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