This paper focuses on aspects of PrEP acceptability as a new intervention within the context of a larger service delivery programme including the simultaneous rollout of early ART. This paper explores PrEP acceptability among the FGD participants as future potential users. METHODS: FGDs were conducted in two clinic-based sites in Johannesburg and Pretoria. They aimed to explore community-level, multi-dimensional acceptability of PrEP within the context of imminent implementation alongside early ART in the TAPS Demonstration Project. Sex worker peer educators recruited participants from varying sex work locales. Facilitation was in English with adaptation by facilitators into local languages as needed. Transcripts were translated and transcribed into English. Thematic analysis was used to analyse the data. RESULTS: Four FGDs were conducted in each site for a total of eight FDGs and 69 participants. Demographics were largely similar across the sites. Overall, there was strong acceptability of PrEP among participants and positive anticipation for the imminent delivery of PrEP in the local sex worker clinics. Themes arising from the discussions exploring aspects of PrEP acceptability included: awareness and understanding of PrEP; PrEP motivations including choice, control, and vulnerability, managing PrEP risks and worries; and, de-stigmatizing and empowering PrEP delivery. Participant discussions and recommendations highlighted the importance of developing clear education and messaging to accurately convey the concept of PrEP, and intervention integration into supportive and tailored services. CONCLUSIONS: Through the course of these FGDs, PrEP became a positive and highly anticipated prevention option among the FSWs participants who endorsed implementation in their communities. Effective integration of PrEP into existing services will include comprehensive health programming where ART is also available, appropriate messaging, and support

Treatment And Prevention for female Sex workers in South Africa: protocol for the TAPS Demonstration Project.

INTRODUCTION: Updated guidelines from the WHO recommend antiretroviral treatment for adults with HIV at any CD4 count and daily oral pre-exposure prophylaxis (PrEP) for people at substantial risk of HIV infection. However, implementation challenges may hinder the ability of programmes to translate these recommendations into successful practice. This demonstration project is the first to integrate PrEP and immediate treatment (ITx) for female sex workers (FSWs) in South Africa to answer operational research questions. METHODS AND ANALYSIS: This is a prospective cohort study where the main outcome is retention at 12 months. The study population is recruited into two arms across two urban sites: (1) PrEP for HIV-negative FSWs (n=400) and (2) ITx for HIV-positive FSWs with CD4 greater than national guidelines (n=300). We investigate process and other health indicators, uptake and use of PrEP and ITx through qualitative research, and evaluate cost-effectiveness analysis combined with estimates of impact through epidemiological modelling. ETHICS AND DISSEMINATION: The Treatment And Prevention for female Sex workers in South Africa (TAPS) Project was designed as an implementation study before emtricitabine/tenofovir disoproxil fumarate was licenced as an indication for PrEP in South Africa. Therefore, clinical trial requirements for ethical and South African Medicines Control Council approvals were followed. Results will be disseminated to participants, local health officials and other stakeholders, as well as in peer-reviewed journals and at conferences

Designing PrEP and early HIV treatment interventions for implementation among female sex workers in South Africa: developing and learning from a formative research process.

OBJECTIVES: The objective of this research was to design relevant, tailored oral pre-exposure prophylaxis (PrEP) and early antiretroviral (ART) interventions for female sex workers (FSWs) in South Africa. This paper examines the methods, process and outcomes of employing an inductive approach to formative research exploring intervention feasibility and acceptability. SETTING: Research was conducted in several sex work-related settings including five sites in and around clinics and stakeholder offices. PARTICIPANTS: Participants in this research included stakeholders, experts in the field and FSWs. This included at least 25 separate engagements, 14 local organisations and 8 focus group discussions (FGDs) with 69 participants, in addition to ad hoc meetings. RESULTS: The first set of outcomes consisted of five selected methods: (1) stakeholder consultations; (2) site assessments and selection; (3) field observations and mapping; (4) development of supportive structures to encourage retention and intervention adherence; (5) FGDs conducted with FSWs to explore specifics of acceptability. In terms of feasibility, two sites were selected in central Johannesburg and Pretoria out of five considered. The urban site contexts varied, necessitating adjustments to intervention implementation. There was overall support for PrEP and early ART from stakeholders and FSWs. Concerns included potential issues with adherence to PrEP (and early ART), possible reduction in condom use, resistance to antiretrovirals and burden on scarce resources. These concerns indicated where special attention should be focused on education, messaging and programming as well as development of supportive structures. CONCLUSIONS: The inductive approach allowed for a wide range of perspectives, defining population needs and accessibility. This research illustrated how similar sex work environments can vary and how implementation of interventions may not be uniform across contexts. Lessons learnt in details could assist in future project designs and implementation of new interventions where feasibility, social and cultural factors affecting acceptability must be considered

