Oral Pre-exposure Prophylaxis Research Articles

Qualitative exploration of the barriers and facilitators to community pharmacy PrEP delivery for UK pharmacists and underserved community members using the COM-B model of behaviour change

ObjectivesExpanding delivery of oral pre-exposure prophylaxis (PrEP) to community pharmacies could improve access, aligning well with the UK government’s goals to eliminate new HIV acquisitions by 2030. Using the Capability,...

Preferences for Starting Daily, On-Demand, and Long-Acting Injectable HIV Preexposure Prophylaxis Among Men Who Have Sex With Men in the United States (2021-2022): Nationwide Online Cross-Sectional Study.

Long-acting (LA) injectable preexposureprophylaxis (PrEP) and on-demand PrEP may improve overall PrEP uptake among men who have sex with men (MSM), but little is understood about the PrEP option preferences of MSM in practical scenarios where they may choose between various PrEP options. This study aims to examine the preferences for starting various PrEP options among a US nationwide online convenience sample of MSM from September 2021 to February 2022. Participants reporting no prior HIV diagnosis were provided brief descriptions of each PrEP option and were asked, "If [PrEP option] were available from your local doctor and you could access it for free, would you go to your doctor in the next month to start [PrEP option]?" Those who said "yes" to multiple options were asked to rank them in order of preference. MSM currently taking daily oral (DO) PrEP were asked whether they would switch to on-demand or LA PrEP options. Log binomial models were created to examine the association between willingness to start or switch to on-demand and LA PrEP with various sociodemographic and behavioral factors. In the analytic sample (N=7760), among the participants who did not use any PrEP in the past 12 months (n=5108, 66%), 54% (n=2445) reported willingness to start at least 1 PrEP option and 41% (n=1845) of participants showed interest in starting multiple PrEP options. Overall, the highest willingness was reported for on-demand PrEP (n=2235, 44%), followed by DO PrEP (n=2174, 43%) and LA PrEP (n=1482, 29%). LA PrEP was ranked first among those interested in multiple options. Characteristics associated with ranking LA PrEP as a first option to start PrEP versus DO or on-demand PrEP were region of residence (residing in the West vs Northeast), report of sexually transmitted infection diagnosis in the past year, report of illicit drug use other than marijuana in the past year, and prior awareness of LA PrEP. Among current DO PrEP users (n=2379, 31%), 58% (n=1386) were willing to switch to on-demand or LA PrEP, and LA PrEP was ranked first among participants who were open to switching to both options. Willingness to switch to LA PrEP was higher among those who used illicit drugs other than marijuana in the past year, who heard of LA PrEP prior to the survey, and those who took 15 or less doses of oral PrEP in the last 30 days. LA PrEP was the highest-ranked option among most MSM who were willing to try multiple options or switch from DO PrEP. These findings highlight that LA PrEP might fill coverage gaps among MSM who use illicit drugs, have had a recent sexually transmitted infection diagnosis, and have less than optimal DO PrEP adherence.

HIV pre-exposure prophylaxis programmatic preferences among people who inject drugs: findings from a discrete choice experiment.

Pre-exposure prophylaxis (PrEP) holds promise for decreasing new HIV infections among people who inject drugs (PWID), yet daily oral PrEP use is low, and PrEP modality and delivery strategy preferences in this population remain understudied. From May 2022-June 2023, we conducted a discrete choice experiment (DCE) with PWID in San Diego, California. Participants viewed 18 PrEP program scenarios in sets of three and chose their preferred scenario within each set. Scenarios consisted of various combinations of five characteristics: PrEP modality (injectable, implantable, oral), frequency of use (annual, bi-monthly, daily), service location (community-based organization, clinic, telemedicine), prescription access location (on-site, street outreach, mail), and adherence supports (social support, outreach worker, phone/text reminder). Multinomial logit regression estimated probabilities of choosing PrEP program scenarios as a function of the five characteristics to estimate part-worth utility scores (PWUS; reflecting relative preferences for specific characteristic values) and relative importance scores (RIS; reflecting the relative influence of each characteristic on program choice). We also explored differences by hypothesized modifiers of preferences (i.e., sex assigned at birth, housing status, injection frequency, prior PrEP awareness). Among 262 participants, mean age was 43.1 years, and most reported male sex assigned at birth (69.5%), identified as non-Hispanic (60.3%), and were previously unaware of PrEP (75.2%). Frequency of use (RIS: 51.5) and PrEP modality (RIS: 35.3) had the greatest influence on PrEP program choice. Within these characteristics, participants had relative preferences for annual use (PWUS: 0.83) and oral PrEP (PWUS: 0.57), and relative aversions to daily use (PWUS: -0.76) and implantable PrEP (PWUS: -0.53). Generally, participants did not indicate preferences for specific service or prescription access locations, or adherence supports; however, among those with prior PrEP awareness, prescription access location and adherence supports had a slightly greater influence on PrEP program choices. Our study considered diverse PrEP scenarios and highlighted potential preferences for long-acting oral modalities. Although not currently available, renewed investment in long-acting oral PrEP formulations may facilitate PrEP care engagement among PWID. Additional delivery and implementation strategy research is needed to support PrEP uptake and persistence in this population.

