2025/06/27 by José A. Bauermeister, Renata Arrington‐Sanders, J Coleman-Lewis +17 · 1 voice
Immunology and Microbiology · Medicine · #HIV Research and Treatment #HIV/AIDS Research and Interventions #HIV/AIDS drug development and treatment
paper · doi:10.1093/infdis/jiaf349
openalex publication_date 2025/06/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
BACKGROUND: Young men who have sex with men (YMSM) are disproportionately affected by human immunodeficiency virus (HIV); however, use of oral preexposure prophylaxis (PrEP) remains suboptimal. This study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and acceptability of a novel tenofovir (TFV) rectal microbicide douche for HIV prevention. METHODS: Eight HIV-negative YMSM (aged 18-24 years) participated in a single-dose, open-label trial. Each received 660 mg of TFV in a 125-mL rectal douche. Safety was assessed via clinical monitoring and adverse event (AE) reporting. PK analysis measured TFV and TFV-diphosphate (TFV-DP) concentrations in blood and rectal tissue. PD was evaluated using ex vivo HIV-1 challenge assays in rectal biopsies. RESULTS: No serious AEs occurred. Five mild to moderate AEs (eg, nausea, hyperglycemia) were reported, none related to the product. Median peak plasma TFV concentration (14.5 ng/mL) remained below levels seen with oral TDF. Median peak (24-hour) rectal tissue cell TFV-DP concentrations were 8319 fmol/106 cells with a corresponding 0.9 log10 HIV-1 p24 antigen reduction observed in ex vivo challenge assays. Rectal tissue TFV-DP concentrations exceeded those associated with on-demand oral 2-1-1 dosing from 1 to 72 hours and suppressed HIV-1 p24 antigen production in colonic explants. Acceptability was high: 87.5% reported satisfaction, and 75% would consider future use. CONCLUSIONS: The TFV rectal douche was safe, well tolerated, and acceptable to YMSM. Its favorable PK and PD profiles support further investigation as a behaviorally congruent, on-demand PrEP strategy. Additional studies are needed to assess long-term safety and efficacy in larger, more diverse populations. CLINICAL TRIALS REGISTRATION: NCT04686279.