Preferences for ARV-based HIV prevention methods among men and women, adolescent girls and female sex workers in Gauteng Province, South Africa: a protocol for a discrete choice experiment.

INTRODUCTION: For the past few decades, condoms have been the main method of HIV prevention. Recent advances in antiretroviral (ARV)-based prevention products have substantially changed the prevention landscape, yet little is known about how popular these products will be among potential users, or whether new methods might be used in conjunction with, or instead of, condoms. This study will use a discrete choice experiment (DCE) to (1) explore potential users' preferences regarding HIV prevention products, (2) quantify the importance of product attributes and (3) predict the uptake of products to inform estimates of their potential impact on the HIV epidemic in South Africa. We consider preferences for oral pre-exposure prophylaxis; a vaginal microbicide gel; a long-acting vaginal ring; a SILCS diaphragm used in concert with gel; and a long-acting ARV-based injectable. METHODS AND ANALYSIS: This study will gather data from 4 populations: 200 women, 200 men, 200 adolescent girls (aged 16-17 years) and 200 female sex workers. The DCE attributes and design will be developed through a literature review, supplemented by a thematic analysis of qualitative focus group discussions. Extensive piloting will be carried out in each population through semistructured interviews. The final survey will be conducted using computer tablets via a household sample (for women, men and adolescents) and respondent-driven sampling (for female sex workers), and DCE data analysed using a range of multinomial logit models. ETHICS AND DISSEMINATION: This study has been approved by the University of the Witwatersrand Human Research Ethics Committee and the Research Ethics Committee at the London School of Hygiene and Tropical Medicine. Findings will be presented to international conferences and peer-reviewed journals. Meetings will be held with opinion leaders in South Africa, while results will be disseminated to participants in Ekurhuleni through a public meeting or newsletter

The cost-effectiveness of multi-purpose HIV and pregnancy prevention technologies in South Africa.

INTRODUCTION: A number of antiretroviral HIV prevention products are efficacious in preventing HIV infection. However, the sexual and reproductive health needs of many women extend beyond HIV prevention, and research is ongoing to develop multi-purpose prevention technologies (MPTs) that offer dual HIV and pregnancy protection. We do not yet know if these products will be an efficient use of constrained health resources. In this paper, we estimate the cost-effectiveness of combinations of candidate multi-purpose prevention technologies (MPTs), in South Africa among general population women and female sex workers (FSWs). METHODS: We combined a cost model with a static model of product impact based on incidence data in South Africa to estimate the cost-effectiveness of five candidate co-formulated or co-provided MPTs: oral PrEP, intravaginal ring, injectable ARV, microbicide gel and SILCS diaphragm used in concert with gel. We accounted for the preferences of end-users by predicting uptake using a discrete choice experiment (DCE). Product availability and protection were systematically varied in five potential rollout scenarios. The impact model estimated the number of infections averted through decreased incidence due to product use over one year. The comparator for each scenario was current levels of male condom use, while a health system perspective was used to estimate discounted lifetime treatment costs averted per HIV infection. Product benefit was estimated in disability-adjusted life years (DALYs) averted. Benefits from contraception were incorporated through adjusting the uptake of these products based on the DCE and through estimating the costs averted from avoiding unwanted pregnancies. We explore the additional impact of STI protection through increased uptake in a sensitivity analysis. RESULTS: At central incidence rates, all single- and multi-purpose scenarios modelled were cost-effective among FSWs and women aged 16-24, at a governmental willingness-to-pay threshold of $1175/DALY averted (range:$214-$810/DALY averted among non-dominant scenarios), however, none were cost-effective among women aged 25-49 (minimum$1706/DALY averted). The cost-effectiveness of products improved with additional protection from pregnancy. Estimates were sensitive to variation in incidence assumptions, but robust to other parameters. CONCLUSIONS: To the best of our knowledge, this is the first study to estimate the cost-effectiveness of a range of potential MPTs; suggesting that MPTs will be cost-effective among higher incidence FSWs or young women, but not among lower incidence older women. More work is needed to make attractive MPTs available to potential users who could use them effectively

