Associations Between Genital Tract Infections, Genital Tract Inflammation, and Cervical Cytobrush HIV-1 DNA in US Versus Kenyan Women
1Departments of Obstetrics & Gynecology, and 2Epidemiology 3University of Washington, Seattle Children's Research Institute 4Department of Medicine, Northwestern University 5Department of Medicine, University of Rochester 6Kenya Medical Research Institute 7Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 8Departments of Laboratory Medicine 9Pediatrics, University of Washington.JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2012; 62(2). DOI: 10.1097/QAI.0b013e318274577d
BACKGROUND:: Cervical HIV-1 DNA shedding is frequently detected among HIV-1-infected women (26-86% of specimens) despite potent suppressive antiretroviral therapy (ART) and may be a contributor to sexual HIV-1 transmission. The mechanisms responsible for HIV-1 DNA shedding are not well understood; elucidation of these mechanisms could be useful for prevention of sexual as well as perinatal HIV-1 transmission.We hypothesized that pro-inflammatory cytokines and co-infections in the female genital tract are associated with cervical HIV-1 DNA shedding. To test this hypothesis, we evaluated associations between vaginal pro-inflammatory cytokines, antiretroviral therapy, vaginal co-infections and HIV-1 DNA shedding in cervical cytobrush samples from HIV-1 infected women in the US and in Kenya. METHODS:: Specimens and clinical data were collected during prospective observational studies of HIV-1 infected women in Seattle, WA, Rochester, NY and Nairobi, Kenya between 2002-2009. Study participants were 18-50 years of age, non-pregnant and had no symptomatic genital infections at study entry. The University of Washington, University of Rochester and University of Nairobi Institutional Review Boards approved the studies, and all subjects provided written informed consent.
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ABSTRACT: A comparative analysis of cellular and soluble markers of immune activation in HIV-infected women on combination antiretroviral therapy (cART) showed that the upper (UGT) compared to the lower female genital (LGT) tract was characterized by higher frequencies of potential HIV target cells and increased inflammatory molecules. Despite the activated UGT milieu, HIV RNA could not be detected in paired samples of plasma, cervicovaginal (CVL) or endometrial lavage (EML). As ARV concentrations were ≥3 fold higher in the endometrium than the in the lower genital tract, high ARV penetration and/or metabolism may limit viral replication in the UGT.
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ABSTRACT: Human immunodeficiency virus (HIV)-infected leukocytes have been detected in genital secretions from HIV-infected men and women and may play an important role in the sexual transmission of HIV. However, they have been largely overlooked in studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candidates. This article describes the characteristics and quantities of leukocytes in male and female genital secretions under various conditions and also reviews evidence for the involvement of HIV-infected cells in both horizontal and vertical cell-associated HIV transmission. Additional research is needed in this area to better target HIV prevention strategies. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
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