CROI 2025 Abstract eBook

Abstract eBook

Poster Abstracts

More than half of participants reported they would feel more protected from HIV with twice-yearly PrEP injections vs daily pills (baseline: 59%; W26: 58%; W52: 61%). Most participants reported they would feel more confident about not missing a PrEP dose with twice-yearly injections vs daily pills (baseline: 60%; W26: 59%; W52: 61%). Conclusions: Many participants reported a strong preference for twice-yearly injectable PrEP, whereas some indicated a preference for daily pills, highlighting the importance of choice. Importantly, many also felt that they were more likely to be protected from HIV, and remain adherent, on Q6M injections vs daily pills. Participant preference and clinical data strongly suggest twice-yearly LEN could increase the uptake of, adherence to, and persistence on PrEP among cisgender women.

serve to alert providers to re-engage with clients. Strategies to support long term engagement in PrEP care are needed, in particular for younger persons, those with high HIRI-MSM score, and known substance use.

1232 MK-8527 PK/PD Threshold and Phase II Dose Selection for Monthly Oral HIV-1 Preexposure Prophylaxis Yash Kapoor, Barbara Evans, Russ P. Carstens, Tracy Diamond, Anjana Grandhi, Gillian Gillespie, Peggy May Tan Hwang, Ryan Vargo, Randolph Matthews, Jesse C. Nussbaum, Rebeca M. Plank Merck & Co, Inc, Rahway, NJ, USA Background: MK-8527 is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) under clinical development as an oral monthly antiretroviral agent for prevention of HIV‑1 infection. MK‑8527 is phosphorylated intracellularly to the pharmacologically active triphosphate form, MK-8527-TP. Clinical and nonhuman primate data were incorporated into an assessment of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for MK-8527-TP to inform Phase 2 dose selection. Methods: A rhesus macaque preexposure prophylaxis (PrEP) model evaluating weekly oral doses of MK-8527 (ranging from 0.1 to 6.0 mg/kg) followed by weekly simian/human immunodeficiency virus (SHIV) intrarectal challenge was used to define a PK/PD threshold. In two Phase 1b studies, treatment naive participants with HIV-1 received a single oral dose of MK-8527 (0.25, 0.5, 1, 3, or 10 mg). Reduction in viral load (measured as log10 plasma HIV-1 RNA copies/ mL) and PK of MK-8527-TP in peripheral blood mononuclear cells (PBMCs) were used to establish an exposure-response relationship. A preliminary population PK model was used to simulate exposures across the Phase 1 studies to support dose selection in Phase 2. Results: Doses of MK-8527 ≥0.1 mg/kg provided protection against intrarectal acquisition of SHIV in rhesus macaques. In Phase 1b studies, the mean decrease in HIV-1 RNA at Day 7 post-dose was ≥1.0 log10 copies/mL following single doses of MK-8527 ≥0.5 mg. The totality of data from the rhesus macaque study and Phase 1b trials suggests that efficacy for HIV‑1 prevention is achieved with an approximate inhibitory quotient ranging from 1 to 3. A PrEP PK/PD threshold for MK-8527-TP was set at 0.03 pmol/million PBMCs for HIV-1 prevention which is ~3‑fold above the in vitro half-maximal inhibitory concentration (0.00972 pmol/million PBMCs) of MK-8527-TP against wild type HIV-1. Based on this PK/ PD threshold, and a preliminary population PK model, a ≥6-mg once-monthly oral dose of MK‑8527 would maintain MK-8527-TP levels above the PK/PD threshold in >90% of the population. Three oral dose levels of MK-8527 (3, 6, and 12 mg, administered monthly) were selected for the Phase 2 study. Conclusions: PK/PD results incorporating clinical and nonclinical data support efficacy and further development of MK-8527 doses up to 12 mg for monthly oral PrEP.

Poster Abstracts

1231 Characteristics of Persons Diagnosed With HIV in a Population-Based PrEP Program in British Columbia K. Junine Toy 1 , Raquel M. Espinoza 1 , Jason Trigg 1 , Wendy Zhang 1 , Erin Ready 2 , Paul Sereda 1 , David Moore 1 , Rolando Barrios 1 , Julio S. G. Montaner 1 1 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, 2 St Paul's Hospital, Vancouver, Canada Background: Publicly-funded oral HIV PrEP has been available to key populations in British Columbia (BC) through the BC Centre for Excellence in HIV/ AIDS since 2018. We examined differences in characteristics of PrEP enrollees with and without subsequent HIV diagnoses. Methods: We included clients with ≥1 PrEP prescription dispensed between 1-Jan-2018 and 31-Dec-2023 (follow-up to 30-Jun-2024). Baseline demographic, clinical, and PrEP prescription characteristics were reported (totals, and by HIV status at end of follow-up) using descriptive statistics. Wilcoxon rank sum and Fisher’s exact tests were used to compare variables between groups. Results: Overall, 12,389 clients were included, with median (Q1-Q3) age 32 (27-41) years, 95.8% were cis-men, 1.7% trans-women, 0.9% cis-women, 0.6% trans-men, and 0.5% non-binary. 12,152 (98.1%) identified as gay, bisexual or other men who have sex with men (MSM), and median HIV incidence risk index (HIRI-MSM) score was 18 (14-22). Clients had a median (Q1-Q3) of 6 (3-12) PrEP prescriptions over a median follow-up of 31 (15-58) months. Over the study period, 12,316 clients (99.4%) remained HIV negative and 73 (0.6%) were subsequently diagnosed with HIV at median (Q1-Q3) 32 (13-50) months after enrollment, median 10 (5-19) months after their previous negative HIV test, and median 13 (6-28) months after anticipated PrEP medication run out (based on dispensing records and once-daily dosing). Only 5 clients appeared to have PrEP medication supply at the time of diagnosis. Median (Q1-Q3) age was 31 (25-37) years; 71 were cis-men. Median (Q1-Q3) time to ART initiation after diagnosis was 7 (4-17) days. There were differences in age, proportion with HIRI-MSM score ≥25, known substance use and incident syphilis between clients with and without HIV diagnoses. Long terminal lapses in PrEP medication (max 67 months) and HIV testing (max 61 months) were also observed among seroconverters (Table). The new HIV diagnosis rate in the overall cohort was 0.19 per 100 PY (95% CI: 0.15-0.23) over 37,434 PY of follow-up. The rate was 0.12 per 100 PY (95% CI: 0.08-0.15) when follow-up was censored after 18 months. Conclusions: Few new HIV diagnoses occurred in enrollees engaged with PrEP medication. Incident syphilis, and lapses in HIV testing and PrEP dispensing may

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