Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Injectable antiretroviral therapy: best practice guide for nurses providing care to people living with HIV.

Oral antiretroviral therapy (ART) is extremely effective, allowing people living with HIV to have a normal life expectancy. Most treatments consist of oral tablets that must be taken at the same time every day for the rest of an individual's life. For a variety of reasons, some people cannot adhere to a daily regimen, resulting in a deterioration in their health. The introduction in 2021 of long-acting injectable ART has provided an alternative option for those who would prefer not to take oral therapy. This article provides an overview of the practicalities and challenges of setting up nurse clinics to administer these injections. It also highlights how this type of treatment has improved the quality of life for people receiving them. HIV nurse specialists are leading the way in delivering this innovative new treatment, and the article concludes by discussing which patients may benefit from injectables in the future. This guide is aimed at nurses who work within the HIV field or are supporting this treatment in other settings, for example in outpatient parenteral antimicrobial therapy (OPAT) services.

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

BACKGROUND: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy. METHODS: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use. MTN-044/IPM 053/CCN019 compared continuous or cyclic use of the DPV/LNG ring over 90 days of use. Safety was assessed by recording adverse events (AEs). DPV and LNG concentrations were quantified in plasma, cervicovaginal fluid, and cervical tissue. Vaginal bleeding was self-reported. RESULTS: There were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs with DPV/LNG ring vs. DPV ring use (p = .22), or with DPV/LNG ring continuous vs. cyclic use (p = .67). Higher plasma DPV concentrations were observed in users of DPV/LNG compared to DPV-only rings (Cmax p = 0.049; AUC p = 0.091). Plasma DPV and LNG concentrations were comparable with continuous and cyclic use (Cmax p = 0.74; AUC p = 0.25). With cyclic use, median nadir plasma DPV concentration was approximately 300 pg/mL two days after removal and median t1/2 for cervicovaginal fluid DPV concentration was 5.76 hours (n = 3). Overall bleeding experiences did not differ between continuous and cyclic users (p = 0.12). CONCLUSIONS: The extended duration DPV/ LNG rings were well tolerated and the observed DPV concentrations in plasma and cervicovaginal fluid when used continuously exceeded concentrations observed in previous DPV ring efficacy studies. LNG concentrations in plasma were comparable with other efficacious LNG-based contraceptives. Genital DPV concentrations had a short half-life and were thus not well sustained following ring removal.

Preference for novel biomedical HIV pre-exposure prophylaxis methods among adolescent girls and young women in Kampala, Uganda: a mixed methods study.

Background: Novel HIV pre-exposure prophylaxis (PrEP) methods including a potential future HIV vaccine, will increase prevention options for adolescent girls and young women (AGYW) at high risk of HIV infection in Eastern and Southern Africa, yet data on AGYW's preferences for various PrEP methods is limited. We investigated preferences for five biomedical PrEP methods (oral, injectable, vaginal ring, implant, HIV vaccine) among 14-24-years-old AGYW in Kampala, Uganda. Methods: From January to December 2019, we conducted a mixed methods study including 265 high-risk AGYW. After receiving two education sessions on the five PrEP methods, participants were asked about their "most preferred PrEP method." Multinomial logistic regression (oral PrEP as reference category) was used to determine participant characteristics associated with method preference. Results are presented as adjusted relative risk ratios (aRRR) with 95% confidence intervals (CI). In-depth interviews were conducted with 20 selected participants to examine reasons influencing PrEP preferences and suggestions for method improvements. Transcripts were analyzed thematically. Results: Participants preferred methods were: HIV vaccine (34.7%), oral PrEP (25.7%), injectable PrEP (24.9%), PrEP implant (13.6%), and vaginal ring (1.1%). Preference for injectable PrEP increased with every year of age (aRRR 1.22; 95% CI 1.04-1.44) and among participants with chlamydia or gonorrhoea (aRRR 2.53; 95% CI 1.08-5.90), while it was lower among participants having sexual partner(s) living with HIV or of unknown HIV status (aRRR 0.30; 95% CI 0.10-0.91). Preference for PrEP implants also increased with age (aRRR 1.42; 95% CI 1.14-1.77) and was strong among participants having ≥10 sexual partners in the past 3 months (aRRR 3.14; 95% CI 1.16-8.55), while it was lower among those with sexual partner(s) living with HIV or of unknown HIV status (aRRR 0.25; 95% CI 0.07-0.92). PrEP method preference was influenced by product attributes and prior experiences with similar product forms commonly used in health care. Conclusion: AGYW have varied preferences for biomedical PrEP method and those with higher sexual behavioral risk prefer long-acting methods. As we anticipate more available PrEP options, oral PrEP use should be supported among AGYW, especially for those with sexual partners living with HIV or of unknown HIV status.

