Phase 1 study evaluates rectal tenofovir douche for PrEP

Rectal douches containing tenofovir might be a promising alternative to oral or injectable pre-exposure prophylaxis (PrEP), warranting their further development, according to results from a Phase 1 trial conducted in the U.S.

About This Study

“Tenofovir Douche as HIV Pre-Exposure Prophylaxis for Receptive Anal Intercourse: Safety, Acceptability, Pharmacokinetics, & Pharmacodynamics (DREAM 01)” was published online on Nov. 29, 2023, in The Journal of Infectious Diseases. The lead author is Ethel D. Weld, M.D., Ph.D., of the Department of Medicine (Clinical Pharmacology as well as Infectious Diseases) of Johns Hopkins University School of Medicine, in Baltimore, Maryland.

Key Research Findings

This phase 1, single study assessed the safety, acceptability, and pharmacological parameters of three tenofovir-based rectal douches to prevent HIV acquisition in 21 HIV-negative men who have sex with men. Most participants were white men, and the median age was 38 years old.

Participants used each of the three products once, with evaluation for one week thereafter, and a month-long washout period before trying the next douche. The douches were highly acceptable, with 94% of participants saying they would use them before receptive anal intercourse, if they were proven to prevent HIV acquisition.

Median peak tenofovir concentrations were significantly below trough concentrations of the oral formulation of tenofovir disoproxil fumarate used for PrEP. Colorectal drug concentrations were above those needed to prevent HIV acquisition for up to seven days after douche use. At that time, one of the three douches still exceeded drug concentrations reported from on-demand (rather than once daily) tenofovir disoproxil fumarate PrEP use.

After colorectal tissue was challenged with HIV in a petri dish, virus replication was significantly reduced compared to pre-dose baseline levels. While drug concentrations and preventive effects were similar to the oral drug, significantly less drug remained in the participant’s system beyond the site of potential virus transmission.

Discussion Highlights and Implications for Practice

While noting that further studies are required, the researchers believe that this preliminary study indicates that a single douche may provide a PrEP option that could be used on demand and aligns with the behaviors of many men who have receptive anal intercourse–douching prior to intercourse. Results show that it should be further developed as a potential alternative modality for PrEP, they concluded.

By Barbara Jungwirth