Safety, Pharmacokinetics, and Acceptability of a Tenofovir Rectal Microbicide Douche Among Young Men Who Have Sex with Men: The DREAM ATN Study (ATN 163)

Abstract

Background: Young men who have sex with men (YMSM) are disproportionately affected by HIV, yet use of oral pre-exposure 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 (ages 18-24) 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 adverse events occurred. Five mild to moderate AEs (e.g., 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-hr) rectal tissue cell TFV-DP concentrations were 8,319 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.NCT: https://clinicaltrials.gov/study/NCT04686279.

Keywords: HIV prevention; PrEP; adolescents; douching; sexual minorities.