Post-intervention perceptions on the antiretroviral therapy community group model in Trans Nzoia County, Kenya.

Introduction: the increasing number of people receiving antiretroviral therapy (ART) in sub-Saharan Africa has stressed already overburdened health systems. A care model utilizing community-based peer-groups (ART Co-ops) facilitated by community health workers (CHW) was implemented (2016-2018) to address these challenges. In 2018, a post-intervention study assessed perceptions of the intervention. Methods: forty participants were engaged in focus group discussions consisting of ART Co-op clients, study staff, and health care providers from Kitale HIV clinic. Data were analyzed thematically for content on the intervention, challenges, and recommendations for improvement. Results: all participants liked the intervention. However, some reported traveling long distances to attend ART Co-op meetings and experiencing stigma with ART Co-ops participation. The ART Co-op inclusion criteria were considered appropriate; however, additional outreach to deliberately include spouses living with HIV, the disabled, the poor, and HIV pregnant women was recommended. Participants liked CHW-directed quarterly group meetings which included ART distribution, adherence review, and illness identification. The inability of the CHW to provide full clinical care, inconvenient meeting venues, poor timekeeping, and non-attendance behaviors were noted as issues. Participants indicated that program continuation, regular CHW training, rotating meetings at group members´ homes, training ART Co-ops leaders to assume CHW tasks, use of pill diaries to check adherence, nutritional support, and economically empowering members through income generation projects would be beneficial. Conclusion: the intervention was viewed positively by both clinic staff and clients. They identified specific challenges and generated actionable key considerations to improve access and acceptability of the community-based model of care.

Preexposure prophylaxis for preventing HIV infection: Routine practice in primary care.

An estimated 1.2 million people in the United States have human immunodeficiency virus (HIV) infection per US Centers for Disease Control and Prevention 2021 data. The highest risk of HIV transmission occurs during injection drug use with needle sharing and during sexual activity, most significantly in condomless, receptive anal intercourse. Preexposure prophylaxis (PrEP) for the prevention of HIV infection is part of a larger biobehavioral strategy that uses antiretroviral medication, an oral formulation taken daily or during anticipated exposure events, or an injectable formulation administered every 8 weeks. PrEP consists of 3 possible regimens: emtricitabine/tenofovir disoproxil fumarate, emtricitabine/tenofovir alafenamide, or injectable cabotegravir. Primary care clinicians are strategically positioned to provide PrEP education and access.

Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

PrEP facilitators and barriers in substance use bridge clinics for women who engage in sex work and who use drugs.

BACKGROUND: Women who engage in sex work and use drugs (WSWUD) experience disproportionate HIV risks. Substance use treatment bridge clinics offer an opportunity to increase HIV pre-exposure prophylaxis (PrEP) delivery to WSWUD, but research on best practices is lacking. Therefore, we explored facilitators and barriers to PrEP across the PrEP care continuum in these settings. METHODS: Bridge clinic and affiliated harm reduction health service providers and WSWUD from Boston were recruited using passive and active outreach between December 2021 and August 2022. Participants were invited to take part in semi-structured phone or in-person interviews to explore HIV prevention and PrEP care experiences overall and within bridge clinic settings. Deductive codes were developed based on HIV risk environment frameworks and the Information-Motivation-Behavioral Skills model and inductive codes were added based on transcript review. Grounded content analysis was used to generate themes organized around the PrEP care continuum. RESULTS: The sample included 14 providers and 25 WSWUD. Most WSWUD were aware of PrEP and more than half had initiated PrEP at some point. However, most who initiated PrEP did not report success with daily oral adherence. Providers and WSWUD described facilitators and barriers to PrEP across the steps of the care continuum: Awareness, uptake, adherence, and retention. Facilitators for WSWUD included non-stigmatizing communication with providers, rapid wraparound substance use treatment and HIV services, having a PrEP routine, and service structures to support PrEP adherence. Barriers included low HIV risk perceptions and competing drug use and survival priorities. Provider facilitators included clinical note templates prompting HIV risk assessments and training. Barriers included discomfort discussing sex work risks, competing clinical priorities, and a lack of PrEP adherence infrastructure. CONCLUSION: WSWUD and bridge clinic providers favored integrated HIV prevention and substance use services in harm reduction and bridge clinic settings. Harm reduction and bridge clinic programs played a key role in HIV prevention and PrEP education for WSWUD. Effective behavioral and structural interventions are still needed to improve PrEP adherence for WSWUD.

