Oral Pre-exposure Prophylaxis Research Articles

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.

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 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.

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).

Oral Pre-Exposure Prophylaxis Innovative Interventions among Adolescent Girls and Young Women in South Africa: A Protocol Paper.

Although South Africa was the first country to register and roll out oral pre-exposure prophylaxis (PrEP) biomedical human immunodeficiency virus (HIV) prevention intervention in sub-Saharan Africa (SSA), its uptake remains low, particularly among adolescent girls and young women (AGYW). The uptake of PrEP may have worsened during the Coronavirus disease 2019 (COVID-19) pandemic. Some innovative interventions to improve PrEP uptake among AGYW have been implemented. This study aims to evaluate the effectiveness of PrEP innovative interventions implemented during COVID-19 towards reducing the risk of HIV infection among AGYW in South Africa. An exploratory, descriptive design will be conducted to carry out four study objectives. Firstly, to carry out a systematic review of innovative PrEP interventions implemented during COVID-19 in SSA countries. Secondly, to conduct a stakeholder analysis to identify PrEP stakeholders and interview them on their views on the implemented interventions. Thirdly, to assess the implementation outcomes of the innovative interventions using document reviews and Consolidated Framework for Implementation Research. Fourthly, to develop a framework for an improved PrEP service delivery among AGYW. Qualitative data will be captured in ATLAS.ti software (Technical University, Berlin, Germany) version 23 and analysed via thematic analysis. A statistical software package (STATA) version 18 (College Station, TX, USA) will be used to capture quantitative data and analyse them via descriptive analysis. The generated evidence will be used towards the development of framework, guidelines, and policies to strengthen the uptake of, scale-up, and adherence to PrEP among AGYW.

Interest in Oral Pre-exposure Prophylaxis Among Men Who Have Sex with Men and Transfeminine Persons in HPTN 075, a Multi-center HIV Prevention Study in Sub-Saharan Africa (2015-2017).

Use of oral pre-exposure prophylaxis (O-PrEP) for HIV prevention has not been fully utilized in sub-Saharan Africa, especially among key populations with high HIV incidence and prevalence, including men who have sex with men (MSM) and transgender women (TGW). We examined correlates of interest in O-PrEP among participants in the HIV Prevention Trials Network (HPTN) Study 075, a prospective cohort study, conducted between 2015 and 2017, across 4 sites in Kenya, Malawi, and South Africa. The study included persons assigned male sex at birth, between 18 and 44 years of age, who reported anal intercourse with a man in the past 3 months. Interest in O-PrEP and potential correlates were assessed among 297 participants who were HIV negative. 52% of the participants reported being aware of PrEP and 73% indicated interest in PrEP once informed about it. PrEP interest was not significantly associated with any of the surveyed demographic or psychosocial variables except study site. Our findings suggest a broad and general interest in O-PrEP among MSM and TGW in sub-Saharan Africa, despite relatively low awareness. While the situation around PrEP will have changed in the included countries, major questions about successful implementation still need to be addressed.

Evaluating the impact of HIV pre-exposure prophylaxis on pregnancy, infant, and maternal health outcomes in Malawi: PrIMO study protocol

BackgroundIncident HIV during the perinatal period significantly impedes elimination of Mother-to-Child HIV Transmission (eMTCT) efforts. Pre-Exposure Prophylaxis (PrEP) effectively reduces HIV acquisition, and new agents like injectable Cabotegravir (CAB-LA) offer potential advantages for pregnant and breastfeeding women. The Pregnancy, Infant, and Maternal health Outcomes (PrIMO) study will compare rates of composite adverse pregnancy outcomes, and infant adverse events, growth and neurodevelopment between mother-infant dyads receiving CAB-LA and those receiving oral PrEP in Malawi.MethodsPrIMO is an observational cohort study involving: (1) the development of a PrEP Pregnancy Registry for longitudinal surveillance of pregnant women on PrEP in Malawi; and (2) the enrolment of a prospective safety cohort of 621 pregnant women initiating oral PrEP or CAB-LA and their subsequent infants. The registry will include all women continuing or initiating PrEP during pregnancy across targeted sites in Lilongwe and Blantyre districts. The safety cohort will enrol a subset of those women and their infants from Bwaila District Hospital in Lilongwe, Malawi. We hypothesize that CAB-LA’s safety will be comparable to daily oral PrEP regarding adverse pregnancy outcomes, maternal/infant adverse events, and infant development. Participants in the cohort will choose either oral PrEP or CAB-LA and will be followed until 52 weeks post-delivery. Safety data will be collected from all mother-infant pairs and qualitative interviews will be conducted with a subset of purposively selected women (n = 50) to assess the acceptability of each PrEP modality.DiscussionThe PrIMO study will provide critical data on the safety of CAB-LA in pregnant and breastfeeding women and their infants. Results will guide clinical recommendations as the Malawi Ministry of Health prepares for the rollout of CAB-LA to this population. Evaluation of Registry implementation will inform its expansion to a nationwide safety monitoring system for PrEP use during pregnancy, with implications for similar systems in the region.Trial Registration numberNCT06158126. The study was prospectively registered (5 December 2023) in ClinicalTrials.gov.

