Background Tenofovir, a nucleoside reverse transcriptase inhibitor (NRTI), has been formulated as a vaginal film for topical microbicide development. To help inform studies to be conducted in a human population, we assessed safety factors in the pigtailed macaque model.

Methods The use of monkeys on this protocol was approved by the Institutional Animal Care and Use Committee at the University of Washington. Animals were handled humanely, and experiments were performed within the National Institutes of Health’s animal use guidelines, in compliance with the Guide for the Care and Use of Laboratory Animals and the Animal Welfare Act. Six pigtailed macaques underwent a three-arm cross-over design protocol comparing two doses of tenofovir films (40mg; 20mg) to a placebo film. Films used were 1/3 the size intended for human use. The drug content of macaque-sized test films was 11.2 ± 0.4 and 5.1 ± 0.3mg tenofovir/film. We administered the vaginal films to pigtailed macaques daily for five days one week, followed by four days the next week. Safety of repeated, daily exposures was measured by repeated colposcopic assessment, vaginal pH, vaginal smear and microbiology tracking.

Results Colposcopy revealed similar tissue appearance in all three study arms. There were no indications of product induced tissue disruption to vaginal or cervical mucosal surfaces. Vaginal microbiology assessments revealed similar shifts in flora prevalence across both the tenofovir formulations and the placebo study arm. Vaginal pH fluctuated similarly across all three study arms. Polymorphonuclear cell counts determined from Gram stained vaginal smears increased somewhat with exposure to the higher dose tenofovir formulation compared to the lower dose tenofovir and the placebo arms.

Conclusions Quick dissolving vaginal films, formulated to deliver tenofovir as a topical microbicide, are a promising alternative to gel formulations. Well designed clinical assessments of tenofovir film safety, pharmacokinetics, pharmacodynamics and product dispersal are warranted and ongoing.