Willingness to Use Long-Acting Injectable PrEP Among PrEP Naïve Black and Hispanic Sexual Gender Minority Persons.

In December 2021, long-acting injectable pre-exposure prophylaxis (LAI-PrEP) was approved for the prevention of HIV in at-risk adults and adolescents. LAI-PrEP may address adherence issues of daily oral daily PrEP and PrEP stigma. However, studies assessing LAI-PrEP willingness among PrEP naive Black and Hispanic sexual and gender minority (SGM) persons- a group disproportionately impacted by the HIV epidemic in the United States - is rare. To assess the extent of and characteristics of willingness to use LAI-PrEP in a national sample of Black and Hispanic SGM who are self-reported that they have never used PrEP. We analyzed data from a national sample of Black and Hispanic SGM collected between March and August 2020. We used log-binomial regression models to assess characteristics associated with willingness to use LAI-PrEP. Of the overall sample (N = 380), the mean age was 24 (SD = 2.8) and the majority of the sample (54%, n = 205) reported willingness to use LAI-PrEP. In multivariable log-binomial regression models, PrEP stigma was independently associated with less [prevalence ratio (PR) = 0.7, 95% confidence interval (CI) = 0.6, 0.9], while number of sexual partners in the past 12 months was associated with a more willingness to use LAI-PrEP (PR = 1.1, 95% CI = 1.0, 1.2). Our findings highlight the persistence of PrEP stigma as a potential barrier to willingness to use LAI-PrEP in this sample of Black and Hispanic SGM who have never used PrEP. Additional work needs to be done to reduce PrEP stigma more broadly.

Weighing the Options: Which PrEP (Pre-exposure Prophylaxis) Modality Attributes Influence Choice for Young Gay and Bisexual Men in the United States?

Pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission, but uptake and adherence among young men who have sex with men (YMSM) remains suboptimal. New PrEP formulations may enhance PrEP use, but little is known about their acceptability. We enrolled 39 cis- and transgender YMSM (age 18-34) from Boston, MA; Jackson, MS; Birmingham, AL; and New Orleans, LA, who participated in video-based focus groups (n = 30) or in-depth interviews (n = 9) to examine how new PrEP products (e.g., injections, monthly pills, implants) are perceived and might be improved for YMSM. Focus groups were transcribed, coded, and analyzed using grounded theory and content analysis. Nearly half (46%) of participants were Black; 11% identified as Hispanic. Seventy-nine percent were PrEP experienced. Product preference was driven by the desire for flexible, safe, effective, and affordable PrEP options. A majority of participants preferred subcutaneous injections every 6 months or monthly pills dispersed in 3 or 4 doses. Subcutaneous injections and batched monthly pills were favored by those with demanding schedules and those who desired fewer provider visits; monthly pills were more appealing for those who feared needles. Despite broad preferences for longer-acting products for convenience, participants raised concerns regarding side effects and waning protection after missed doses. Participants felt that more education about safety and efficacy profiles of new products could influence their attitudes. These findings suggest that it is important to prioritize YMSM's dynamic lifestyles during product development, and that product safety and efficacy information should be accessible in youth-friendly language.

Need for informed providers: exploring LA-PrEP access in focus groups with PrEP-indicated communities in Baltimore, Maryland.

BACKGROUND: The approval of long-acting pre-exposure prophylaxis PrEP (LA-PrEP) in the United States brings opportunities to overcome barriers of oral PrEP, particularly among sexual and gender minority communities who bear a higher HIV burden. Little is known about real-time decision-making among potential PrEP users of LA-PrEP post-licensure. METHODS: We held focus group discussions with people assigned male at birth who have sex with men in Baltimore, Maryland to explore decision-making, values, and priorities surrounding PrEP usage. A sexual and gender minority-affirming health center that provides PrEP services supported recruitment. Discussions included a pile-sorting activity and were audio-recorded. Recordings were transcribed and analyzed iteratively, combining an inductive and deductive approach. RESULTS: We held five focus groups from Jan-June 2023 with 23 participants (21 cisgender men who have sex with men, two transgender women who have sex with men; mean age 37). Among participants, 21 were on oral PrEP, one was on injectable PrEP, and one had never taken PrEP. Most had never heard about LA-PrEP. When making decisions about PrEP, participants particularly valued efficacy in preventing HIV, side effects, feeling a sense of security, and ease of use. Perceptions varied between whether oral or injectable PrEP was more convenient, but participants valued the new opportunity for a choice in modality. Factors influencing PrEP access included cost, individual awareness, provider awareness, and level of comfort in a healthcare environment. Participants emphasized how few providers are informed about PrEP, placing the burden of being informed about PrEP on them. Comfort and trust in a provider superseded proximity as considerations for if and where to access PrEP. CONCLUSIONS: There is still low awareness about LA-PrEP among sexual and gender minority communities; thus, healthcare providers have a critical role in influencing access to LA-PrEP. Despite this, providers are still vastly underinformed about PrEP and underprepared to support clients in contextualized ways. Clients are more likely to engage in care with affirming providers who offer non-judgmental conversations about sex and life experiences. Provider education in the United States is urgently needed to better support clients in choosing a PrEP modality that is right for them and supporting adherence for effective HIV prevention.