Trajectories of Adherence to Oral Pre-exposure Prophylaxis and Risks of HIV and Sexually Transmitted Infections.

Pre-exposure prophylaxis (PrEP) effectiveness is highly dependent on medication adherence, which is associated with differential HIV risks and possibly sexually transmitted infection (STI). This retrospective cohort study of PrEP users (01/01/2012-12/31/2021) used the MarketScan database of commercially insured enrollees to examine PrEP adherence trajectory groups' associations with HIV and STI acquisition risks. Distinct PrEP adherence trajectories were identified by group-based trajectory modeling among individuals who used oral PrEP. The primary outcome was HIV acquisition incidence, and secondary was STI rate, compared among trajectory groups. Inverse probability treatment weighting time-varying Cox proportional hazards models assessed HIV acquisition, and Poisson regression models assessed STI. Among 23 258 oral PrEP users, 4 distinct PrEP adherence patterns were identified: minimal use (10.5% of the cohort), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%). Compared with the minimal use group, the gradually declining (adjusted hazard ratio [AHR], 0.53; 95% CI, 0.31-0.90) and consistently high (AHR, 0.50; 95% CI, 0.30-0.84) PrEP adherence groups showed decreased HIV incidence risks. Compared with the minimal use group, the rapidly declining (adjusted incidence rate ratio [AIRR], 1.35; 95% CI, 1.07-1.72), gradually declining (AIRR, 1.73; 95% CI, 1.38-2.18), and consistently high (AIRR, 2.06; 95% CI, 1.64-2.58) groups were associated with increased STI risk. These findings underscore the benefits of continuing and remaining adherent to PrEP and may also inform public health strategies, clinical guidelines, and interventions aimed at maximizing the effectiveness of PrEP in reducing new HIV infections while developing targeted strategies to prevent STIs with PrEP use.

HIV incidence in people receiving government-subsidised pre-exposure prophylaxis in Australia: a whole-of-population retrospective cohort study

HIV pre-exposure prophylaxis (PrEP) is highly effective and has been government subsidised in Australia since April, 2018. We examined HIV incidence over 5 years in a retrospective observational cohort of people who had received subsidised PrEP. Linked de-identified dispensing records for all government-subsidised oral PrEP, HIV antiretroviral therapy (ART), and hepatitis C treatment were used. We included all people dispensed subsidised PrEP from April 1, 2018, to March 31, 2023, and examined records up to Sept 30, 2023. Exposure was measured from date of first PrEP prescription and days covered by PrEP calculated for individuals based on quantity and date supplied. Assuming that HIV was diagnosed 30 days before ART initiation, we imputed the date of acquisition as the midpoint between the diagnosis and the later of the last PrEP prescription or 6 months before the diagnosis. We calculated HIV incidence and its predictors using Poisson regression. We included 66 206 people dispensed PrEP: 64 757 (97·8%) were men; median age was 33 years (IQR 27-43). 207 people acquired HIV, with an overall incidence of 1·07 per 1000 person-years (95% CI 0·93-1·23). Incidence was 2·61 per 1000 person-years among those dispensed PrEP once only. Using this group as a comparator, those with 60% or more days covered by PrEP had a 78·5% reduction in incidence (0·56 per 1000 person-years, p<0·0001) and those with less than 60% days covered had a 61·6% reduction (0·99 per 1000 person-years, p=0·0045). Independent predictors of HIV acquisition were a record of hepatitis C treatment (9·83 per 1000 person-years, adjusted incident rate ratio [aIRR] 8·70, 95% CI 4·86-15·56), only attending prescribers outside of areas with a high estimated prevalence of gay men (1·66 per 1000 person-years, aIRR 1·50, 1·08-2·09), age 18-29 years (1·33 per 1000 person-years, aIRR 1·56, 1·11-2·21), and earlier year of first PrEP. The low observed incidence of HIV among people receiving government-subsidised PrEP highlights the success of a national programme of oral PrEP scale-up in achieving sustained reduction in community HIV transmission. However, incidence varied greatly, indicating that more research is needed to understand why people were not taking PrEP at times of risk and emphasising the need for new interventions focused on this population to achieve elimination of HIV transmission. Individuals dispensed PrEP once only and less frequent users might benefit from more support. None.

Low knowledge levels and high willingness to use oral Pre-Exposure Prophylaxis (PrEP) among Key Populations in Kampala, Uganda: Implications for targeted educational interventions.

