The acquired immunodeficiency syndrome (AIDS) and related conditions result from infection with the human immunodeficiency virus (HIV). The mean interval between infection with HIV and the onset of AIDS is approximately 6-7 years. As of December 18, 1987, over 46,000 cases met the Centers for Disease Control definition of AIDS and the mortality was over 90 percent within 3 years of diagnosis. In limited studies HIV has been isolated from semen, supporting the epidemiologic observations that contact with semen is important for transmission of the virus. These findings are the basis for the recommendations for limiting transmission of HIV by """"""""safer sex"""""""" practices. However, very little information is available on the cells and organs of the male genitourinary tract where the virus resides and replicates, or on the consequences of infection for male reproductive function. The long-term goal of this proposal is to investigate the consequences of HIV infection for the male genitourinary tract at the organ and cellular levels to gain insight into the clinical consequences of this infection. There are three specific aims. First, we will examine the effects of HIV infection and stage of disease on the semen. Particular emphasis will be placed on determining the culture- and antigen-positivity of the semen, correlating these findings with the presence of culturable virus, T4/T8 lymphocyte subsets, and p24 antigen in the serum, the findings on semen analysts and the presence of pyosemia. Second, we will examine the localization of HIV infection within the genitourinary tract. We will concentrate on two aspects of this issue, the localization of infection within the male GU organs and the localization of infection within the semen. Localization of infection within the GU organs will be addressed at autopsy semen specimens, then determining HIV-culture and antigen-positivity of the seminal plasma and cellular fractions. In situ hybridization techniques will be used to complement other methods for detection of the virus. Third, we will examine the effects of vasectomy on HIV-culture and p24 antigen-positivity of the semen. Presence of culturable virus and antigen will be assayed in the semen before and after vasectomy in men who engage in heterosexual sexual activity. This pilot study may allow us to make additional recommendations for decreasing transmission of HIV in the semen of infected men. On the other hand, if vasectomy results in no change in the prevalence of HIV in the semen, then efforts to interrupt transmission of HIV should concentrate on organs distal to the vas deferens. Insights into the mehanisms of sexual transmission of HIV and the effects of HIV infection on male reproductive function may have major implications for decreasing transmission of this deadly infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040747-05
Application #
3241172
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Project Start
1988-09-15
Project End
1994-08-31
Budget Start
1992-09-01
Budget End
1994-08-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Krieger, J N; Coombs, R W; Collier, A C et al. (1991) Fertility parameters in men infected with human immunodeficiency virus. J Infect Dis 164:464-9
Krieger, J N; Coombs, R W; Collier, A C et al. (1991) Recovery of human immunodeficiency virus type 1 from semen: minimal impact of stage of infection and current antiviral chemotherapy. J Infect Dis 163:386-8