This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.In 2007, UNAIDS reported that women comprise 61% of adults in Sub-Saharan Africa living with HIV/AIDS. This highlights the critical need for an effective, female-controlled HIV prevention strategy such as a vaginally-applied microbicide gel, which can enable women to protect themselves from HIV infection. Unfortunately, recent trials using non-specific compounds (like cellulose sulfate) as gels have not been successful in blocking transmission. Combinations of potent antiretroviral agents with known success as therapy may be the most promising topical strategy for HIV prevention. Towards this goal, we have formulated a hydroxyethylcellulose-based gel containing two nucleoside/nucleotide reverse transcriptase inhibitors, emtricitabine (FTC) and tenofovir (TFV) in combination. In this study, we are testing the efficacy of the FTC/TFV gel as compared to placebo gel using a well-established repeated, low-dose exposure strategy in nonhuman primates. The study design mimics the conditions of high-risk sexual exposure to an HIV-like virus known as Simian/human Immunodeficiency virus (SHIV). Our results will provide much needed preclinical guidance for the potential use of FTC/TFV gel in preventing HIV infection in women. We have initiated an efficacy study using a repeat-exposure macaque model with low dose twice-weekly vaginal challenges with SHIV162P3, for a total of 14 challenges. Twelve female pigtail macaques have been assigned to a placebo gel arm (2% hydroxyethylcellulose) (n = 6) or 5% FTC/1% TFV (in 2% hydroxyethylcellulose) gel arm (n=6). FTC/TFV gel or placebo gel is applied vaginally to female pigtail macaques 30 minutes prior to challenge, and blood is collected immediately prior to challenge. Plasma viral load and plasma drug levels are determined after each blood collection.
Showing the most recent 10 out of 912 publications
