Impact and cost-effectiveness of the national scale-up of HIV pre-exposure prophylaxis among female sex workers in South Africa: a modelling analysis.

INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.

From policy to practice: uptake of pre-exposure prophylaxis among adolescent girls and young women in United States President's Emergency Plan for AIDS Relief-supported countries, 2017-2020.

BACKGROUND: The US President's Emergency Plan for AIDS Relief's (PEPFAR) first implemented pre-exposure prophylaxis (PrEP) for HIV prevention through the Determined, Resilient, Empowered, AIDS-Free, Mentored and Safe (DREAMS) partnership in 2016. PrEP is a critical intervention to achieve the main objective of DREAMS, reducing new HIV infections among 15-14 year old adolescent girls and young women (AGYW) in 15 high HIV burdened countries. METHODS: We describe uptake of PrEP among AGYW in PEPFAR. Most PrEP programs screened persons who tested HIV-negative for eligibility and offered PrEP as part of combination prevention with follow-up, including repeat HIV testing and counseling, at 3-month intervals. Platforms providing comprehensive services for AGYW were also leveraged. We examined two PEPFAR monitoring indicators, using the FY20Q4 Monitoring, Evaluation, Reporting (MER) indicator dataset to assess progress in PrEP uptake, and descriptive narratives to understand successes and challenges from fiscal year 2017 to 2020. To assess coverage, we calculated the PrEP to Need ratio (PnR) using a published methodology. RESULTS: From FY2017 to FY2020, 576570 total clients initiated PrEP and the number of PEPFAR countries offering PrEP doubled from 12 to 24. Of 360073 (62% of total) initiations among women, 52% were among AGYW with steady increases from year to year. Among all AGYW, 20-24-year-old women represented a significantly higher proportion of PrEP initiators than adolescents (15-19years) (64 versus 36%, P  < 0.05). Of all 186985 PrEP initiations among AGYW, 99% were in DREAMS countries. Barriers, such as low demand and adherence, were addressed through outreach efforts, including mobile sites, use of technology to educate and support AGYW, media campaigns, and engaging peers in program implementation. We saw a 2.5-fold increase in PrEP uptake among AGYW from 2018 to 2019; by 2020, all DREAMS countries were implementing PrEP. However, PrEP coverage among AGYW in DREAMS countries remains low (PnR range: 0-4.1); only two have a PnR greater than 1 where there were more PrEP users than new HIV diagnoses. CONCLUSION: PrEP uptake among AGYW has grown since 2016; however, challenges remain. Tools to improve adherence are needed to improve PrEP persistence among AGYW. National policies to facilitate greater PrEP uptake among adolescents would be beneficial. A greater need for PrEP in DREAMS countries is evident and if realized, will contribute to epidemic control.

Pre-exposure prophylaxis (PrEP) uptake and service delivery adaptations during the first wave of the COVID-19 pandemic in 21 PEPFAR-funded countries.

BACKGROUND: Mitigation measures for the first wave of the COVID-19 pandemic and burden on health systems created challenges for pre-exposure prophylaxis (PrEP) service delivery. We examined PrEP uptake in PEPFAR programs before and after the start of the COVID-19 pandemic. METHODS: We studied two PEPFAR program monitoring indicators, using routine Monitoring, Evaluation, Reporting (MER) indicators capturing uptake of PrEP (PrEP_NEW) and overall use of PrEP (PrEP_CURR). We also analyzed descriptive program narratives to understand successes and challenges field teams encountered after the start of the COVID-19 pandemic. To assess changes in coverage of PrEP across 21 countries, we calculated the "PrEP to need ratio" (PnR) using a published methodology. We defined the pre-COVID time period as April 1, 2019 -March 31, 2020 and the COVID time period as April 1, 2020 -March 31, 2021. FINDINGS: The total number of persons who initiated PrEP increased by 157% from 233,250 in the pre-COVID-19 period compared with 599,935 in the COVID-19 period. All countries, except five, noted significant increases in PrEP uptake. PrEP uptake among adolescent girls and young women (AGYW) increased by 159% from 80,452 AGYW in the pre-COVID-19 period to 208,607 AGYW in the COVID-19 period. There were 77,430 key populations (KP) initiated on PrEP in the pre-COVID-19 period and 209,114 KP initiated in the COVID-19 period (a 170% increase). The PnR increased 214% in the COVID-19 period across all PEPFAR-supported countries. Adaptations, such as multi-month dispensing (MMD) of PrEP; virtual demand creation activities; decentralized, community-based and virtual service delivery, were implemented to maintain PrEP services. CONCLUSIONS: PEPFAR programs continued to maintain and initiate new clients on PrEP despite the challenges posed by the COVID-19 pandemic. Adaptations such as MMD of PrEP and use of technology were vital in expanding service delivery and increasing PrEP coverage. FUNDING: This project has been supported by the U.S. President's Emergency Plan for AIDS Relief.

