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

• Published in: The Lancet (British edition) Vol. 358; no. 9293; pp. 1593 - 1601
• Main Authors: Kovacs, Andrea, Wasserman, Steven S, Burns, David, Wright, David J, Cohn, Jonathan, Landay, Alan, Weber, Kathleen, Cohen, Mardge, Levine, Alexandra, Minkoff, Howard, Miotti, Paolo, Palefsky, Joel, Young, Mary, Reichelderfer, Patricia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 10.11.2001; Elsevier Limited
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Clinical trials; Cross-Sectional Studies; Female; Genital tract; Genitalia, Female - virology; HIV; HIV-1 - isolation & purification; Human immunodeficiency virus; Human papillomavirus; Humans; Laboratories; Leukocytes (mononuclear); Medical diagnosis; Middle Aged; Multicenter Studies as Topic; Peripheral blood mononuclear cells; Prospective Studies; Ribonucleic acid; Risk Factors; RNA; RNA viruses; RNA, Viral - blood; Secretions; Shedding; United States - epidemiology; Virus Diseases - diagnosis; Virus Diseases - epidemiology; Virus Shedding; Viruses; Women; United States; Los Angeles California; United States > US; Africa
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(01)06653-3

Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding. This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assesments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding. HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract 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 with negative PBMC cultures also had genital tract shedding. Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. However, HIV-1 shedding 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.