Contact with semen is the major mechanism for sexual transmission of HIV but there is little information on biological and cellular factors determining the rate, timing or levels of HIV in semen. The long-term goals of this research project are: to test the hypothesis that the HIV virus load in semen is highly variable over the course of infection and is influenced by both systemic and local urogenital factors; and develop strategies to reduce HIV transmission by lowering the virus load in semen. The three specific aims are to correlate shedding of HIV with host factors, cellular response in semen, and shedding of cytomegalovirus (CMV) in semen. The investigators will test the hypothesis that the male reproductive tract is distinct from the systemic compartment. The plan is to measure levels of HIV in semen and determine if shedding is more likely among men with advanced clinical stage of infection, genitourinary tract signs and symptoms, reduced cellular immune status in peripheral blood or those who are not on antiretroviral therapy. Regarding the cellular response in semen, the investigators plan to test the hypothesis that the local cellular response in semen limits shedding of HIV. Specifically, they will measure CD4, CD8 and polymorphonuclear cell counts and percentages in semen.Findings will be compared with titers of HIV viral forms and with isolation of virus in culture to determine if men with higher cell counts in their semen have lower titers of HIV. And finally, the investigators will test the hypothesis that shedding of CMV in semen enhances shedding of HIV. They will measure HIV and CMV titers in semen using polymerase chain reaction (PCR) and infectious virus using culture systems. The goal is to determine if shedding of CMV enhances the likelihood or titers of HIV in semen. The localization of HIV and CMV in semen fractions will also be compared.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK049477-04
Application #
2518468
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Badman, David G
Project Start
1994-09-30
Project End
1999-08-31
Budget Start
1997-09-15
Budget End
1999-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Urology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Stekler, Joanne; Sycks, Brian J; Holte, Sarah et al. (2008) HIV dynamics in seminal plasma during primary HIV infection. AIDS Res Hum Retroviruses 24:1269-74
Diem, Kurt; Nickle, David C; Motoshige, Alexis et al. (2008) Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV). AIDS Res Hum Retroviruses 24:561-71
Coombs, Robert W; Lockhart, David; Ross, Susan O et al. (2006) Lower genitourinary tract sources of seminal HIV. J Acquir Immune Defic Syndr 41:430-8
Lehrman, Ginger; Hogue, Ian B; Palmer, Sarah et al. (2005) Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 366:549-55
Zuckerman, Richard A; Whittington, William L H; Celum, Connie L et al. (2004) Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy. J Infect Dis 190:156-61
Speck, C E; Coombs, R W; Koutsky, L A et al. (1999) Risk factors for HIV-1 shedding in semen. Am J Epidemiol 150:622-31
Muller, C H; Coombs, R W; Krieger, J N (1998) Effects of clinical stage and immunological status on semen analysis results in human immunodeficiency virus type 1-seropositive men. Andrologia 30 Suppl 1:15-22
Krieger, J N; Nirapathpongporn, A; Chaiyaporn, M et al. (1998) Vasectomy and human immunodeficiency virus type 1 in semen. J Urol 159:820-5;discussion 825-6
Coombs, R W; Speck, C E; Hughes, J P et al. (1998) Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis 177:320-30
Krieger, J N (1995) New sexually transmitted diseases treatment guidelines. J Urol 154:209-13