The case for prevention - Primary HIV prevention in the era of universal test and treat: A mathematical modeling study.

Background: As antiretroviral therapy (ART) has scaled up and HIV incidence has declined, some have questioned the continued utility of HIV prevention. This study examines the role and cost-effectiveness of HIV prevention in the context of "universal test and treat" (UTT) in three sub-Saharan countries with generalized HIV epidemics. Methods: Scenarios were created in Spectrum/Goals models for Lesotho, Mozambique, and Uganda with various combinations of voluntary medical male circumcision (VMMC); pre-exposure prophylaxis; and a highly effective, durable, hypothetical vaccine layered onto three different ART scenarios. One ART scenario held coverage constant at 2008 levels to replicate prevention modeling studies that were conducted prior to UTT. One scenario assumed scale-up to the UNAIDS treatment goals of 90-90-90 by 2025 and 95-95-95 by 2030. An intermediate scenario held ART constant at 2019 coverage. HIV incidence was visualized over time, and cost per HIV infection averted was assessed over 5-, 15-, and 30-year time frames, with 3% annual discounting. Findings: Each prevention intervention reduced HIV incidence beyond what was achieved by ART scale-up alone to the 90-90-90/95-95-95 goals, with near-zero incidence achievable by combinations of interventions covering all segments of the population. Cost-effectiveness of HIV prevention may decrease as HIV incidence decreases, but one-time interventions like VMMC and a durable vaccine may remain cost-effective and even cost-saving as ART is scaled up. Interpretation: Primary HIV prevention is still needed in the era of UTT. Combination prevention is more impactful than a single, highly effective intervention. Broad population coverage of primary prevention, regardless of cost-effectiveness, will be required in generalized epidemic countries to eradicate HIV.

Preexposure Prophylaxis Among Pregnant and Lactating People in 18 PEPFAR-Supported Countries: A Review of HIV Strategies and Guidelines.

INTRODUCTION: Pregnant and lactating people (PLP) experience heightened risk of acquiring HIV, which adversely impacts their health and increases the risk for vertical HIV transmission. Preexposure prophylaxis (PrEP), as part of a combination prevention package, including condoms, sexually transmitted infection prevention, and regular HIV testing, is a safe, efficacious method to prevent HIV infections among PLP and their infants. This article examines the evolution of strategies and guidance on PrEP services for PLP from 18 countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: The 18 countries implement PEPFAR-supported prevention of vertical transmission of HIV and PrEP programs. We reviewed a total of 18 national HIV strategic plans, 28 national HIV guidelines, and 54 PEPFAR country operational plans (COPs) published in 2013-2020. We compared documents from 2013 to 2017 to those from 2017 to 2020 to assess for differences after the release of the 2017 World Health Organization recommendations supporting the use of PrEP by PLP at substantial risk of acquiring HIV. RESULTS: National HIV guidelines and PEPFAR COPs that endorsed PrEP for PLP through any categorization increased from 41% to 73% and 11% to 83%, respectively, in the pre-2017 and post-2017 periods. While many documents approved PrEP but not specifically for PLP (10 national strategic plans, 6 national guidelines, and 28 COPs), none of the documents explicitly prohibited PrEP for PLP. CONCLUSION: National HIV guidelines and PEPFAR COPs expanded inclusion of PLP in PrEP eligibility when comparing the pre-2017 and the post-2017 groups. However, policy gaps remain as only 36% (4/11) of the post-2017 national HIV guidelines included PLP as a specific priority population for PrEP. Inclusive national HIV strategic plans and guidelines on PrEP for PLP, together with effective program implementation, remain critical for reducing new infections in PLP and eliminating vertical transmission of HIV.

