Leveraging A Digital Pill System to Understand Prevention-Effective Adherence to Oral Hiv Pre-Exposure Prophylaxis Among Men Who Have Sex with Men with Substance Use.

Daily oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, though efficacy depends on adherence. Digital pill systems (DPS) can enable direct, real-time adherence measurement. HIV-negative men who have sex with men (MSM) with substance use (excluding alcohol) utilized a DPS over 90 days and completed weekly surveys reporting sexual activity, condom use, and substance use. Responses indicating (1) any sexual activity and substance use or (2) condomless anal intercourse (CAI) in the prior week were categorized as high risk for HIV acquisition. PrEP adherence data for the 7-day period preceding each response was dichotomized as ≤ 3 and ≥ 4 doses/week, indicating prevention-effective adherence, and compared by HIV risk level. Thirteen MSM were analyzed (median age: 32). Of 113 surveys, 48.7% indicated high HIV risk, with 12.4% reporting CAI alone, 16.8% any sexual activity and substance use, and 19.5% both CAI and substance use. Weekly mean PrEP adherence was 90.3% (6.3 of 7 doses/week), with ≥ 4 doses/week recorded during 92.0% of weeks. The proportion of participants with ≥ 4 recorded doses/week was 88.9% during weeks with CAI alone, 89.5% during weeks with any sexual activity and substance use, 92.0% during weeks with both CAI and substance use, and 92.8% during lower risk weeks. Participants ingested ≥ 4 doses/week during 89.1% of all high-risk weeks and 94.8% of low-risk weeks. Overall, participants maintained high levels of PrEP adherence while engaging in HIV risk behaviors. DPS can be deployed concurrently with data collection tools to assess ingestion patterns during periods of elevated risk.

Qualitative accounts of PrEP discontinuation from the general population in Eswatini.

People in receipt of pre-exposure prophylaxis (PrEP) for the prevention of HIV in Sub-Saharan Africa often discontinue taking the medication. We conducted 27 semi-structured interviews with men and women who had started PrEP but did not return to the clinic for a refill after a 1, 2 or 3-month period. These 'discontinuation' clients were enrolled in a PrEP demonstration project for the general population in nurse-led, public-sector, primary-care clinics in Eswatini. Reasons for discontinuation included changes to self-perceived HIV risk such as the end of pregnancy and absent partners. Others described PrEP as inaccessible when working away from home and many described difficulties relating to a daily pill regimen and managing side effects. Female clients described being prohibited from using PrEP by their partners and co-wives. From these results, we recommend that client-centred counselling stresses the prevention-effective adherence paradigm, which promotes PrEP use in risk periods that are identifiable and PrEP discontinuation when the risk period has finished. A national scale up of PrEP may mitigate problems accessing PrEP. Extended counselling and support could assist with adherence and the management of side effects. Education and support for partners and families of PrEP clients may also contribute to better PrEP continuation.

PrEP initiation and discontinuation among transgender women in the United States: a longitudinal, mixed methods cohort study.

INTRODUCTION: Transgender women in the United States experience high HIV incidence and suboptimal Pre-exposure prophylaxis (PrEP) engagement. We sought to estimate PrEP initiation and discontinuation rates and characterize PrEP discontinuation experiences among a prospective cohort of transgender women. METHODS: Using a sequential, explanatory, mixed-methods design, 1312 transgender women at risk for HIV acquisition were enrolled from March 2018 to August 2020 and followed through July 2022 (median follow-up 24 months; interquartile range 15-36). Cox regression models assessed predictors of initiation and discontinuation. In-depth interviews were conducted among 18 participants, including life history calendars to explore key events and experiences surrounding discontinuations. Qualitative and quantitative data were integrated to generate typologies of discontinuation, inform meta-inferences and facilitate the interpretation of findings. RESULTS: 21.8% (n = 286) of participants reported taking PrEP at one or more study visits while under observation. We observed 139 PrEP initiations over 2127 person-years (6.5 initiations/100 person-years, 95% CI: 5.5-7.7). Predictors of initiation included identifying as Black and PrEP indication. The rate of initiation among those who were PrEP-indicated was 9.6 initiations/100 person-years (132/1372 person-years; 95% CI: 8.1-11.4). We observed 138 PrEP discontinuations over 368 person-years (37.5 discontinuations/100 person-years, 95% CI: 31.7-44.3). Predictors of discontinuation included high school education or less and initiating PrEP for the first time while under observation. Four discontinuation typologies emerged: (1) seroconversion following discontinuation; (2) ongoing HIV acquisition risk following discontinuation; (3) reassessment of HIV/STI prevention strategy following discontinuation; and (4) dynamic PrEP use coinciding with changes in HIV acquisition risk. CONCLUSIONS: PrEP initiation rates were low and discontinuation rates were high. Complex motivations to stop using PrEP did not consistently correspond with HIV acquisition risk reduction. Evidence-based interventions to increase PrEP persistence among transgender women with ongoing acquisition risk and provide HIV prevention support for those who discontinue PrEP are necessary to reduce HIV incidence in this population.

Alignment of adherence and risk for HIV acquisition in a demonstration project of pre-exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention-effective adherence.

INTRODUCTION: Adherence is essential for pre-exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life-long. PrEP is most efficient when its use is aligned with periods of risk - a concept termed prevention-effective adherence. The objective of this paper is to describe prevention-effective adherence and predictors of adherence within an open-label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project). METHODS: We offered PrEP to HIV-uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as "PrEP as a bridge to ART"). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with <100% condom use before six months of ART, low if they reported sex but had 100% condom use and/or six months of ART and very low if no sex was reported. We assessed prevention-effective adherence by cross-tabulating PrEP use with HIV risk and used multivariable regression models to assess predictors of ≥4 and ≥6 doses/week. Results A total of 985 HIV-uninfected participants initiated PrEP; 67% were male, median age was twenty-nine years, and 67% reported condomless sex in the month before enrolment. An average of ≥4 doses and ≥6 doses/week were taken in 81% and 67% of participant-visits, respectively. Adherence sufficient to protect against HIV acquisition was achieved in 75-88% of participant-visits with high HIV risk. The strongest predictor of achieving sufficient adherence was reporting sex with the study partner who was living with HIV; other statistically significant predictors included no concerns about daily PrEP, pregnancy or pregnancy intention, females aged >25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months  of follow-up, ART use >6 months  by the partner living with HIV and problem alcohol use. CONCLUSIONS: Over three-quarters of participant-visits by HIV-uninfected partners in serodiscordant couples achieved prevention-effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.