Enhancing daily oral PrEP adherence with digital communications: Protocol for a systematic review and meta-analysis.

Pre-exposure prophylaxis (PrEP) stands as an effective tool in preventing HIV transmission among individuals at risk of HIV infection. However, the effectiveness of daily oral PrEP is contingent on the adherence of its users, which can pose a challenge for many individuals. Various studies have explored different interventions aimed at bolstering PrEP adherence. One recurring type of intervention revolves around digital communication (e.g., SMS, mobile applications) to send reminders for PrEP usage. The objective of our systematic review and meta-analysis is to address the following research question: What is the effectiveness of digital communication interventions in enhancing daily oral PrEP adherence among individuals at a heightened risk of HIV infection? This paper presents our study protocol. We will conduct searches across four health-related databases: Embase, PubMed, Web of Science, and PsycINFO. We will also explore other sources, including clinical trials registries and grey literature. Our search will be restricted to original randomized controlled trials published in English, French, and Spanish conducted since 2012, when PrEP was approved, to today. To ensure rigor, three reviewers will perform the systematic review and meta-analysis. This systematic review will adhere to the guidelines outlined in the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Our primary outcome of interest is proper daily oral PrEP adherence, which we will measure using association metrics (e.g., odds ratios). This review will offer insights into the effectiveness of utilizing digital communication methods to assist individuals at risk of HIV in improving their PrEP adherence. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42023471269.

Pre-Exposure Prophylaxis for the Prevention of HIV-1: An Assessment of Oral Pre-Exposure Prophylaxis Usage Patterns, First Evidence of HIV-1, and HIV-1 Risk Factors in the United States.

In clinical trials, once-daily oral tenofovir-based pre-exposure prophylaxis (PrEP) significantly reduced HIV-1 acquisition risk; however, this was highly dependent on medication adherence and persistence. We report clinical characteristics, PrEP usage patterns, first evidence of HIV-1, and associated risk factors among adults with commercial insurance using oral PrEP in the United States using health plan claims from the IQVIA PharMetrics® Plus database between January 1, 2015, and March 31, 2020, from individuals who newly initiated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or FTC/tenofovir alafenamide (TAF) for daily PrEP. Overall, 25,419 individuals were included (FTC/TDF, n = 24,232; FTC/TAF, n = 1187), with generally similar characteristics reported during the 6-month baseline period across cohorts. Mean follow-up length was 504 and 77 days for FTC/TDF and FTC/TAF, respectively, corresponding with the 2019 approval of FTC/TAF for PrEP. Similarly, mean PrEP use duration was 354 and 68 days for FTC/TDF and FTC/TAF, respectively. PrEP breaks (>90-day gap) were observed in 11.1% of individuals using FTC/TDF, with a mean break duration of 249 days; 20.0% of individuals using FTC/TDF and 7.3% using FTC/TAF had ≥1 sexually transmitted infection diagnosis during follow-up. From 6 to 12 months of follow-up, mean FTC/TDF proportion of days covered (PDC; 0.74 vs. 0.67) and persistence (70.2% vs. 57.4%) decreased; real-world PDC and persistence were lower than reported in globally conducted clinical trials. First evidence of HIV-1 was infrequent among individuals using FTC/TDF (0.6%), though 60.3% had PrEP on hand when HIV-1 definition was met; high-risk sexual behavior, syphilis, and gonorrhea were the most important risk factors.

