Determinants of HIV-1 Shedding in the Genital Tract of Women

There is evidence that HIV-1 transmission from mother to child and between sexual partners may be related to plasma viral load. Heterosexual transmission, and in many cases perinatal transmission, most probably occur through direct contact with virus present in the genital tract. Past studies of HIV-1 in the female genital tract have been in small cohorts or among women from Africa. Factors associated with genital tract shedding have included CD4 count, concentration of plasma HIV RNA, cervical mucus and ectopy, inflammation, use of hormonal contraceptives, pregnancy, vitamin A deficiency, and co-infection with other STDs. Other studies have shown that the genital tract has a distinct microenvironment that permits viral replication independent from the systemic circulation. The study of these potential sanctuaries of HIV-1 replication is of paramount importance.

This study involved a large cohort of HIV-1-infected women. It utilized women within the Women's Interagency HIV-1 Study (WIHS) in the Division of AIDS Treatment Research Initiative Study 009 (DATRI 009) -- a cross-sectional and multi-center, prospective study of the natural history of HIV-1 infection and associated diseases in women. WIHS women were eligible for this study if they were 18-45 years of age, were not pregnant, with an intact uterus and cervix, and were on stable antiretroviral therapy for 1 month. All women had a single assessment that included a history of antiretroviral therapy; HIV-1 related opportunistic and genital tract infections, STDs, physical examination, and blood collection. Between January 1997 and July 1998, 311 women were enrolled from five WIHS sites in the United States.

Findings from the study indicate that HIV-positive women may risk transmitting HIV to sexual partners and newborn infants through virus released in the genital tract, even when blood levels of HIV are low. Specific findings include data showing that 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. Of the women who had detectable viral RNA in their blood, 80 percent had HIV-1 shedding. Of those women who had positive virus cultures from their blood samples, 78 percent had HIV-1 shedding. About a third of the women who had low or undetectable RNA in their blood, as well as 39 percent of those whose blood cultures were negative for infectious virus had HIV-1 shed in the genital region.

In their conclusion, the authors said "concentration and presence of plasma HIV-1 RNA was the most significant factor in the predicting HIV-1 shedding. This information might be useful in the future for monitoring patients receiving antiretroviral therapy, and counseling patients about transmission risk to a sexual partner or to a newborn infant. However, a separate reservoir might exist for some women especially those receiving a protease inhibitor." The authors called for further controlled clinical research to assess the impact of antiretroviral and protease inhibitor on genital tract shedding and local resistance.

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