Preexposure prophylaxis (PrEP) reduces new human immunodeficiency virus(HIV) infections by up to 96% and is recommended for key populations by the World Health Organization. Understanding the knowledge and willingness to use PrEP is essential for effective implementation. This study assessed these factors and identifiedcharacteristics associated with differences in knowledge among key populations in Kampala, Uganda. We administered a cross-sectional survey to a systematic sample of 497 participants from fisherfolk (283, 56.9%), men who have sex with men (MSM) (93, 18.7%), and female sex worker (FSW) (121, 24.4%) communities in Kampala Central, where PrEP had not yet been rolled out. Data on sociodemographic characteristics, PrEP awareness, and HIV-related behavioralfactors were collected. Knowledge about PrEP was measured using an adopted questionnaire comprising five key questions about PrEP knowledge, graded as no knowledge, some knowledge and good knowledge. Ordered probit regression models were used to analyze the associations of independent factors with PrEP knowledge levels. Participants had a mean age of 29±7.6 years. Ofthese, 257 (51.7%) reported having sex with women, 157 (31.6%) with men and 83 (16.7%) with both men and women. Self-reported HIV-positive status was 6.4% in fisherfolk, 11.8% in MSM and 27.3% in FSW. PrEP awareness stood at 62.4% overall, with the highest awareness in FSW (73.6%) and the lowest in fisherfolk (54.1%). Willingness to use PrEP was high across all groups (77.7%), although it was lower among FSW (66.9%). Multivariate probit analysis highlighted key independent factors associated with PrEP knowledge among fisherfolks and HIV-related concerns (Adj. Coeff = 0.54, 95% CI: 0.11, 0.97) and lack of PrEP awareness (Adj. Coeff = -0.99, 95% CI:-1.28, -0.70); among MSM, lack of PrEP awareness (Adj. Coeff = -1.74, 95% CI:-2.38, -1.10); and in FSW, tertiary education (Adj. Coeff = 1.53, 95% CI: 0.07, 2.99) and marital status (Adj. Coeff = 0.57, 95% CI=0.09, 1.05). MEshighlighted the influence of these independent factors at each knowledge level. Despite the high willingness to use PrEP, significant knowledge gaps exist, particularly concerning dosage and use duration, which are influenced by factors such as HIV concern and educational attainment. Tailored educational initiatives may bridge these gaps and enhance willingness to use PrEP.

Applying CFIR to assess multi-level barriers to PrEP delivery in rural South Africa: Processes, gaps and opportunities for service delivery of current and future PrEP modalities

Despite established efficacy for oral pre-exposure prophylaxis (PrEP) in reducing HIV incidence, multi-level barriers within the health system, clinics, and the processes that shape practice have hindered service delivery and subsequent population-level effects. We applied the Consolidated Framework for Implementation Research (CFIR) to assess the context of PrEP delivery for adolescent girls and young women (AGYW) in rural South Africa and identify the factors supporting and impeding PrEP implementation to develop strategies to improve PrEP delivery. Between 2021 and 2022, we conducted in-depth interviews with five young women with PrEP use experience and 11 healthcare providers as well as four key informant stakeholder interviews. Tailored interviews organized around the CFIR domains provided multiple perspectives on the inter-connected processes, gaps, and opportunities between health systems, clinics, communities, and PrEP services. Shifts in PrEP policies, funding pressures, and inconsistent communications from the National Department of Health spurred fragmented planning, engagement, execution, and monitoring of PrEP delivery processes within clinics already struggling to address multiple population health needs. Resulting challenges included: conflicting priorities within clinics and across NGO partners, unclear goals and targets, staffing and space constraints, and insufficient community engagement. Individual clinics’ implementation climate and readiness to deliver PrEP varied in terms of operational plans and delivery models. Interviewees reported complexity of initiation procedures and support for PrEP maintenance, with opportunities to improve systems communications and processes to facilitate integrated services and more user-friendly experiences. Applying CFIR identified opportunities to strengthen PrEP delivery across levels within this complex service delivery setting.

Health impact, budget impact, and price threshold for cost-effectiveness of lenacapavir for HIV pre-exposure prophylaxis in eastern and southern Africa: a modelling analysis