Gene expression of tight junctions in foreskin is not affected by HIV pre-exposure prophylaxis

IntroductionTight junctions (TJs) serve as permeability filters between the internal and external cellular environment. A large number of proteins have been identified to be localized at the TJs. Due to limitations in tissue collection, TJs in the male genital tract have been understudied.MethodsWe analysed the transcriptomics of 132 TJ genes in foreskin tissue of men requesting voluntary medical male circumcision (VMMC) and enrolled in the Combined HIV Adolescent Prevention Study (CHAPS) trial conducted in South Africa and Uganda (NCT03986970). The trial evaluated the dose requirements for event-driven HIV pre-exposure prophylaxis (PrEP) with emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during insertive sex. A total of 144 participants were randomized to either control arm or one of 8 PrEP arms (n=16/arm), receiving oral FTC-TDF or FTC-TAF over one or two days. Following in vivo oral PrEP dosing and VMMC, the expression level of three important TJ proteins (CLDN-1, OCN and ZO-1) was measured ex vivo in foreskin tissue by Western blot. The expression of cytokine genes implicated in TJ regulation was determined. Non-parametric Kruskal-Wallis tests were used to compare TJ gene expression and protein levels by type of PrEP received, and Spearman’s correlation coefficients were calculated to assess whether TJ gene expression levels were related to cytokine gene levels or to PrEP drug concentrations and their active intracellularly phosphorylated metabolites.ResultsA high level of expression in foreskin tissue was found for 118 (of 132) TJ genes analysed; this finding contributed to create a map of TJ components within the male genital tract. Importantly, PrEP regimens tested in the CHAPS trial did not affect the expression of TJ genes and the analysed proteins in the foreskin; thus, further supporting the safety of this prevention strategy against HIV-1 transmission during insertive sex. Additionally, we identified the level of several cytokines’ genes to be correlated to TJ gene expression: among them, IL-18, IL-33 and VEGF.DiscussionTJs can limit viral entry into target cells; to affect this biological function viruses can reduce the expression of TJ proteins. Our study, on the expression and regulation of TJs in the foreskin, contribute important knowledge for PrEP safety and further design of HIV-1 prophylaxis.

Therapeutic drug monitoring of tenofovir disoproxil and emtricitabine in oral HIV pre-exposure prophylaxis (PrEP) users who have undergone gastrointestinal surgery.

Oral HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, but its efficacy depends on adequate absorption of drug, which may decrease following gastrointestinal surgery. Clinicians across eight Genito-urinary Medicine clinics in the United Kingdom submitted data on PrEP users with history of gastrointestinal surgery who were referred to a national complex PrEP multi-disciplinary team between June 2021 and April 2023. Anonymised data were submitted on demographics, surgical history, PrEP regimen, and results of therapeutic drug monitoring (TDM) and HIV screening tests. Descriptive analyses were performed in SPSS version 29. Nine cases described cis-gender men-who-have-sex-with-men (MSM) with median age of 47.4 years (IQR = 43 - 56.5) taking tenofovir disoproxil (TDF)/emtricitabine (FTC) daily (n = 8) or event-based (n = 1) as PrEP. Median time between PrEP initiation and TDM was 53 days (IQR = 8.5-1705). The mean (±SD) trough concentration of tenofovir (TFV) and FTC were 90.2 ± 27.7ng/mL and 76.0 ± 45.9ng/mL, respectively. All patients had a negative HIV test at follow-up. Plasma trough concentrations of TFV observed in our cohort taking TDF/FTC were above the expected concentrations associated with PrEP efficacy as previously described in the literature, suggesting that PrEP can be safely given in this population, with TDM used for reassurance.

Initiation and continued use of oral pre-exposure prophylaxis among pregnant and postpartum women in South Africa (PrEP-PP): a demonstration cohort study

