Cell-free and cell-associated HIV-1 has been detected in semen from HIV-infected subjects. Recent studies indicate HIV-1 variants present in semen could be different from those present in blood. This raises the possibility that viral dynamics in the male genital compartment is different than that in the blood and that blood is not the primary source of HIV-1 in semen, but a privileged site at the male genital organ, like prostate, may be the source of HIV-1 in semen. In this proposed study the investigators will 1) determine whether viral diversity in semen is related to shedding pattern of HIV-1 in semen, by comparing viral diversity in semen and blood from subjects with different patterns of HIV-1 shedding in semen, 2) determine the origin of HIV-1 in semen by analysis of HIV-1variants in parallel testis, prostate, blood and semen samples from seropositive subjects enrolled in the Pittsburgh portion of the Multicenter AIDS Cohort Studies (MACS), 3) determine the viral dynamics of HIV-1 in semen as compared to blood by the measurement of viral RNA levels in semen and blood collected from seropositive subjects at short intervals before and following potent antiretroviral therapy, 4) determine whether latent viral reservoirs in semen compartment is different than viral reservoir in blood in patients receiving potent antiretroviral therapy. Seminal mononuclear cells from patients receiving therapy for 2-3 years will be examined for proviral DNA by the highly sensitive PCR assay for viral RNA expression following in vitro cultivation using in situ PCR and nucleosin (a modified NASBA) assays. The investigators have assembled all of the resources and expertise to accomplish the stated specific aims in this proposal. The information from the proposed study will be extremely useful in the understanding of transmission and eradication of HIV following therapy.
|Craigo, Jodi K; Patterson, Bruce K; Paranjpe, Shirish et al. (2004) Persistent HIV type 1 infection in semen and blood compartments in patients after long-term potent antiretroviral therapy. AIDS Res Hum Retroviruses 20:1196-209|
|Paranjpe, Shirish; Craigo, Jodi; Patterson, Bruce et al. (2002) Subcompartmentalization of HIV-1 quasispecies between seminal cells and seminal plasma indicates their origin in distinct genital tissues. AIDS Res Hum Retroviruses 18:1271-80|