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

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.