When used effectively, oral pre-exposure prophylaxis (PrEP; tenofovir disoproxil fumarate and emtricitabine) prevents maternal HIV acquisition and reduces the risk of vertical transmission. Our study aimed to better understand PrEP initiation, continued use, and adherence in pregnant and postpartum women. The PrEP in Pregnancy and Postpartum (PrEP-PP) study is a demonstration cohort study that enrolled pregnant women aged 16 years and older without HIV attending their first antenatal care visit in Cape Town, South Africa, between Aug 29, 2019, and Oct 10, 2021. Eligible, consenting women were followed up quarterly up to 12 months postpartum with regular HIV testing and offer of PrEP with ongoing adherence counselling. The primary outcome was distribution of women across the PrEP cascade (ie, initiation and continuation up to 12 months postpartum) with crude and adjusted hazard ratios (HRs). We also report on HIV incidence by pregnancy and postpartum status. Overall, 1195 pregnant women were recruited and followed up (median age 26 years, IQR 23-31; median gestational age 21 weeks, IQR 15-31); 1009 (84·4%) started PrEP at enrolment. Among women who initiated PrEP at enrolment, 668 (67·5%) of 990 continued PrEP at the 1-month follow-up, 485 (49·9%) of 972 continued at 3 months, 392 (39·4%) of 994 at 6 months, and 275 (27·4%) of 1005 at 12 months. Of 186 women who did not accept PrEP at enrolment, 70 (37·6%) of 186 subsequently initiated PrEP. Overall, 200 (18·6%) of 1076 women continued PrEP at 12 months postpartum. Of 186 women who did not initiate PrEP at baseline, 70 (37·6%) subsequently initiated PrEP during the study. Factors associated with PrEP discontinuation up to 12 months postpartum included being married or cohabiting (adjusted HR 1·32, 95% CI 1·16-1·50), condomless sex since last visit (1·43, 1·23-1·65), reporting intimate partner violence (2·03, 1·59-2·59), or depression in the past 12 months (1·53, 1·14-2·05). Overall, 16 women seroconverted over 1673·8 woman-years (HIV incidence rate 0·96 per 100 woman-years, 95% CI 0·49-1·42); 14 discontinued PrEP use and two never initiated PrEP. HIV incidence was 0·28 per 100 woman-years during pregnancy (95% CI 0·22-0·33), and the incidence rate ratio was 1·77 per 100 woman-years (0·53-5·90) 0-6 months postpartum and 2·19 per 100 woman-years (0·61-7·83) 6-12 months postpartum compared with pregnant women. There is an urgent need for the integration of PrEP into antenatal and postnatal care and interventions that address barriers to continued use, including targeted counselling during pregnancy and postpartum to reduce PrEP discontinuation. National Institute of Mental Health and Fogarty International, US National Institutes of Health. For the French translation of the abstract see Supplementary Materials section.

Hoping to Adhere? Examining the Relationship Between Hope and Pre-exposure Prophylaxis Willingness, Adherence, and Persistence Among Young Women in South Africa and Zimbabwe (HPTN 082).

Hope is a powerful psychological construct which is linked to positive health. Greater hope is associated with improved antiretroviral therapy adherence; however, less is known about the impact of hope on oral pre-exposure prophylaxis (PrEP) outcomes. HIV Prevention Trials Network 082, was an open-label PrEP study among young women (ages 16-25) in South Africa and Zimbabwe. Hope was measured at baseline and follow-up using a subset of the Hope for the Future Scale (score range 6-24) and PrEP willingness was measured using a subscale of the HIV Prevention Readiness Measure (score range 6-30). Intracellular tenofovir-diphosphate (TFV-DP) concentrations were obtained from dried blood spot samples at weeks 13, 26, and 52; high PrEP adherence was defined as TFV-DP concentrations ≥ 700 fmol/punch. Persistence was defined as TFV-DP > 16 fmol/punch at weeks 26 and 52. Linear regression and generalized estimating equations were used to assess the relationship between hope and PrEP willingness, adherence, and persistence. The median age of participants (n = 432) was 21years (interquartile range [IQR]: 19-22). The mean hope score at baseline was 21.0 (SD = 3.4). Although hope was positively associated with PrEP willingness (β = 0.22, 95% CI 0.15, 0.37), it was not associated with high PrEP adherence (aRR = 1.00, 95% CI 0.96, 1.05), or persistence at follow-up (aRR = 1.02, 95% CI 0.99, 1.05). While cultivating hope may be an important strategy in building willingness to take oral PrEP, it may not be enough to sustain PrEP adherence or persistence.

Acceptability of six-monthly PrEP dispensing supported with interim HIV self-testing to simplify PrEP delivery in Kenya: findings from qualitative research

