The Role of Rectal PrEP

Men who have sex with men (MSM) and transgender women (TGW) are disproportionately susceptible to HIV infection.

Patients who have anal sex are likely to have used OTC rectal preparations previously for anal fissures, anorectal ulcerations, hemorrhoids, and anorectal tears. Topical microbicides like tenofovir gel prevent disease transmission if applied to the rectum or vagina. The CAPRISA 004 trial suggested vaginal tenofovir 1% gel, when applied at the time of sexual contact, is effective, but 2 follow-up trials disagreed due to poor adherence.

Both tenofovir and cyanovirin (2 microbicides) have been shown to be effective rectally in nonhuman primate models, but in humans, certain factors influence adherence.

MSM have reported that up to 35 mL of gel comfortable and rectal preexposure prophylaxis (PrEP) are acceptable. The spermicide N-9 and hyperosmolar sexual lubricants increase the risk of HIV and other sexually transmitted diseases by inflaming the mucous membranes of the vagina and anorectum.

New study results published in PLOS One suggest tenofovir rectal gel is a safe method for preventing HIV transmission among young TGW and MSM.

The researchers enrolled HIV-negative individuals 18 to 30 years who were MSM or preoperative TGW at clinics in Pittsburgh, Boston, and San Juan into a cross-sectional assessment of sexual health and behavior. They also enrolled a 24-member subset of this cohort into a phase 1 clinical trial for tenofovir 1% gel.

The researchers employed high-resolution anoscopy to identify mucosal trauma and microscopic infections. Most participants were unaware of PrEP before enrollment and had expressed desire to initiate therapy.

The young MSM and TGW at high risk for HIV accepted rectal microbicide PrEP methods. Patient complaints included color, scent, ease of use, and unpleasant tactile feel after application.

Manufacturers may want to market rectal microbicides as pleasure enhancers, offer varying viscosities, and use a novel gel-specific applicator to increase uptake. High-risk patients, who are underrepresented in phase-1 clinical trials but have lower trial retention, are willing to use invasive PrEP methods. All 24 patients returned at follow-up (7 days later), but longer phase 2 and phase 3 trials (beyond 18 months) need to address participant ability to use the product consistently over time.

Ultimately, this phase 1 clinical trial showed tenofovir 1% rectal gel is safe and effective for preventing HIV infection in MSM and TGW. Phase 2 and phase 3 trials for tenofovir rectal gel will further explore this promising PrEP method.