URCHOICE: Preferences for Pre-Exposure Prophylaxis (PrEP) Options for HIV Prevention Among Kenyan men who have sex with men and Transgender Women in Nairobi, Kisumu and the Coast.

HIV prevention method preferences were evaluated among Kenyan men who have sex with men (MSM) and transgender women (TW) from three sites: Kisumu, Nairobi and the Coast. Information sessions detailing the attributes, duration of protection, route of administration and probable visibility were attended by 464 HIV negative participants, of whom 423 (median age: 24 years) agreed to be interviewed. Across pairwise comparisons daily PrEP was by far the least preferred (1%); quarterly injections (26%) and monthly pills (23%) were most preferred, followed by yearly implant (19%) and condoms (12%). When participants were "forced" to choose their most preferred PrEP option, only 10 (2.4%) chose the daily pill; more (37.1%) chose the quarterly injection than the monthly pill (34.8%) and the yearly implant (25.8%). TW preferred the yearly implant over the quarterly injection. To achieve the rates of PrEP uptake and adherence necessary for protecting large proportions of vulnerable MSM and TW, a variety of long-acting products should be developed and made accessible to appeal to a diversity of preferences.

HIV prevention at drug shops: awareness and attitudes among shop dispensers and young women about oral pre-exposure prophylaxis and the dapivirine ring in Shinyanga, Tanzania.

BACKGROUND: HIV risk remains high among adolescent girls and young women (AGYW, ages 15-24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring. METHODS: In July-August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create "girl-friendly" drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3-5 months, we surveyed AGYW (n = 56) customers about their interest in oral PrEP and the ring. RESULTS: Among dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 29% of AGYW were married or had a steady partner and 18% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children. CONCLUSIONS: Despite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.

Understanding the Acceptability of Subdermal Implants as a Possible New HIV Prevention Method: Multi-Stage Mixed Methods Study.

BACKGROUND: A long-acting implant for HIV pre-exposure prophylaxis (PrEP) is in development in the Sustained Long-Action Prevention Against HIV (SLAP-HIV) trial. This could provide an alternative to oral PrEP. OBJECTIVE: Our mixed methods study aimed to understand (1) users' experiences with a similar subdermal implant for contraception and (2) factors influencing the likelihood that gay and bisexual men (GBM) would use a proposed PrEP implant. METHODS: Work was completed in 4 stages. In stage 1, we conducted a scientific literature review on existing subdermal implants, focusing on users' experiences with implant devices. In stage 2, we reviewed videos on YouTube, focusing on the experiences of current or former contraceptive implant users (as these implants are similar to those in development in SLAP-HIV). In stage 3, individuals who indicated use of a subdermal implant for contraception in the last 5 years were recruited via a web-based questionnaire. Eligible participants (n=12 individuals who liked implants a lot and n=12 individuals who disliked implants a lot) completed in-depth phone interviews (IDIs) about their experiences. In stage 4, results from IDIs were used to develop a web-based survey for HIV-negative GBM to rate their likelihood of using a PrEP implant on a scale (1=very unlikely and 5=very likely) based on likely device characteristics and implant concerns identified in the IDIs. RESULTS: In the scientific literature review (stage 1), concerns about contraceptive implants that could apply to the PrEP implants in development included potential side effects (eg, headache), anticipated high cost of the device, misconceptions about PrEP implants (eg, specific contraindications), and difficulty accessing PrEP implants. In the stage 2 YouTube review, individuals who had used contraceptive implants reported mild side effects related to their device. In stage 3, implant users reported that devices were comfortable, unintrusive, and presented only minor discomfort (eg, bruising) before or after insertion and removal. They mainly reported removing or disliking the device due to contraceptive-related side effects (eg, prolonged menstruation). Participants in the stage 4 quantitative survey (N=304) were mainly gay (204/238, 85.7%), white (125/238, 52.5%), cisgender men (231/238, 97.1%), and 42.0% (73/174) of them were on oral PrEP. Not having to take a daily pill increased the likelihood of using PrEP implants (mean 4.13). Requiring >1 device to achieve 1 year of protection (mean range 1.79-2.94) mildly discouraged PrEP implant use. Participants did not mind moderate bruising, a small scar, tenderness, or bleeding after insertion or removal, and an implant with a size slightly larger than a matchstick (mean ratings 3.18-3.69). CONCLUSIONS: PrEP implants are promising among GBM. Implant features and insertion or removal-related concerns do not seem to discourage potential users. To ensure acceptability, PrEP implants should require the fewest possible implants for the greatest protection duration.