BackgroundIn Africa, dispensing oral HIV pre-exposure prophylaxis (PrEP) within already strained public health facilities has led to prolonged waiting periods and suboptimal experiences for clients. We sought to explore the acceptability of dispensing PrEP semiannually with interim HIV self-testing (HIVST) versus quarterly PrEP dispensing with clinic-based HIV testing to optimize clinic-delivered PrEP services.MethodsWe conducted a qualitative study within a non-inferiority individual-level randomized controlled trial testing the effect of six-monthly PrEP dispensing with HIVST compared to the standard-of-care three-monthly PrEP dispensing on PrEP clinical outcomes in Kenya (ClinicalTrials.gov: NCT03593629). Eligible participants were ≥ 18 years, refilling PrEP for the first time, and either in an HIV serodifferent relationship (men and women) or singly enrolled (women only). A subset of participants in the intervention group completed serial in-depth interviews (IDIs) at enrollment, six months, and 12 months. We utilized stratified purposive sampling to ensure representation across participant groups. We analyzed our qualitative data thematically using a combination of inductive and deductive approaches, the latter guided by the Theoretical Framework of Acceptability (TFA).ResultsBetween May 2018 and June 2021, we conducted 120 serial IDIs with 55 participants; 64% (35/55) were in a serodifferent relationship, 64% (35/55) were women, and the median age was 32 years (IQR 27–40). Overall, participants found this novel PrEP delivery model highly acceptable; it was well-liked, private (TFA construct: affective attitude), and less burdensome (TFA construct: burden) compared to standard PrEP delivery. Additionally, participants were confident in their ability to participate in the intervention (TFA construct: self-efficacy). Some participants, however, highlighted model disadvantages, including fewer opportunities for in-person counseling and potentially less accurate HIV testing (TFA construct: opportunity costs). Ultimately, most participants reported that the intervention allowed them to achieve their HIV prevention goals (TFA construct: perceived effectiveness) and that their confidence in at-home HIVST and PrEP continuation increased following each semiannual clinic visit.ConclusionsSemiannual PrEP clinic visits supported with six-monthly drug dispensing and interim HIVST was acceptable among PrEP users who experienced the intervention in Kenya. More comprehensive pre-intervention counseling and training on HIVST may help alleviate the client concerns presented, which were often resolved over time with intervention experience.

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.

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. We aimed to describe the results from formative work to develop an implementation package for CAB-LA PrEP within the ImPrEP CAB Brasil study. 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). 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. 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.

Trends in Oral and Injectable HIV Preexposure Prophylaxis Prescriptions in the US, 2013-2023

This study examines the prescribing trends of 3 oral preexposure prophylaxis medications and a long-acting injectable option from 2013 to 2023.

A Review and Economic Analysis of the Dapivirine Vaginal Ring as HIV Pre-Exposure Prophylaxis for Women, to Inform South African Public-Sector Guidelines.

South Africa has a high HIV incidence and oral pre-exposure prophylaxis (PrEP) is available as public-sector standard of care. Access to alternative prevention methods for women may further reduce HIV acquisition. South African public sector. We performed a systematic search for high-quality up-to-date guidelines recommending dapivirine rings as PrEP using the Grading of Recommendations Assessment, Development, and Evaluation -Adolopment process. We appraised the systematic review and randomized controlled trial (RCT) evidence underpinning the selected guideline's recommendations and conducted a cost-effectiveness analysis. The Grading of Recommendations Assessment, Development, and Evaluation evidence-to-decision framework guided the adaptation of source guideline recommendations, according to our local context. We identified the 2021 World Health Organization PrEP Guidelines, informed by 2 placebo-controlled RCTs, which were included in a contemporaneous systematic review. There were 23 fewer HIV acquisitions per 1000 clients with dapivirine ring vs placebo (95% confidence interval: 10 to 34), with no increase in adverse events (moderate certainty evidence). We found no RCTs comparing dapivirine to oral PrEP or among adolescent/pregnant/breastfeeding clients. Dapivirine is less cost-effective than oral PrEP at $14.59/ring, at the current price. The source guideline recommendation was adapted for the local context. Dapivirine ring seems to be less efficacious than oral PrEP, although comparative studies are lacking. Data on adolescents and pregnancy are also lacking, currently limiting the use of dapivirine as an alternative for women unable to take oral PrEP. At the current price, dapivirine is not cost-effective and unaffordable for inclusion in the South African Essential Medicines List.

Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension

HIV infections are ongoing globally despite efficacious biomedical prevention options. We sought to determine whether an HIV prevention package providing choice of daily pills or long-acting injectable cabotegravir and opportunities to change prevention options could increase biomedical prevention coverage and reduce new HIV infections. This study was an extension of three randomised trials that used SEARCH dynamic choice HIV prevention to recruit adults (aged ≥15 years) at risk for HIV from antenatal, outpatient, and community settings in rural Uganda and Kenya. In this 48-week open-label extension, participants maintained their original (1:1) randomisation group; the option to choose cabotegravir long-acting injectable was added for intervention participants. Inclusion criteria for the extension were previous enrolment in a SEARCH dynamic choice HIV prevention trial, negative HIV rapid test, and residence in study region. The intervention provided person-centred choice of oral pre-exposure prophylaxis (PrEP) or post-exposure HIV prophylaxis (PEP) or cabotegravir long-acting injectable, with the option to switch according to participant preference. The control provided standard-of-care access to oral PrEP and PEP, but not cabotegravir long-acting injectable. Biomedical prevention coverage (proportion of follow-up covered by oral PrEP, PEP, or cabotegravir long-acting injectable; primary outcome) and HIV incidence (secondary outcome) were compared between groups using targeted minimum loss-based estimation. The trial (NCT05549726) is closed to recruitment. Of 1534 participants initially randomly assigned (from April 15, 2021 to Sept 29, 2022), 984 (487 in the intervention group and 497 in the standard-of-care group) reconsented to the extension (from Jan 2 to March 3, 2023). The mean proportion of follow-up covered by biomedical HIV prevention was 69·7% (95% CI 64·9-74·5) in the intervention group versus 13·3% (10·2-16·3) in the standard-of-care group, corresponding to an absolute difference of 56·4 percentage points (95% CI 50·8-62·1; p<0·0001). The intervention significantly improved coverage across prespecified subgroups (sex and age groups). During the study, 274 (56%) of 485 intervention participants used cabotegravir long-acting injectable, 255 (53%) used oral PrEP, and ten (2%) used PEP. Among cabotegravir long-acting injectable initiators, 118 (43%) of 274 were not previously using oral PrEP or PEP. There were seven incident HIV infections in 390 person-years of follow-up in the standard-of-care group and no infections in 400 person-years of follow-up in the intervention group (incidence rate difference per 100 person-years 1·8, 95% CI 0·4-3·2; p=0·014). Offering people the choice of HIV biomedical prevention options including cabotegravir long-acting injectable in a flexible model can increase prevention coverage and reduce incident HIV infections. HIV programmes should support dynamic choice HIV prevention programmes that include effective oral and injectable long-acting products. National Institutes of Health.

A Mixed Methods Evaluation of Pharmacists' Readiness to Provide Long-Acting Injectable HIV Pre-exposure Prophylaxis in California.

Pre-exposure prophylaxis (PrEP) uptake remains low among people who could benefit, some of whom may prefer alternatives to oral PrEP, such as long-acting injectable pre-exposure prophylaxis (LAI-PrEP). We evaluated the potential for LAI-PrEP provision in pharmacies through a mixed methods study of pharmacists in California, where Senate Bill 159 enables pharmacists to independently provide oral PrEP. In 2022-2023, we conducted an online cross-sectional survey of California pharmacists and pharmacy students (n = 919) and in-depth interviews with pharmacists (n = 30), both of which included modules assessing attitudes about PrEP provision. Using log-binomial regression, we estimated prevalence ratios (PRs) comparing survey participants' willingness to provide LAI-PrEP by pharmacy- and individual-level characteristics. Qualitative interview data were analyzed using Rapid Qualitative Analysis to identify factors that may affect pharmacists' provision of LAI-PrEP. Half of the survey participants (53%) indicated that they would be willing to administer LAI-PrEP using gluteal injection in their pharmacy. Willingness was higher among participants who worked in pharmacies that provided vaccinations or other injections (56% vs. 46%; PR: 1.2; 95% confidence interval: 1.0-1.4) and/or oral PrEP under Senate Bill 159 (65% vs. 51%; PR: 1.3; 95% confidence interval: 1.1-1.5) than among participants whose pharmacies did not. Interviewed participants reported barriers to LAI-PrEP provision, including the need for increased training and staffing, a private room for gluteal injections, better medication access, and payment for services. Pharmacies offer a promising setting for increased LAI-PrEP access. However, pharmacists may require additional training, resources, and policy changes to make implementation feasible.

Preferences for pre-exposure prophylaxis delivery via online pharmacy among potential users in Kenya: a discrete choice experiment.