HIV PrEP is more than ART-lite: Longitudinal study of real-world PrEP services data identifies missing measures meaningful to HIV prevention programming.

INTRODUCTION: Evidence indicates HIV oral pre-exposure prophylaxis (PrEP) is highly efficacious and effective. Substantial early discontinuation rates are reported by many programs, which may be misconstrued as program failure. However, PrEP use may be non-continuous and still effective, since HIV risk fluctuates. Real-world PrEP use phenomena, like restarting and cyclical use, and the temporal characteristics of these use patterns are not well described. The objective of our study was to characterize and identify predictors of use patterns observed in large PrEP scale-up programs in Africa. METHODS: We analysed demographic and clinical data routinely collected during client visits between 2017 and 2019 in three Jhpiego-supported programs in Kenya, Lesotho and Tanzania. We characterized duration on/off PrEP and, using ordinal regression, modelled the likelihood of spending additional time off and identified factors associated with increasing cycle number. The Andersen-Gill model was used to identify predictors of time to PrEP discontinuation. To analyse factors associated with a client's first return following initiation, we used a two-step Heckman probit. RESULTS: Among 47,532 clients initiating PrEP, approximately half returned for follow-up. With each increase in cycle number, time off PrEP between use cycles decreased. The Heckman first-step model showed an increased probability of returning versus not by older age groups and among key and vulnerable population groups versus the general population; in the second-step model older age groups and key and vulnerable populations were less likely in Kenya, but more likely in Lesotho, to return on-time (refill) versus delayed (restarting). CONCLUSIONS: PrEP users frequently cycle on and off PrEP. Early discontinuation and delays in obtaining additional prescriptions were common, with broad predictive variability noted. Time off PrEP decreased with cycle number in all countries, suggesting normalization of use with experience. More nuanced measures of use are needed than exist for HIV treatment if effective use of PrEP is to be meaningfully measured. Providers should be equipped with measures and counselling messages that recognize non-continuous and cyclical use patterns so that clients are supported to align fluctuating risk and use, and can readily restart PrEP after stopping, in effect empowering them further to make their own prevention choices.

HIV prevention is not all about HIV - using a discrete choice experiment among women to model how the uptake and effectiveness of HIV prevention products may also rely on pregnancy and STI protection.

INTRODUCTION: In sub-Saharan Africa, considerable HIV-burden exists among women. Anti-retroviral (ARV) based prevention products could decrease this burden, and their uptake could be increased if they also protect against pregnancy and sexually transmitted infections (STI). METHODS: A discrete choice experiment (DCE) was undertaken in South Africa (2015) through a household survey of adult females (n = 158) and adolescent girls (n = 204) who self-reported HIV-negative status. The DCE was used to project the uptake (percentage using product) of oral pre-exposure prophylaxis (PrEP), vaginal rings, and injectable long-lasting ARV agents among these women, and how uptake could depend on whether these products protect against pregnancy or STI acquisition. Uptake estimates were used to model how each product could decrease a women's HIV acquisition risk. RESULTS: In adolescent women, there will be limited uptake (< 6% for any product) and impact (< 4% decrease in HIV acquisition risk) of new products unless they provide pregnancy protection, which could quadruple use and impact. Adult women have weaker preference for pregnancy protection, with moderate use (< 17% for each) and impact (< 14 percentage point decrease) if they only provide HIV protection. All women had highest preference for injectable ARVs, with oral PrEP having high preference if injectable ARVs are not available. Adult women will use the ring, but adolescent women will not. Importantly, even with three additional prevention products, all providing pregnancy and STI protection, > 14% of women will remain unprotected and > 31% of the baseline acquisition risk will remain. CONCLUSIONS: Incorporating multiple prevention components into new ARV-based prevention products may increase their uptake and impact among women.

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.

Determinants of heterosexual men's demand for long-acting injectable pre-exposure prophylaxis (PrEP) for HIV in urban South Africa.

