The objective of this project is to better define the interaction between male genital tract inflammation (GTI) and HIV-l transmission. In previous studies we observed marked leukocytic infiltration of various urogenital organs in men with AIDS, a high prevalence of leukocytospermia [>10(6) white blood cells/ml semen, thought to be an indication of silent GTI] in HIV infected men, and a strong association between leukocytospermia and high titers of HIV-1 in semen. We hypothesize that GTI plays an important role in the sexual transmission of HIV-1 by recruiting infected cells to the urogenital tract, and/or by activating HIV-1 infected cells in urogenital tissues to produce virus. The proposed studies provide a combination of descriptive and hypothesis-driven research directed at better defining male genital tract inflammation and its sequelae in HIV-1 infected men, and the interaction between GTI, HIV-1 infection of male urogenital tract tissues, and the sexual transmission of HIV-1.
The specific aims of this project are: 1) to correlate titers of HIV-l DNA and RNA at various sites within the male genital tract or semen (measured by quanititative PCR) with qualitative and quantitative determinants of inflammation; 2) to quantify activated CD4+ T lymphocytes and macrophages in genital tract tissues and semen as a function of GTI, and to determine by FACS analysis whether these cells are principal cell types producing HIV-1 in semen; and 3) to better characterize GTI and its sequelae in HIV- 1 infected men. If asymptomatic GTI is a primary cofactor in HIV transmission, diagnosis and treatment of this condition could have a significant beneficial impact on the AIDS epidemic.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
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Brigham and Women's Hospital
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Politch, Joseph A; Xu, Chong; Tucker, Lynne et al. (2004) Separation of human immunodeficiency virus type 1 from motile sperm by the double tube gradient method versus other methods. Fertil Steril 81:440-7
Mayer, K H; Boswell, S; Goldstein, R et al. (1999) Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy. Clin Infect Dis 28:1252-9
Anderson, D J; Politch, J A; Tucker, L D et al. (1998) Quantitation of mediators of inflammation and immunity in genital tract secretions and their relevance to HIV type 1 transmission. AIDS Res Hum Retroviruses 14 Suppl 1:S43-9
Quayle, A J; Xu, C; Tucker, L et al. (1998) The case against an association between HIV-1 and sperm: molecular evidence. J Reprod Immunol 41:127-36
de los Santos, M J; Anderson, D J; Racowsky, C et al. (1998) Expression of interleukin-1 system genes in human gametes. Biol Reprod 59:1419-24
Quayle, A J; Xu, C; Mayer, K H et al. (1997) T lymphocytes and macrophages, but not motile spermatozoa, are a significant source of human immunodeficiency virus in semen. J Infect Dis 176:960-8