Preparing for the Implementation of Long-Acting Injectable Cabotegravir for HIV Pre-Exposure Prophylaxis Within the Brazilian Public Health System (ImPrEP CAB Brasil): Qualitative Study.

BACKGROUND: Although long-acting, injectable cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention in clinical trials, research is needed to guide effective implementation in real-world settings. Formative work with community members and health care providers (HCPs) is important to provide insight into the needs and contexts of specific populations and reveal potential barriers and facilitators for implementation projects. OBJECTIVE: We aimed to describe the results from formative work to develop an implementation package for CAB-LA PrEP within the ImPrEP CAB Brasil study. METHODS: ImPrEP CAB Brasil is an implementation study of same-day delivery of CAB-LA PrEP for young sexual and gender minority (SGM) groups (aged 18-30 years) in 6 existing oral PrEP public health clinics. We conducted formative research to prepare for the implementation of ImPrEP CAB Brasil through community mobilization, process mapping with HCPs with experience in CAB-LA, and focus group discussions (FGDs) with young SGM groups (n=92) and HCPs (n=20) to identify initial perceptions of facilitators and barriers for CAB-LA PrEP implementation, refine the mobile health (mHealth) educational tool, and evaluate the acceptability of using a text message appointment reminder intervention through WhatsApp. FGDs were recorded, transcribed, systematically coded, and analyzed with thematic categorization by trained researchers using a qualitative data analysis program ATLAS.ti (version 7). RESULTS: A community mobilization team comprising 34 SGM community leaders collaborated in creating a prototype for an mHealth educational tool and contributed to the planning of peer education activities. We created 3 process maps for each site to describe the initial visit, follow-up visits, and laboratory flow. The main challenge identified for same-day CAB-LA PrEP delivery was the extended duration of clinic visits due to the numerous laboratory tests and HIV counseling steps required. Proposed solutions included having point-of-care HIV rapid tests instead of laboratory tests and additional counseling staff. Barriers for CAB-LA PrEP implementation identified through FGDs were the training of HCPs, support for adherence to injection appointments, and stigma or discrimination against SGM groups and persons using PrEP. The mHealth educational tool and WhatsApp reminders were highly acceptable by SGM groups and HCPs, indicating their potential to support PrEP choice and adherence. Content analysis on the cultural appropriateness of the language and overall clarity of the material contributed to the refinement of the mHealth tool. CONCLUSIONS: Structured formative work with SGM persons and HCPs generated important refinements to context-specific materials and plans to launch ImPrEP CAB Brasil in public health clinics. Ongoing implementation monitoring will use the process maps to identify additional barriers and potential solutions to same-day delivery of CAB-LA PrEP. Summative evaluations are needed to measure the effectiveness of the mHealth educational tool to support PrEP choice and the use of WhatsApp appointment reminders.

What does the scale-up of long-acting HIV pre-exposure prophylaxis mean for the global hepatitis B epidemic?