Low clinical impact of HIV drug resistance mutations in oral pre-exposure prophylaxis: a systematic review and meta-analysis.

INTRODUCTION: Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM. METHODS: We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061. RESULTS: A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10). DISCUSSION: Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21). CONCLUSIONS: Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy: An executive summary.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed in the main document.

Consensus recommendations for the use of novel antiretrovirals in persons with HIV who are heavily treatment-experienced and/or have multidrug-resistant HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy.

Treatment options are currently limited for persons with HIV-1 (PWH) who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. Three agents have been approved by the U.S. Food and Drug Administration (FDA) since 2018, representing a significant advancement for this population: ibalizumab, fostemsavir, and lenacapavir. However, there is a paucity of recommendations endorsed by national and international guidelines describing the optimal use (e.g., selection and monitoring after initiation) of these novel antiretrovirals in this population. To address this gap, a modified Delphi technique was used to develop these consensus recommendations that establish a framework for initiating and managing ibalizumab, fostemsavir, or lenacapavir in PWH who are heavily treatment-experienced and/or have multidrug-resistant HIV-1. In addition, future areas of research are also identified and discussed.

Factors associated with ART interruption during the COVID-19 crisis in Burundi (the EPIC community-based research program).

With a national prevalence of 0.9%, Burundi is close to achieving UNAIDS' 2025 targets. Despite this, different types of crises periodically disrupt its HIV health services. The community-based program EPIC measured the impact of the COVID-19 health crisis on people living with HIV (PLHIV) in Burundi in 2021. Specifically, it assessed ART interruption and associated factors since the beginning of the pandemic. The study questionnaire was administered to PLHIV in three cities between October and November 2021. Participants were recruited using convenience sampling. Logistic regression models helped identify factors associated with ART interruption. Of the 317 respondents, 37 (11.7%) reported interruption. The majority (79.2%) self-identified as belonging to key populations. Interruption was significantly associated with: fewer HIV medical follow-up visits (adjusted Odds Ratio, aOR = 7.80, p = 0.001) and forced HIV status disclosure (aOR = 4.10, p = 0.004). It was inversely associated with multi-month ART dispensing (aOR = 0.36, p = 0.017) since the beginning of the pandemic and the perception of not having been sufficiently informed by the HIV medical team about the risk of COVID-19 infection (aOR = 0.11, p < 0.001). Our results highlight the importance of multi-month ART dispensing, enhanced communication, and voluntary disclosure of one's HIV status in preventing ART interruption in times of crises in Burundi.

Belgian 2024 guidance on the use of pre-exposure prophylaxis.

OBJECTIVES: We aimed to develop a guidance on the use of pre-exposure prophylaxis (PrEP) for HIV tailored to the Belgian context. METHODS: Different aspects of PrEP care were judged by an expert group of nine Belgian clinicians, seeking consensus for areas of controversies. RESULTS: PrEP should be considered in HIV negative patients at high risk of acquiring HIV. Currently, only oral tenofovir/emtricitabine is available in Belgium for PrEP, which can be used daily, or also event-driven in cisgender men and trans women who are not taking exogenous estradiol-based hormones. Personal counselling directed at medication adherence and sexual health should have a central role in PrEP care. At the initial assessment clinicians should give attention to symptoms of an acute HIV infection, the patients' immunization status and renal function. A regular follow-up must be set up to diagnose HIV seroconversion, treat sexually transmitted infections, and manage side effects of PrEP. CONCLUSION: The Belgian guidance on the use of PrEP provides a point of reference for standard PrEP care in Belgium and will be periodically updated.

