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.

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.

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.

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.

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.

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.

When are declines in condom use while using PrEP a concern? Modelling insights from a Hillbrow, South Africa case study.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is a promising new prevention approach for those most at risk of HIV infection. However, there are concerns that behavioural disinhibition, specifically reductions in condom use, might limit PrEP's protective effect. This study uses the case of female sex workers (FSWs) in Johannesburg, South Africa, to assess whether decreased levels of condom use following the introduction of PrEP may limit HIV risk reduction. METHOD: We developed a static model of HIV risk and compared HIV-risk estimates before and after the introduction of PrEP to determine the maximum tolerated reductions in condom use with regular partners and clients for HIV risk not to change. The model incorporated the effects of increased STI exposure owing to decreased condom use. Noting that condom use with regular partners is generally low, we also estimated the change in condom use tolerated with clients only, to still achieve 50 and 90% risk reduction on PrEP. The model was parameterized using data from Hillbrow, Johannesburg. Sensitivity analyses were performed to ascertain the robustness of our results. RESULTS: Reductions in condom use could be tolerated by FSWs with lower baseline condom use (65%). For scenarios where 75% PrEP effectiveness is attained, 50% HIV-risk reduction on PrEP would be possible even with 100% reduction in condom use from consistent condom use as high as 70% with clients. Increased exposure to STIs through reductions in condom use had limited effect on the reductions in condom use tolerated for HIV risk not to increase on PrEP. CONCLUSIONS: PrEP is likely to be of benefit in reducing HIV risk, even if reductions in condom use do occur. Efforts to promote consistent condom use will be critical for FSWs with high initial levels of condom use, but with challenges in adhering to PrEP.

Planning for HIV preexposure prophylaxis introduction: lessons learned from contraception.

PURPOSE OF REVIEW: We summarize key lessons learned from contraceptive development and introduction, and implications for preexposure prophylaxis (PrEP). RECENT FINDINGS: New approaches to HIV prevention are urgently needed. PrEP is a new technology for HIV prevention. Uncertainty remains about its acceptance, use and potential to have an impact on the HIV epidemic. Despite imperfect use and implementation of programs, the use of modern contraception has led to significant reproductive health and social gains, making it one of the public health's major achievements. Guided by the WHO strategic approach to contraception introduction, we identified the following lessons for PrEP introduction from contraception: (1) the importance of a broader focus on the method mix rather than promotion of a single technology, (2) new technologies alone do not increase choice--service delivery systems and providers are equally important to success, and (3) that failure to account for user preferences and social context can undermine the potential of new methods to provide benefit. SUMMARY: Taking a strategic approach to PrEP introduction that includes a broader focus on the technology/user interface, the method mix, delivery strategies, and the context in which methods are introduced will benefit HIV prevention programs, and will ensure greater success.