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.
