Scholars@Duke publication: PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.

PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.

Publication , Journal Article

Keller, MJ; Zerhouni-Layachi, B; Cheshenko, N; John, M; Hogarty, K; Kasowitz, A; Goldberg, CL; Wallenstein, S; Profy, AT; Klotman, ME; Herold, BC

Published in: J Infect Dis

January 1, 2006

Published version (DOI) Link to item

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 (P < .001). 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.

Duke Scholars

Author Mary E Klotman Medicine, Infectious Diseases

Published In

J Infect Dis

DOI

10.1086/498533

ISSN

0022-1899

Publication Date

January 1, 2006

Volume

193

Issue

Start / End Page

27 / 35

Location

United States

Related Subject Headings

Vagina
Treatment Outcome
Therapeutic Irrigation
Polymers
Naphthalenesulfonates
Middle Aged
Microbiology
Macrophages
Humans
Herpesvirus 2, Human

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NLM

Keller, M. J., Zerhouni-Layachi, B., Cheshenko, N., John, M., Hogarty, K., Kasowitz, A., … Herold, B. C. (2006). PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial. J Infect Dis, 193(1), 27–35. https://doi.org/10.1086/498533

Keller, Marla J., Bouchra Zerhouni-Layachi, Natalia Cheshenko, Minnie John, Kathleen Hogarty, Andrea Kasowitz, Cindy L. Goldberg, et al. “PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.” J Infect Dis 193, no. 1 (January 1, 2006): 27–35. https://doi.org/10.1086/498533.

Keller MJ, Zerhouni-Layachi B, Cheshenko N, John M, Hogarty K, Kasowitz A, et al. PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial. J Infect Dis. 2006 Jan 1;193(1):27–35.

Keller, Marla J., et al. “PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.” J Infect Dis, vol. 193, no. 1, Jan. 2006, pp. 27–35. Pubmed, doi:10.1086/498533.

Keller MJ, Zerhouni-Layachi B, Cheshenko N, John M, Hogarty K, Kasowitz A, Goldberg CL, Wallenstein S, Profy AT, Klotman ME, Herold BC. PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial. J Infect Dis. 2006 Jan 1;193(1):27–35.