PRO 2000 Gel Inhibits HIV and Herpes Simplex Virus Infection Following Vaginal Application: A Double-Blind Placebo-Controlled Trial
Departments of 1Medicine, 2Pediatrics, and 3Community Medicine, Mount Sinai School of Medicine, New York, New York; 4Indevus Pharmaceuticals, Lexington, Massachusetts
Background. Microbicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing to clinical trials on the basis of activity observed in vitro and in animal models. However, no data demonstrate activity of microbicides after application in humans. This study was designed to determine the antiviral activity in cervicovaginal lavage (CVL) samples collected after intravaginal application of 0.5% PRO 2000 gel (Indevus).
Methods. A randomized, double-blind study was conducted to assess the anti-HIV and anti–herpes simplex virus (HSV) activity of PRO 2000 in CVL samples obtained at screening (48 hours before) and 1 hour after application of study or placebo gel. HeLa cells or human macrophages were inoculated with CVL samples spiked with replication-defective HIV containing a luciferase indicator gene and pseudotyped with an R5 envelope. Human cervical epithelial cells were inoculated with CVL samples and challenged with HSV-2(G), and the virus titer was then determined.
Results. CVL samples obtained after application of PRO 2000 gel significantly inhibited HIV and HSV infection by at least 1000-fold, compared with CVL samples obtained at screening (
). There were no differences in cytokine levels between the drug and placebo groups.
Conclusions. PRO 2000 gel (0.5%) is sufficiently bioavailable and retains substantial antiviral activity after intravaginal application. This strategy provides a mechanism for testing the efficacy of a microbicide before embarking on large-scale clinical trials.
Received 17 May 2005; accepted 21 July 2005; electronically published 17 November 2005.
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Presented in part: Microbicides 2004, London, 30 March 2004 (oral presentation 02603); 12th Conference on Retroviruses and Opportunistic Infections, Boston, 24 February 2005 (abstract 535).
Financial support: National Institutes of Health (grants HD-43733 and RR-00071 and training grant AI-07623 to M.J.).
Potential conflicts of interest: A.T.P. is a full-time employee of Indevus Pharmaceuticals, the developers of PRO 2000 gel, and holds equity interest in the company. All other authors: none reported.
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(See the article by Dhawan and Mayer, on pages 36–44.)







