AIDSWEEKLY Plus, Monday, 18 November 1996
Daniel J. DeNoon, Senior Editor

Several of the progesterone-treated animals also appeared to have accelerated progression of SIV disease compared to untreated controls.

"This study shows that SIV genital infection and disease course are enhanced by subcutaneous implants containing progesterone when compared to the rate of vaginal transmission in the follicular phase," wrote Preston A. Marx of the Aaron Diamond AIDS Research Center and his colleagues.

Marx et al. reported their findings in the journal Nature Medicine ("Progesterone Implants Enhance SIV Vaginal Transmission and Early Virus Load," Nature Medicine, 1996;2(10):1084-9). They noted that the intact vaginal mucosa present a barrier to SIV infection: a hundred to a thousand times more virus is required to infect a macaque monkey vaginally than by intravenous injection. Steroid hormones affect the vaginal mucosa, however.

"Progesterone thins the vaginal epithelium, increases the vaginal pH, reduces the amount of cervical mucus, and increases its viscosity, whereas estrogen produces the opposite effects," Marx et al. wrote.

To study the effects of progesterone in an experimental model, the researchers implanted subcutaneous pellets containing 200 mg of progesterone into 18 adult female rhesus macaques every 30 days for 90 days. A control group of 10 animals received placebo pellets. All of the monkeys were challenged with 1 milliliter of virus stock containing about 640 tissue culture infectious doses (TCIDs) of virus.

The authors pointed to several recent studies showing that this SIV dosage may be clinically relevant to doses to which women are exposed via the semen of an HIV infected sex partner.

Only one of the control animals became infected, and remained healthy, SIV seropositive, and SIV culture negative after 44 weeks.

In contrast, 14 of the progesterone-treated animals became infected, and three had rapidly fatal disease.

"In the rhesus macaque model we have shown that progesterone treatment of rhesus macaques results in atrophy of the vaginal epithelium and increased incidence of systemic SIV infection after intravaginal SIV exposure," Marx et al. concluded.

But there are a number of questions about the degree to which these findings are applicable to HIV exposed women using hormonal contraceptives.

"The results of these macaque studies point to a need for two types of studies in humans," Marx et al. cautioned. "The first is to test the effect of progestins on vaginal epithelium. The second is to conduct large prospective and case-control epidemiological studies to define whether or not synthetic progestins have any effect on HIV transmission in women."

The corresponding author for this study is Preston A. Marx, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, 7th Floor, New York, New York 10016.

This work was supported by the Contraceptive Research and Development (CONRAD) Program, Eastern Virginia Medical School, grant CSA-94-133 under a cooperative agreement (CCP-3044-A-002015-00) with the U.S. Agency for International Development (USAID); by a Mechanisms of AIDS Pathogenesis grant from the National Institutes of Health NIH AI 38573-02; by the National Cooperative Vaccine Development Group NIH AI 28147, and by Public Health Service grants RR 00168 and RR 07000.

961118
AW961106

Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsrx.net

Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.