Women With Low Levels Of HIV In Blood May Still Harbor Virus In Genital Tract

Heterosexual women with HIV-1—the type of HIV that accounts for most infections—apparently can expose others to the virus even when the women are thought to be on a successful regimen of antiretroviral drugs, the physicians report in the Nov. 10 issue of The Lancet.

Physicians know that measuring the concentration of HIV-1 RNA (the virus’s telltale genetic material) in the blood is the best predictor of a woman’s risk of transmitting HIV through heterosexual contact or during childbirth. However, direct contact with virus in the genital tract might be the necessary key to HIV transmission, according to Andrea Kovacs, M.D., associate professor of pediatrics and pathology at the Keck School.

Physicians at five centers across the nation enrolled 311 HIV-positive women for the study, analyzing samples of participants’ blood and taking swabs and a sterile saline wash of the genital tract. They measured the level of detectable viral RNA in blood and from genital tissues, and made cultures from both sources, as well. (Viral cultures serve as a measure of the virus’s infectious potential.)

Among the findings: - HIV-1 RNA was found in genital secretions of 57 percent of the women; cultured infectious virus from genital secretions was found in 6 percent of the women.

- Among women with detectable viral RNA in their blood, 80 percent had HIV-1 shedding in their genital tract; among those who had positive virus cultures from their blood samples, 78 percent had HIV-1 shedding in their genital tract.

- About a third of women (33 percent) with low or undetectable RNA in their blood—and 39 percent of those whose blood cultures were negative for infectious virus—did have HIV-1 shed in the genital region. Consistent with previous smaller studies, the team found that the greater the concentration of RNA in the blood, the greater the concentration of HIV-1 in the genital tract.

"Concentration and presence of plasma HIV-1 RNA was the most significant factor in predicting HIV-1 shedding," said Kovacs, director of the Comprehensive Maternal-Child and Adolescent HIV Management and Research Center at LAC+USC Medical Center. "This information might be useful in the future for monitoring patients receiving antiretroviral therapy, and counselling patients about transmission risk to a sexual partner or to a new-born infant."

But even women who had little virus evident in the blood still could release infectious HIV-1 from the cells of the uterus, cervix and surrounding tissues. "This suggests a separate reservoir of HIV-1 replication," Kovacs noted. The researchers propose that perhaps drugs’ effects or drug levels may vary across tissues, allowing for more replication of the virus in tissues of the reproductive tract than in blood, for example. Research already has indicated that the female genital tract is a distinct environment, where HIV-1 replicates differently than in the blood.

"More research in clinical trials is needed to assess the impact of antiretroviral therapy and protease inhibitors on genital tract shedding, and on the virus’s resistance to drugs in that region," Kovacs said.

Study participants were enrolled at sites in Los Angeles, San Francisco, Chicago, Washington, D.C. and Brooklyn, N.Y. The study was supported through the National Institute of Allergy and Infectious Diseases, the U.S. Department of Health and Human Services and the Women’s Interagency HIV Study.

Andrea Kovacs, Steven S. Wasserman, David Burns, David J. Wright, Jonathan Cohn, Alan Landay, Kathleen Weber, Mardge Cohen, Alexandra Levine, Howard Minkoff, Paolo Miotti, Joel Palefsky, Mary Young, Patricia Reichelderfer and the DATRI and WIHS Study Groups, "Determinants of HIV-1 shedding in the genital tract of women." The Lancet, Vol. 358, No. 9293, Nov. 10, 2001, pp. 1593-1601.