Understanding user perspectives of and preferences for oral PrEP for HIV prevention in the context of intervention scale-up: a synthesis of evidence from sub-Saharan Africa.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) for HIV prevention has been proven to significantly reduce new HIV infections yet scale-up has been slow. As contexts continue to adjust to make space for PrEP, it is crucial to understand the perspectives and experiences of potential end-users. In order to inform PrEP and demand creation interventions, this paper examines personal perspectives on adopting and using PrEP among HIV at-risk populations in sub-Saharan Africa. METHODS: Using the principles of a scoping review in July 2018, we explored the extent, range, and nature of published literature regarding PrEP uptake and use among; men who have sex with men, HIV serodiscordant couples, adolescent girls and young women, pregnant and breastfeeding women, women partners of migrant workers; and people who use drugs. Steps included: identification of the research question; identification of relevant studies; study selection; charting the data; and collation - summarizing and reporting results. PubMed and PsycInfo were searched for papers relating to PrEP uptake and use in sub-Saharan Africa. Resulting papers were reviewed with data extracted and compiled in Excel for analysis. A broad content analysis was conducted and organized into high-level themes. RESULTS AND DISCUSSION: Thirty-five papers were included in this review. There was little opposition in general to oral PrEP; however, there were significant nuances in its broader acceptability, applicability, and usability. We identified five themes within which these are discussed. These relate to balancing complexities of personal empowerment and stigma; navigating complex risk environments; influences of relationships and partners; efficacy and side effects; and practicalities of use. This body of research suggests that while product attributes and the logistics of PrEP delivery and use are important topics, it is vital to consider stigma, the interactions of PrEP use with relationships, and the need for broader understanding of ARVs for prevention versus treatment. CONCLUSIONS: Planning for, programming and promoting the adoption of oral PrEP necessitates a deeper understanding of end-user priorities in order to ensure successful interventions. This review illustrates the nuances facilitating or deterring PrEP use that may affect the larger effort of PrEP scale-up

"I am still negative": Female sex workers' perspectives on uptake and use of daily pre-exposure prophylaxis for HIV prevention in South Africa.

Women remain highly vulnerable to HIV infection in sub-Saharan Africa, with female sex workers (FSWs) facing some of the highest rates of HIV. Oral pre-exposure prophylaxis (PrEP) has the potential to reduce new infections among populations at highest risk and end-user perspectives of actual use in 'real-world' settings are critical to informing PrEP implementation. This paper presents findings from serial in-depth interviews (IDIs) conducted with FSW participants during the course of the Treatment And Prevention for Sex workers (TAPS) Demonstration Project in South Africa, exploring the lived experiences and perceptions of taking up and using PrEP. This research provides insight into risks and responsibilities facing FSWs perceived as prominent drivers in taking up and using PrEP, how PrEP was adopted to mitigate risk or ameliorate realities, and the characteristics of PrEP most valued, all of which are critical to consider in scale-up. Overall, distrust in the existence and/or efficacy of PrEP affected the motivation of women to come to the clinic and to maintain use. As one of the first reports of PrEP use among FSWs outside of a clinical trial setting, this research shows that it will be important to ensure accurate, relevant, and widespread messaging in communities to generate demand and support for PrEP