BACKGROUND: Heterosexual men in South Africa are a large key population to exposure to HIV, yet preferences for HIV pre-exposure prophylaxis (PrEP) among this population have not, to date, been investigated in the literature. This paper aims to explore HIV prevention preferences among heterosexual men in urban South Africa, as well as to examine the demand and characteristics of men who favour long-acting injectable (LAI) PrEP over condoms and oral PrEP. METHODS: Data were collected among 178 self-reported HIV-negative heterosexual men, who were given example products and information before being asked which they preferred. Multivariate logistic regression was used to analyse which characteristics were associated with product choice. RESULTS: 48% (n = 85) of participants preferred LAI PrEP, while 33% (n = 58) and 20% (n = 35) chose oral PrEP and condoms respectively. Having children (marginal effect = 0.22; 95% CI [0.01, 0.44]) or having higher risk attitude scores (marginal effect = 0.03; 95% CI [0.01, 0.06]) was significantly associated with a choice of LAI PrEP, while those who had unprotected anal intercourse (marginal effect = - 0.42; 95% CI [- 0.57, - 0.27]) and those who were concerned with protection against other sexually transmitted infections over HIV (marginal effect = - 0.42; 95% CI [- 0.60, - 0.24]) appeared less likely to prefer LAI PrEP. CONCLUSIONS: The results suggested a relatively high demand and theoretical acceptability for LAI PrEP among heterosexual men in urban South Africa, but there appeared to be fewer distinct predictors for the willingness to use LAI PrEP compared to studies conducted among gay and bisexual men and women. Nevertheless, the findings contribute to the mapping of the demand and determinants of heterosexual men's preferences for novel antiretroviral-based prevention in sub-Saharan Africa, and the data could aid in the differentiated design of future HIV prevention strategies using LAI PrEP in conjunction with other methods.

"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.

Community Inclusion in PrEP Demonstration Projects: Lessons for Scaling Up.

Pre-exposure prophylaxis (PrEP) has emerged as a new HIV prevention strategy. A series of demonstration projects were conducted to explore the use of PrEP outside of clinical trial settings. Learning from the failures in community consultation and involvement in early oral tenofovir trials, these PrEP projects attempted to better engage communities and create spaces for community involvement in the planning and roll out of these projects. We briefly describe the community engagement strategies employed by seven Bill & Melinda Gates Foundation-funded PrEP demonstration projects and the lessons these projects offer for community engagement in PrEP implementation.

The effect of HIV prevention products on incentives to supply condomless commercial sex among female sex workers in South Africa.

Evidence suggests that economic factors play an important role in commercial sex work, in particular that condomless sex commands a price premium relative to condom-protected sex. This paper explores whether the use of a new HIV prevention product, with 100% efficacy but modeled after pre-exposure prophylaxis (PrEP), could change the price and quantity of condomless commercial sex supplied. We collected stated preference data from 122 HIV-negative female sex workers in urban South Africa, using a repeated choice experiment to simulate the impact of using PrEP on choices. Results suggest that the price premium for condomless sex would decrease by 73% with PrEP use and the quantity of condomless sex is predicted to increase by a factor of 2.27. Act price does not significantly affect choices without protection but strongly influences choices under full HIV protection. The utility offered by condoms reduces by around 15% under PrEP use. Because new HIV prevention products do not protect against other STIs or pregnancy, the unintended consequences of introducing HIV prevention products should be closely monitored, whereas users should not face stigma or blame for reacting rationally to exogenous changes to market conditions.

Risk perception and the influence on uptake and use of biomedical prevention interventions for HIV in sub-Saharan Africa: A systematic literature review.

BACKGROUND: Risk perception has been found to be a crucial factor explaining inconsistent or non-use of HIV prevention interventions. Considerations of risk need to expand beyond risk of infection to also include the personal, social, emotional, and economic risks associated with prevention intervention use. OBJECTIVES: This systematic review of qualitative peer-reviewed literature from sub-Saharan Africa examines perceptions of risk associated with HIV infection and HIV prevention intervention use. DATA SOURCES: We searched Medline, Embase, PsychInfo, Africa Wide Info, CINAHL, and Global Health for publications and screened them for relevance. STUDY ELIGIBILITY CRITERIA: Peer-reviewed qualitative studies published since 2003 were eligible for inclusion if they examined risk perception or uncertainty in the context of a medically regulated intervention. Only studies focusing on adults were included. STUDY APPRAISAL AND SYNTHESIS METHODS: Included publications were quality assessed using the Hawker method and coded thematically. RESULTS: 10318 unique papers were identified, of which 29 are included. Among the themes identified, a particularly salient one was the potential of HIV prevention interventions to threaten the stability of a relationship and impact on how and when people may-or may not-choose to use prevention interventions. LIMITATIONS: This literature review excludes grey-literature, which may have distinct valuable insights. We also excluded quantitative studies that may have challenged or triangulated our findings. CONCLUSIONS AND IMPLICATIONS: When considering the risk of HIV acquisition, it is insufficient to examine biological risk in isolation from the personal, relational and economic costs associated with intervention use. This loss of emotional, physical, or material support may be perceived as more consequential than the prevention of a potential infection.