INTRODUCTION: The HIV and hepatitis B virus (HBV) epidemics are interconnected with shared routes of transmission and specific antiviral drugs that are effective against both viruses. Nearly, 300 million people around the world live with chronic HBV, many of whom are from priority populations who could benefit from HIV prevention services. Oral pre-exposure prophylaxis (PrEP) for HIV has implications in the prevention and treatment of HBV infection, but many people at increased risk of HIV acquisition may instead prefer long-acting formulations of PrEP, which are currently not active against HBV. DISCUSSION: People at increased risk for HIV acquisition may also be at risk for or already be living with HBV infection. Oral PrEP with tenofovir is effective in preventing both HIV and HBV, and tenofovir is also the recommended treatment for chronic HBV infection. Although implementation of oral PrEP has been challenging in sub-Saharan Africa, investments in its scale-up could secondarily reduce the clinical impact of HBV. Long-acting PrEP, including injectable medicines and implantable rings, may overcome some of the implementation challenges associated with oral PrEP, such as daily pill burden, adherence challenges and stigma; however, current formulations of long-acting PrEP do not have activity against HBV replication. Ideally, PrEP programmes would offer both oral and long-acting formulations with HBV screening to optimize HIV prevention services and HBV prevention and care, when appropriate. People who are not immune to HBV would benefit from being vaccinated against HBV before initiating long-acting PrEP. People who remain non-immune to HBV despite vaccination may benefit from being offered oral, tenofovir-based PrEP given its potential for HBV PrEP. People using PrEP and living with HBV who are not linked to dedicated HBV care would also benefit from laboratory monitoring at PrEP sites to ensure safety when using and after stopping tenofovir. PrEP programmes are ideal venues to offer HBV screening, HBV vaccination for people who are non-immune and treatment with tenofovir-based PrEP for people with indications for HBV therapy. CONCLUSIONS: Long-acting PrEP holds promise for reducing HIV incidence, but its implications for the HBV epidemic, particularly in sub-Saharan Africa, should not be overlooked.

The Perceived Added Value of Bimonthly Injectable Pre-Exposure Prophylaxis According to West African Men Who Have Sex with Men: A Focus Group Study.

Bimonthly long-acting injectable pre-exposure prophylaxis (LAI-PrEP) can become an important additional tool for HIV prevention among West African men who have sex with men (MSM). The objective was to explore the perceived added value of LAI-PrEP as an HIV prevention tool among MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. We conducted eight focus group discussions among 62 HIV-negative MSM between April and May 2021. Participants were recruited via local community-based clinics. Data collection and analysis were guided by grounded theory and community-based participatory approaches. Participants were generally knowledgeable about HIV, and explained particular barriers for HIV prevention in their communities (e.g., denial of HIV). The added value of LAI-PrEP relative to condoms was similar to oral pre-exposure prophylaxis (PrEP) in terms of perceived advantages (e.g., improved sexual satisfaction) or disadvantages (e.g., no protection against other sexually transmitted infections). Compared with oral PrEP, LAI-PrEP was perceived to provide better protection against HIV and to be more convenient (e.g., no need to be mindful of intake and less risk for stigma). Concerns included fear of needles, doubts about efficacy, potential side effects, and difficulties for ensuring timely injections (e.g., when traveling abroad). The results demonstrate that injectable PrEP can be of particular interest to subgroups of West African MSM, although existing HIV prevention tools such as condoms and oral PrEP will remain valuable alongside of, or instead of, LAI-PrEP. Increasing awareness about HIV and tackling discrimination based on sexual orientation continue to be crucial factors to be addressed for HIV prevention.

Promises and potential pitfalls of long-acting injectable pre-exposure prophylaxis.

The number of products that can provide pre-exposure prophylaxis (PrEP) for HIV prevention is expanding, with three now approved in South Africa (oral Tenofovir-based PrEP, injectable Cabotegravir, and a Dapivirine-based vaginal ring) and more in the development pipeline. Although highly effective and safe, oral PrEP products have not reduced HIV incidence in South Africa to the extent seen in other countries, primarily due to adherence challenges, rapidly diminishing persistence over time, and insufficient scale-up of PrEP service delivery. The Dapivirine vaginal ring, which provides 1-month-long protection, provides women with a new and discreet choice for PrEP; however, it is Cabotegravir long-acting (CAB LA) that is anticipated to land the largest impact. Administered as an intramuscular injection given every 2 months, CAB LA is safe, highly efficacious, and expected to become available in South Africa in late 2023. Yet, clinical and implementation questions remain, including the need to understand and characterise breakthrough HIV infections amongst CAB LA users, knowledge of how to package each PrEP product in a new context of PrEP choice, and how to avoid the remedicalisation of PrEP access following extensive efforts to make oral PrEP delivery differentiated and community based.

