The following brief was submitted at the conference:
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Safety and In Vitro Efficacy of a Topical Microbicide Gel for the Prevention of HIV-1 Transmission -
A. J. SONDERFAN^{1}, T. CHANCELLOR^{1}, R. W. BUCKHEIT, JR.^{2}, A. S. TYMS^{3}, J. C. JENSON^{1}, and A. T. PROFY^{1}.* ^{1}Procept, Inc., Cambridge, MA; ^{2}Southern Research Institute, Frederick Research Center, Frederick, MD; ^{3}MRC Collaborative Centre, London, UK. -
Heterosexual intercourse is the major route of HIV-1 transmission worldwide. In the absence of an effective vaccine or consistent male condom use, there is a clear need for female-controlled prevention technologies. We have identified an antiviral agent (PRO 2000) that is well suited for use as a vaginally applied microbicide to prevent HIV-1 transmission. The compound, a naphthalene sulfonate polymer of [approx]5000 MW, is simple to produce, stable for at least 12 months at 40øC, virtually colorless, and compatible with latex condoms. In vitro, PRO 2000 suppressed infection of both T cells and macrophages by a wide range of HIV-1 isolates, including primary clinical isolates and isolates of African origin. The compound also blocked infection by HSV-2, a cause of genital lesions that may potentiate HIV-1 infection. Topical gels containing 0.1%, 1.0% and 4.0% PRO 2000 were tested for tolerability in a rabbit vaginal irritation model. Female New Zealand White rabbits (5 per group) received daily 1-ml intravaginal doses of PRO 2000 gel, placebo gel, or an over-the-counter nonoxynol-9-containing spermicide for 14 days. None of the animals showed external signs of vaginal irritation or changes in body weight. Following necropsy, vaginal tissue sections (3 per animal) were evaluated for epithelial disruption, vascular congestion, edema, and leukocyte infiltration. Combined irritation scores were acceptable for all groups. However, the incidence of epithelial erosion was much lower in the three PRO 2000 groups (0/15, 1/15, and 1/15) than in the nonoxynol-9 group (7/15). PRO 2000 was not detectable in plasma following vaginal administration, indicating low systemic absorption. We conclude that PRO 2000 gel is well suited for evaluation as a topical microbicide to prevent HIV-1 transmission. Source: 4th Conference on Retroviruses and Opportunistic Infections - 1997 = |