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.

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.

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.

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.

Divergent Preferences for HIV Prevention: A Discrete Choice Experiment for Multipurpose HIV Prevention Products in South Africa.

BACKGROUND: The development of antiretroviral (ARV)-based prevention products has the potential to substantially change the HIV prevention landscape; yet, little is known about how appealing these products will be outside of clinical trials, as compared with the existing options. METHODS: We conducted a discrete choice experiment (DCE) to measure preferences for 5 new products among 4 important populations in the HIV response: adult men and women in the general population (aged 18 to 49 y), adolescent girls (aged 16 to 17 y), and self-identifying female sex workers (aged 18 to 49 y). We interviewed 661 self-reported HIV-negative participants in peri-urban South Africa, who were asked to choose between 3 unique, hypothetical products over 10 choice sets. Data were analyzed using multinomial, latent class and mixed multinomial logit models. RESULTS: HIV protection was the most important attribute to respondents; however, results indicate significant demand among all groups for multipurpose prevention products that offer protection from HIV infection, other STIs, and unwanted pregnancy. All groups demonstrated a strong preference for long-lasting injectable products. There was substantial heterogeneity in preferences within and across population groups. LIMITATIONS: Hypothetical DCE data may not mirror real-world choices, and products will have more attributes in reality than represented in choice tasks. Background data on participants, including sensitive areas of HIV status and condom use, was self-reported. CONCLUSIONS: These results suggest that stimulating demand for new HIV prevention products may require a more a nuanced approach than simply developing highly effective products. No single product is likely to be equally attractive or acceptable across different groups. This study strengthens the call for effective and attractive multipurpose prevention products to be deployed as part of a comprehensive combination prevention strategy.

Motivations and barriers to uptake and use of female-initiated, biomedical HIV prevention products in sub-Saharan Africa: an adapted meta-ethnography.

BACKGROUND: Women bear a disproportionate burden of HIV throughout the world prompting extensive research into HIV prevention products for women which has met with varied success. With an aim of informing future policy and programming, this review examines the barriers and motivations to the uptake and use of female initiated products in sub-Saharan countries. METHODS: We conducted a systematic review as an adapted meta-ethnography of qualitative data focused on actual use of products. After deduplication, 10,581 and 3861 papers in the first and second round respectively were screened. Following the PRISMA guidance, 22 papers were selected and synthesized using Malpass's definitions of first, second, and third order constructs. First order constructs, consisting of participant data published in the selected papers, were extracted and categorised by second and third order constructs for analysis. A weight of evidence review was conducted to compare and assess quality across the papers. RESULTS: The 22 papers selected span 11 studies in 13 countries. We derived 23 s order constructs that were translated into seven overarching third order constructs: Sexual Satisfaction, Trust, Empowerment and Control, Personal Well-being, Product use in the social-cultural environment, Practical Considerations, Risk Reduction, and Perceptions of Efficacy. Relationships and trust were seen to be as or more important for product use as efficacy. These constructs reveal an inherent inter-relationality where decision making around HIV prevention uptake and use cannot be binary or mono-faceted, but rather conducted on multiple levels. We developed a framework illustrating the central and proximal natures of constructs as they relate to the decision-making process surrounding the use of prevention products. CONCLUSIONS: Health systems, structural, and individual level HIV prevention interventions for women should adopt a holistic approach. Interventions should attend to the ways in which HIV prevention products can serve to reduce the likelihood of HIV transmission, as well as help to protect partnerships, enhance sexual pleasure, and take into account woman's roles in the social environment. Stigma, as well as sexuality, is likely to continue to influence product uptake and use and should be prominently taken into account in large-scale interventions. TRIAL REGISTRATION: Not applicable.