Discontinuation of HIV oral pre-exposure prophylaxis: findings from programmatic surveillance within two general population HIV programs in Nigeria.

BACKGROUND: As oral PrEP scales up in Nigeria, information about uptake, use pattern and client preference in a real-world, implementation setting is invaluable to guide refining service provision and incorporation of oral PrEP and other prevention measures into routine health services. To add to this body of knowledge, our study examines factors associated with discontinuation of PrEP among HIV negative individuals across two large scale programs in Nigeria. METHODS: Using program implementation data from two large-scale HIV projects in Akwa Ibom and Cross River states in Nigeria between January 2020 and July 2021, we used logistic regression to explore factors associated with early discontinuation (i.e., stopping PrEP within one month of starting) among HIV-negative individuals who initiated PrEP in the programs. RESULTS: Of a total of 26,325 clients; 22,034 (84%) discontinued PrEP within the first month. The odds of PrEP discontinuation were higher among clients who enrolled in community-based distribution sites (aOR 2.72; 95% C.I: 2.50-2.96) compared to those who enrolled in program-supported facilities and never married (aOR 1.76; 95% C.I: 1.61-1.92) compared to married clients. Clients who initiated PrEP because of high-risk sexual behaviour (aOR 1.15, 95% C.I 1.03-1.30) or inconsistent use or non-use of condoms (aOR 1.96, 95% C.I 1.60-2.41) had greater odds of discontinuing PrEPthan those who initiated PrEP because they were in a serodifferent relationship. CONCLUSION: The behavioural and demographic factors associated with early discontinuation of PrEP suggest that risk stratification of pre-initiation and follow up counselling may be helpful in raising continuation rates. On the service delivery side, strategies to strengthen follow-up services provided by community-based distribution sites need to be introduced. Overall, the low continuation rate calls for a review of programmatic approaches in provision of PrEP services in Nigeria.

Virological non-suppression and associated factors among adult patients receiving antiretroviral therapy at selected health facilities in uMgungundlovu district of KwaZulu Natal, South Africa: a cross-sectional study.

Introduction: virological non-suppression is not only associated with increased risk of transmission of the Human Immunodeficiency virus (HIV) to others; perinatally and sexually, but it also decreases the life expectancy among the individuals who are on antiretroviral therapy (ART). This study sought to determine the level of virological non-suppression among ART patients from selected health facilities of a sub-district in uMgungundlovu district. This sub-district has high HIV transmission rates in KwaZulu Natal (KZN) and had one of the highest HIV prevalence in the district in 2018; population weighted HIV prevalence of 36.3% among men and women aged 15-49 years old, which was twice the average national prevalence of 18.8%. Methods: this descriptive, cross-sectional, and quantitative study was conducted among participants who were HIV-positive, 18 years old and above, and initiated on ART between January 2017 and January 2019 at selected PHC facilities of Vulindlela sub district. Health facility treatment registers, patient medical files and face-to-face interviews were used to collect the data and these were captured onto an Excel spreadsheet, cleaned, coded before importation into Epiinfo 17 for statistical analyses. Logistic regression analyses were conducted to investigate the factors associated with virological non-suppression. Results: the study found a majority of participants were females (240/401 (60%)). The mean age of the participants was 38.1 (SD=11.2), with most participants who were between the ages of 29 and 39 years old (167 (41.7%)). Virological non-suppression was observed among 10% (40/401) of participants. The odds of virological non-suppression were higher among participants who were married (aOR 4.76, 95% CI 1.49-15.19; p=0.008). Conclusion: a virological non-suppression of 10% translates to viral suppression of 90%, which is below the target of UNAIDS 95-95-95 strategy. Hiding and skipping medication indicate how non-disclosure continues to hinder HIV treatment adherence. High odds of virological non-suppression among married participants indicate non-disclosure of the positive HIV status, or lack in spousal support.

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study.

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective.