Interrogating the promise of long-acting HIV pre-exposure prophylaxis.

Oral HIV pre-exposure prophylaxis (PrEP) is a well-established product that provides a safe and highly effective way for individuals to protect themselves against HIV infection. However, hopes of a significant reduction in HIV incidence have been disappointing because of low uptake, adherence challenges to a daily pill regimen, and consistently high discontinuation rates within 6 months of initiation. Long-acting agents have been long awaited for their potential to facilitate adherence and to offer a choice between PrEP products. As the first long-acting agents enter the market, with more poised to follow, questions around how to integrate long-acting agents into oral PrEP platforms, and what the potential advantages and pitfalls of this integration will be, now need to be considered.

Estimating the impact of HIV PrEP regimens containing long-acting injectable cabotegravir or daily oral tenofovir disoproxil fumarate/emtricitabine among men who have sex with men in the United States: a mathematical modelling study for HPTN 083.

Background: The HPTN 083 trial demonstrated superiority of HIV pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB) to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) among men who have sex with men (MSM). We compared the potential population-level impact of TDF/FTC and CAB among MSM in Atlanta, Georgia. Methods: An MSM HIV transmission model was calibrated to Atlanta-specific data on HIV prevalence and PrEP usage (percentage of uninfected MSM on PrEP), assuming only PrEP-indicated MSM used PrEP. CAB effectiveness (efficacy × adherence) of 91% was estimated using data from HPTN 083 and previous TDF/FTC trials. We estimated HIV infections averted over 5/10 years if TDF/FTC use were maintained, or if all TDF/FTC users switched to CAB in January 2022 (vs. no PrEP or continued TDF/FTC use). CAB scenarios with 10%/20% more users were also considered. Progress towards Ending the HIV Epidemic (EHE) goals (75%/90% fewer HIV infections in 2025/2030 vs. 2017) was estimated. Findings: We predicted TDF/FTC at current usage (∼28%) would avert 36.3% of new HIV infections (95% credible interval 25.6-48.7%) among all Atlanta MSM over 2022-2026 vs. no PrEP. Switching to CAB with similar usage may prevent 44.6% (33.2-56.6%) infections vs. no PrEP and 11.9% (5.2-20.2%) infections vs. continued TDF/FTC. Increasing CAB usage 20% could increase the incremental impact over TDF/FTC to 30.0% over 2022-2026, getting ∼60% towards reaching EHE goals (47%/54% fewer infections in 2025/2030). Reaching the 2030 EHE goal would require 93% CAB usage. Interpretation: If CAB effectiveness were like HPTN 083, CAB could prevent more infections than TDF/FTC at similar usage. Increased CAB usage could contribute substantially towards reaching EHE goals, but the usage required to meet EHE goals is unrealistic. Funding: NIH, MRC.

HIV prevention: better choice for better coverage.

INTRODUCTION: Antiretroviral-based pre-exposure prophylaxis (PrEP) is today an established, effective and safe method of HIV prevention used in multiple countries worldwide by a broad range of populations at risk of HIV infection. Biomedical innovations are critical in supporting the primary prevention of HIV; however, their potential can only be maximized if end-user challenges are recognized, described and used to develop next-generation models. DISCUSSION: First-generation PrEP, a daily oral pill, is highly efficacious, discreet and affords users the ability to commence and conclude treatment rapidly. However, consistent daily adherence and persistence is challenging, especially among younger populations, due in part to side effects, the risk of stock-outs and a lack of pill storage options. Second-generation PrEP, longer acting agents that require less frequent dosing, could overcome such challenges. Agents that have shown efficacy in clinical trials include a monthly vaginal ring and PrEP injectables to be administered every 8 weeks, while products in development include 6 monthly injectables, oral therapy that uses monthly rather than daily pills, implants and the potential for long-acting passive immunization. CONCLUSIONS: Second-generation PrEP agents will have the potential to offer improved adherence and less frequent reminders once they have undergone further development and the delivery systems that will best support them have been established. In order to pursue global UNAIDS targets of reducing new HIV infections to fewer than 500,000 annually by 2025, and to ensure that all people have access to prevention options that meet their specific prevention needs, both early and next-generation PrEP options are needed.