Oral pre-exposure prophylaxis (PrEP) is highly effective, but coverage remains low in high HIV prevalence settings. Initiating and continuing PrEP remotely via online pharmacies is a promising strategy to expand PrEP uptake, but little is known about potential users' preferences. We conducted a discrete choice experiment (DCE) to assess preferences for online pharmacy PrEP services. We partnered with MYDAWA, an online pharmacy in Nairobi, Kenya. Eligibility criteria were: ≥18 years, not known HIV positive, interested in PrEP. The DCE contained four attributes: PrEP eligibility assessment (online self-assessed, guided), HIV test type (provider administered, oral HIV self-test [HIVST], blood-based HIVST), clinical consultation (remote, in-person) and user support options (text messages, phone/video call, email). Additionally, participants indicated whether they were willing to uptake their selected service. The survey was advertised on MYDAWA's website; interested participants met staff in-person at a convenient location to complete the survey from 1 June to 20 November 2022. We used conditional logit modelling with an interaction by current PrEP use to estimate overall preferences and latent class analysis (LCA) to assess preference heterogeneity. Overall, 772 participants completed the DCE; the mean age was 25 years and 54% were female. Most participants indicated a willingness to acquire online PrEP services, with particularly high demand among PrEP-naive individuals. Overall, participants preferred remote clinical consultation, HIV self-testing, online self-assessment and phone call user support. The LCA identified three subgroups: the "prefer online PrEP with remote components" group (60.3% of the sample) whose preferences aligned with the main analysis, the "prefer online PrEP with in-person components" group (20.7%), who preferred in-person consultation, provider-administered HIV testing, and guided assessment, and the "prefer remote PrEP (18.9%)" group who preferred online PrEP services only if they were remote. Online pharmacy PrEP is highly acceptable and may expand PrEP coverage to those interested in PrEP but not accessing services. Most participants valued privacy and autonomy, preferring HIVST and remote provider interactions. However, when needing support for questions regarding PrEP, participants preferred phone/SMS contact with a provider. One-fifth of participants preferred online PrEP with in-person components, suggesting that providing multiple options can increase uptake.

Preferences for Delivery of HIV Prevention Services Among Healthcare Users in South Africa: A Discrete Choice Experiment.

Progress has been made to scale oral pre-exposure prophylaxis (PrEP) as part of combination HIV prevention, with the WHO recommending differentiated, simplified and demedicalized approaches. This study explored user preferences for components of a PrEP service delivery package, through a discrete choice experiment (DCE) among 307 people accessing primary healthcare services in South Africa between November 2022 and February 2023. Attributes included were: Source of information about HIV prevention and PrEP; Site for PrEP initiation and follow-up; Frequency of follow-up; PrEP pick-up point; HIV testing whilst using PrEP; Contact between appointments. A D-efficient DCE design was created with 16 choice sets in 2 blocks. DCE data were analysed using generalised multinomial logistic models. Compared to printed materials, participants preferred getting information about PrEP online (aOR = 7.73, 95% CI = 5.13-11.66) and through WhatsApp (aOR = 2.23, 95% CI = 0.98-5.55). PrEP initiation at a pharmacy or mobile clinic was valued equally to initiating PrEP at a clinic, but a community pop-up site was less preferred (aOR = 0.46, 95% CI = 0.33-0.64). There was a preference for 6-monthly over 3-monthly follow-up (aOR = 11.88, 95% CI = 5.44-25.94). Participants preferred collecting PrEP from a pharmacy (aOR = 5.02, 95% CI = 3.45-7.31), through home delivery (aOR = 2.18, 95% CI = 1.26-3.78) and from a vending machine (aOR = 1.43, 95% CI = 1.02-1.99) relative to where they initiated PrEP. Participants also preferred HIV self-testing over a healthcare provider test (aOR = 5.57, 95% CI = 3.72, 8.36). WhatsApp or Facebook groups (aOR = 4.12, 95% CI = 3.00-5.67), monthly phone calls (aOR = 2.84, 95% CI = 1.73-4.67) and weekly messages (aOR = 1.47, 95% CI = 1.10-1.97) were preferred contact between appointments, relative to no contact. To meet users' preferences, there is a need to expand decentralised and self-led HIV prevention services.

Peer-Delivered HIV Self-Testing, Sexually Transmitted Infection Self-Sampling, and Pre-exposure Prophylaxis for Transgender Women in Uganda: A Randomized Trial.

