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PRO 2000 gel, a potential topical microbicide for HIV prevention, can block infection by other sexually transmitted disease pathogens.




 

Int Conf AIDS. 1998;12:620-1 (abstract no. 33146). Unique Identifier :

BACKGROUND: PRO 2000 is a 5-kD naphthalene sulfonate polymer that shows broad activity against HIV-1 in vitro. The compound is being developed as a topical microbicide to prevent transmission of HIV-1 and other sexually transmitted disease (STD) pathogens. Vaginal gels containing up to 4.0% PRO 2000 were well tolerated in human Phase I clinical trials. The goal of this study was to assess the activity of PRO 2000 against nonretroviral STD pathogens in vitro and in vivo. METHODS: PRO 2000 was tested for its ability to inhibit infection of human foreskin fibroblast cells by herpesviruses using a cytopathic effect or plaque reduction assay. It was also tested for its ability to inhibit intracellular infection of HeLa cells by Chlamydia trachomatis elementary bodies. In other studies, effects on Neisseria gonorrhoeae, Trichomonas vaginalis and vaginal lactobacilli were assessed following pretreatment with PRO 2000 (up to 1000 micrograms/ml). Finally, in a model for vaginal herpes simplex virus type 2 (HSV-2) infection, mice (15/group) were treated intravaginally with 15 microliters of 4.0% PRO 2000 Gel or placebo gel and then challenged with an HSV-2 stock. Survival was determined 21 days postinfection. RESULTS: PRO 2000 inhibited replication of HSV-1, HSV-2 and human cytomegalovirus with EC50 values of 0.45, < 0.03, and 10.1 micrograms/ml, respectively. The CC50 was > 100 micrograms/ml. Potent inhibition was achieved only when drug was added before viral inoculation. PRO 2000 also inhibited infection of HeLa cells by C. trachomatis elementary bodies = 0.6 microgram/ml), but was not cidal toward N. gonorrhoeae, T. vaginalis or vaginal lactobacilli at concentrations up to 1000 micrograms/ml. Vaginally applied PRO 2000 Gel protected 15/15 mice from genital HSV-2 disease, while only 2/15 animals treated with placebo gel survived viral challenge. CONCLUSIONS: PRO 2000 is active against herpesviruses and C. trachomatis at concentrations that are well tolerated in vivo. Infection by these pathogens is believed to potentiate HIV-1 transmission. PRO 2000 is not toxic to N. gonorrhoeae, T. vaginalis or healthy vaginal lactobacilli. Intravaginally applied 4.0% PRO 2000 Gel provided complete protection from genital HSV-2 disease in vivo, suggesting that the gel might also prevent HIV-1 transmission.

MEETING ABSTRACTS Administration, Intravaginal Animal Anti-Infective Agents, Local/*PHARMACOLOGY Clinical Trials, Phase I Disease Models, Animal Drug Screening Gels Human HIV Infections/*PREVENTION & CONTROL/VIROLOGY Mice Naphthalenes/*PHARMACOLOGY Sexually Transmitted Diseases/MICROBIOLOGY/*PREVENTION & CONTROL



 




Information in this article was accurate in December 30, 1998. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.