Determinants of HIV-1 shedding in the genital tract of women

Background Plasma HIV-1 RNA concentration has been the best predictor for r isk of heterosexual and perinatal transmission. However, direct contact wit h HIV-1 present locally in the genital tract might be necessary for transmi ssion. We aimed to assess the relation between HIV-1 shedding (RNA or cultu rable virus) in female genital secretions and other factors that might affe ct HIV-1 shedding. Methods This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-Infected wome n. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assessments, cultured HIV-1, and measured RNA in peripheral b lood mononuclear cells (PBMC) and genital secretions. We compared the resul ts with univariate and multivariate analyses. Presence of HIV-1 RNA or cult urable virus in genital secretions was defined as HIV-1 shedding. Findings HIV-1 RNA was present in genital secretions of 57% (152/268) of wo men whereas infectious virus was detected only in 6% (17/271). Genital trac t HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those wit h negative PBMC cultures also had genital tract shedding. Interpretation Plasma RNA concentration, both qualitatively and quantitativ ely, was the most important factor in predicting genital HIV-1 shedding, ev en among women receiving potent antiretroviral therapy. However, HIV-1 shed ding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some women.