Injectable lenacapavir administered every 6 months is a promising product for HIV pre-exposure prophylaxis (PrEP). We aimed to estimate the health and budget impacts and threshold price at which lenacapavir could be cost-effective in eastern and southern Africa. We adapted an agent-based network model, EMOD-HIV, to simulate lenacapavir scale-up in Zimbabwe, South Africa, and western Kenya from 2026 to 2035. Uptake assumptions were informed by a literature review of PrEP product preferences. In the main analysis, we varied lenacapavir coverage by subgroup: female sex workers (40% coverage); male clients of female sex workers (40%); adolescent girls and young women aged 15-24 years with more than one sexual partner (32%); women aged 25 years and older with more than one sexual partner (36%); and males with more than one sexual partner (32%). We also assessed a higher coverage scenario (64-76% across subgroups) and scenarios of expanding lenacapavir use, varying from concentrated among those at highest HIV risk to broader coverage including those at medium HIV risk. We estimated the maximum per-dose lenacapavir price that achieved cost-effectiveness (<US$500 per disability-adjusted life-year averted), infections averted, and 5-year budget impact, compared with daily oral PrEP only. In the main analysis, lenacapavir was projected to achieve from 1·6% (95% uncertainty interval [UI] 1·5-1·8) to 4·0% (3·4-5·1) population coverage across settings and to avert from 12·3% (5·4-19·5) to 18·0% (11·0-22·9) of infections over 10 years. The maximum price per dose was highest in South Africa ($106·28 [95% UI 95·72-115·87]), followed by Zimbabwe ($21·15 [17·70-24·89]), and lowest in western Kenya ($16·58 [15·44-17·70]). The 5-year budget impact was US$507·25 million (95% UI 436·14-585·42) in South Africa, $16·80 million (13·95-22·64) in Zimbabwe, and $4·09 million (3·86-4·30) in western Kenya. In the higher coverage scenario, lenacapavir distribution was projected to reach from 3·2% (95% UI 2·9-3·6) to 8·1% (6·8-10·5) population coverage and to avert from 21·2% (95% UI 14·7-18·5) to 33·3% (28·5-36·9) of HIV infections across settings over 10 years. Price thresholds were lower than in the main analysis: $88·34 (95% UI 83·02-94·19) in South Africa, $17·71 (15·61-20·05) in Zimbabwe, and $14·78 (14·33-15·30) in western Kenya. The 5-year budget impact was higher than the main analysis: $835·29 million (95% UI 736·98-962·98) in South Africa, $29·50 million (24·62-39·52) in Zimbabwe, and $7·45 million (7·11-7·85) in western Kenya. Expanding lenacapavir coverage resulted in higher HIV infections averted but lower price thresholds than scenarios of concentrated use among those with highest HIV risk. Our findings suggest that lenacapavir could avert substantial HIV incidence and that price thresholds and budget impacts vary by setting and coverage. These results could inform policy deliberations regarding lenacapavir pricing and resource planning. The Bill & Melinda Gates Foundation.

Oral HIV pre-exposure prophylaxis use and resistance-associated mutations among men who have sex with men and transgender persons newly diagnosed with HIV in the Netherlands: results from the ATHENA cohort, 2018 to 2022.

BackgroundIn the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known.AimWe assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands.MethodsData on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree.ResultsData on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs.ConclusionThe prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.

The pathway to delivering injectable CAB for HIV prevention: strategies from global PrEP leaders leveraging an adapted version of the Intervention Scalability Assessment Tool (ISAT)

BackgroundLonger-acting cabotegravir (CAB) is a novel, safe, and efficacious pre-exposure prophylaxis (PrEP) for HIV prevention. As we near a time for CAB scale-up, the experience of global leaders in PrEP research and implementation can be leveraged to identify optimal strategies for scaling and integrating CAB into existing PrEP infrastructure worldwide.MethodsWe recruited leaders of HIV prevention clinical trials and large PrEP programs through a combination of purposive and snowball sampling for participation in individual interviews. We conducted interviews using a semi-structured guide that compared CAB to oral PrEP and sought perspectives on barriers and strategies for CAB scale-up. Interviews were conducted virtually, audio recorded, and transcribed. We used thematic analysis, grounded in an adapted version of the Intervention Scalability Assessment Tool (ISAT), to identify critical elements for optimizing delivery of CAB.ResultsFrom October 2021 to April 2022, we interviewed 30 participants with extensive experience in PrEP research, care, and programming. Participants worked in all seven WHO regions and reported a median of 20 years working in HIV and 10 years in PrEP. Participants agreed that CAB was efficacious and discrete, therefore having the potential to address current concerns about oral PrEP adherence and stigma. Participants indicated direct and indirect costs for provider training, expansion of existing medical infrastructure, and the current medication cost of CAB as major concerns for roll out. The true cost to the end-user and health system were unknown. There were some conflicting strategies on how to best address product targeting, presentation of efficacy, and timing of product availability with scale-up. Some thought that targeting CAB for the general population could normalize PrEP and decrease stigma, while others thought that prioritizing key populations could optimize impact by targeting those with highest risk. Overall, participants emphasized that to ensure successful CAB scale-up, communities and stakeholders must be involved at every stage of planning and implementation.ConclusionsOur evaluation found that although there is a clear and urgent need for additional HIV PrEP options beyond daily oral PrEP, CAB scale-up must be thoughtful, flexible, and based in lessons learned from oral PrEP rollout.