The future of PrEP: novel long-acting HIV prevention agents for adolescent women.

Adolescent girls and young women in Africa are at high risk of HIV and should be considered a key population for HIV prevention initiatives. Oral Tenofovir/Emtricitabine as pre-exposure prophylaxis (PrEP) has been shown to be effective on an individual and population level among key populations in Europe, Australia, and the US. However, studies in sub-Saharan Africa in a generalised epidemic have been less promising with adherence to daily tablets identified as a major problem. Long-acting PrEP drugs are being developed as a response to this problem. The first of these long-acting agents, injectable Cabotegravir given every two months has shown superiority to oral PreP and has been approved by the US Food and Drug Administration (FDA). Another long-acting PrEP drug in development is Lenacapavir which is an investigational, first-in-class long-acting HIV-1 capsid inhibitor that can be given as a six-monthly injection. These long-acting drugs could be a highly effective public health HIV prevention intervention. If made readily available to a vulnerable population of adolescent young women who are at high risk of HIV they could play an important role in protecting this key population against HIV and potentially reduce the population level risk of HIV.

Self-reported removal and expulsion of the dapivirine vaginal ring: qualitative reports from female ring users and their male partners in the Ring Study (IPM 027).

BACKGROUND/AIMS: The dapivirine vaginal ring is a self-administered, women-initiated, discreet, long-acting HIV-1 prevention option for women. It was found to be safe and effective in healthy HIV-negative women who adhered to product use instructions, and has been approved for use in women aged 18 and older in some African countries. A qualitative study was conducted to explore participants' and their male partners' discussions on accidental/purposeful vaginal ring removals during The Ring Study (IPM 027 clinical trial). METHODS: Data were collected via in-depth interviews and focus group discussions with female trial participants and their male partners, from seven research centres in South Africa and Uganda. Data were thematically analysed using NVivo. RESULTS: More participants reported purposeful ring removals than accidental expulsions. Various factors influenced purposeful ring removal - including individual (discomfort during use/sex and to clean it), partner (to show them, because of discomfort during sex, to test if partners could feel it, and concerns of harm), organisational (doctor's request), and socio-cultural (rumours about sickness and infertility). Some described their own ring use removal, others discussed why other participants removed their rings. CONCLUSIONS: Vaginal ring adherence is critical to improve and support product efficacy. Counselling on vaginal anatomy, vaginal ring insertion and importance of adherence is important to minimise vaginal ring removal. Couples counselling is also important to facilitate support and long-term vaginal ring adherence behaviour. Understanding factors influencing vaginal ring adherence is important for tailoring and targeting messages to support correct and consistent vaginal ring use as it is made available to the public.

The effect of care interruptions on mortality in adults resuming antiretroviral therapy.

OBJECTIVE: To estimate the relative rate of all-cause mortality amongst those on antiretroviral treatment (ART) with a history of interruptions compared with those with no previous interruptions in care. DESIGN: Retrospective cohort study. METHODS: We used data from four South African cohorts participating in the International epidemiology Databases to Evaluate AIDS Southern Africa collaboration. We included adults who started ART between 2004 and 2019. We defined a care interruption as a gap in contact longer than 180 days. Observation time prior to interruption was allocated to a 'no interruption' group. Observation time after interruption was allocated to one of two groups based on whether the first interruption started before 6 months of ART ('early interruption') or later ('late interruption'). We used Cox regression to estimate hazard ratios. RESULTS: Sixty-three thousand six hundred and ninety-two participants contributed 162 916 person-years of observation. There were 3469 deaths. Most participants were female individuals (67.4%) and the median age at ART initiation was 33.3 years (interquartile range: 27.5-40.7). Seventeen thousand and eleven (26.7%) participants experienced care interruptions. Those resuming ART experienced increased mortality compared with those with no interruptions: early interrupters had a hazard ratio of 4.37 (95% confidence interval (CI) 3.87-4.95) and late interrupters had a hazard ratio of 2.74 (95% CI 2.39-3.15). In sensitivity analyses, effect sizes were found to be proportional to the length of time used to define interruptions. CONCLUSION: Our findings highlight the need to improve retention in care, regardless of treatment duration. Programmes to encourage return to care also need to be strengthened.