Peer-delivered HIV self-testing (HIVST) and sexually transmitted infection self-sampling (STISS) may promote adherence to oral pre-exposure prophylaxis (PrEP), but no studies have analyzed this approach among transgender women (TGW) in sub-Saharan Africa. The Peer study was a cluster randomized trial in Uganda (October 2020-July 2022; NCT04328025). Ten TGW peer groups, each with 1 TGW peer and 8 TGW, were randomized 1:1 to receive quarterly in-clinic HIV testing with PrEP refills as standard-of-care (SOC) or SOC plus monthly peer delivery of oral-fluid HIVST, STISS, and PrEP refills (intervention). Participants were followed for 12 months. The primary outcome was PrEP adherence. We screened 85 TGW and enrolled 82 (41 per arm). The median age was 22 years (interquartile range [IQR] 20-24). Twelve-month retention was 88% (72/82). At the 3, 6, 9, and 12-month clinic visits, 10%, 5%, 5%, and 0% of TGW in the intervention arm had TFV-DP levels ≥700 fmol/punch, versus 7%, 15%, 7%, and 2% in the SOC arm, respectively (P = 0.18). At all visits, any detectable TFV-DP levels were significantly higher in SOC than the peer delivery group (P < 0.04). PrEP adherence was associated with sex work (incidence rate ratio 6.93; 95% CI: 2.33 to 20.60) and >10 years of schooling (incidence rate ratio 2.35; 95% CI: 1.14 to 4.84). There was a strong correlation between tenofovir detection in dried blood spots and urine (P < 0.001). No HIV seroconversions occurred. Peer-delivered HIVST and STISS did not increase low levels of oral PrEP adherence among TGW in Uganda. Long-acting PrEP formulations should be considered for this population.

Engagement Along the PrEP Care Continuum Among Men Who Have Sex with Men in China: A Systematic Review and Meta-analysis.

Pre-exposure prophylaxis (PrEP), including daily oral, on-demand, and long-acting injectable (LAI), is a promising HIV prevention intervention for men who have sex with men (MSM). We conducted a systematic review on engagement with the PrEP continuum among MSM in China. A total of 756 studies were initially identified and 36 studies were included (N = 26,021). In the 20 studies (N = 13,886) examining PrEP awareness, 32.4% (95% CI: 25.1-40.7) of MSM were aware of PrEP. In the 25 studies (N = 18,587) examining willingness, 54.5% (95% CI: 41.9-66.5) MSM indicated they were willing to use PrEP. The pooled prevalence of PrEP uptake from 9 studies (N = 6,575) was 4.9% (95% CI: 1.4-15.8%), while pooled estimates of adequate adherence from five studies (N = 2,344) among MSM on PrEP was 40.7% (95% CI: 20.0-65.2%). Subgroup analyses suggested studies conducted after 2015 (versus before) tended to report higher awareness and uptake. Awareness was highest for daily oral PrEP, followed by on-demand, and LAI PrEP; willingness to use was highest for LAI PrEP. The operationalization of willingness and adherence constructs varied across studies and complicated the interpretation of pooled estimates. This review revealed gaps in the PrEP care continuum among MSM in China, with relatively low awareness and uptake (in contrast to willingness and adherence) as the major potential barriers to widespread implementation and the need for a unified approach to defining and measuring PrEP outcomes.

Adolescent Girls and Young Women Overcoming Adherence Challenges with Vaginal and Oral PrEP Use: A Longitudinal Qualitative Study from a Crossover Trial in South Africa, Uganda, and Zimbabwe.

Rates of HIV acquisition remain high among adolescent girls and young women (AGYW) in sub-Saharan Africa. We explored South African, Ugandan, and Zimbabwean AGYW's experiences in a crossover trial of two HIV prevention products: Daily oral pre-exposure prophylaxis pills and a monthly dapivirine vaginal ring. A subset of participants (n = 25) across all sites completed up to three serial in-depth interviews (SIDIs). The SIDIs explored barriers to product use, coping strategies, and the resulting outcomes. Coded textual data were analyzed using a product acceptability conceptual framework. Participants in the SIDIs described managing the array of challenges they encountered through formal adherence support, strategic product disclosure, and personally adapted strategies. For both products, perceived discreetness of the product and decision-making around disclosure was an important component of participants' narratives. Participants tailored their coping strategies based on available personal resources (e.g., cell phone alarms for PrEP reminders, social support through disclosure) or study provided resources (e.g., encouragement from staff, adherence groups). Notably, challenges participants encountered with each product during the crossover period helped inform product selection during the choice period. Our findings suggest that-even in a context where AGYW have access to several options for HIV prevention-challenges to consistent product use remain, but accessible support mechanisms and informed choice can help mitigate these challenges. Enacting that choice may also empower AGYW to reach their short and long-term life goals-including for HIV prevention. (NCT03593655, 20th July 2018).