P44.08
Background: Aminoglycosides, which restore the natural production of retrocyclins in the cervicovaginal mucosa, enhance innate antiviral immunity. Tobramycin, an aminoglycoside antibiotic, can be delivered by dissolvable vaginal films to heighten protection against sexually transmitted HIV-1 infection. This study assessed the safety of intravaginally delivered tobramycin in a macaque model for topical microbicide use.
Methods: In test product vs placebo studies of n=6 per group, we assessed the effects of a film formulation containing 5 mg tobramycin during two weeks of daily applications. We performed baseline colposcopy, vaginal microbiology, smear and pH measurements, followed by intravaginal film placement in each animal. Thirty minutes after film placement (test or placebo), repeat vaginal flora, smear and pH measurements were made. These procedures were repeated daily for five days in two successive weeks. On the following Monday (day 15), a follow-up exam was conducted to document recovery.
Results: Colposcopic observations demonstrated that repeated exposures to the 5mg tobramycin film did not lead to serious adverse findings, i.e. cervicovaginal tissue abrasion and/or friability, in any of the 6 animals. Microbiologic assessment revealed populations of H2O2 producing lactobacilli and viridans streptococci fluctuated over the course of the experiment, but no clear trend of growth or suppression was noted for either organism. The incidence of enteroccocus and E. coli remained low, yet each was more prevalent at the end of the study than at baseline. In both study arms, vaginal pH measures fluctuated modestly throughout the study, and on average decreased from neutral pH at baseline to pH 5.5-6.0 at the final visit. No product related induction of neutrophil infiltration was noted by Gram stain.
Conclusions: Repeated vaginal exposures to the aminoglycoside film were well tolerated in the macaque model. Studies assessing systemic absorption and distribution of tobramycin in this experiment are underway.
