Abstract

HIV is primarily sexually transmitted, and men spread the disease more efficiently than women. HIV is transmitted in semen. In the absence of an effective vaccine and/or curative therapy, HIV control depends on understanding the factors which facilitate its transmission. Strong epidemiological evidence and perhaps the spread, of HIV. This phenomenon has been referred to as """"""""epidemiological synergy"""""""". However, the biological basis for epidemiological synergy has not been pursued. In particular, it could be postulated that the ejaculate from infected men contains a higher concentration of HIV. Whereas a variety of methods have been developed to quantitate HIV in blood and plasma, much less work has been done with semen. The proposal is designed i) towards the development and comparison of methods for quantification of HIV in semen; ii) to examine the prevalence of gonorrhea, chlamydia, and trichomonas, in asymptomatic HIV+ men; and iii) to determine whether men with asymptomatic urethral infection shed a greater concentration of HIV than an appropriate control group, and whether STD therapy reduces the shedding of HIV. In the first aim we will develop methods for quantification of HIV-1 in semen, including verification of assays to measure HIV-1 RNA in seminal plasma and correlation with HIV-1 in seminal cells.
In aim 2 we will study the dynamics of shedding of HIV in seminal plasma in a cohort of men at different stages of disease; correlate between the concentration of HIV in seminal and blood plasma; and examine the impact of potential cofactors affecting shedding of HIV in semen including mucosal inflammation caused by STDs.
In aim 3 we will determine whether treatment of urethritis reduces excretion of HIV-1 in semen. We believe that the goals of this application lend themselves to a better biological understanding of the transmission of HIV. We believe that this information will be important in further development of both behavioral and vaccine HIV prevention strategies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK049381-04
Application #
2905721
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Rankin, Tracy L
Project Start
1996-05-01
Project End
2000-06-30
Budget Start
1999-05-01
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Nicol, Melanie R; Emerson, Cindi W; Prince, Heather M A et al. (2015) Models for predicting effective HIV chemoprevention in women. J Acquir Immune Defic Syndr 68:369-76
Abrahams, Melissa-Rose; Treurnicht, Florette K; Ngandu, Nobubelo K et al. (2013) Rapid, complex adaptation of transmitted HIV-1 full-length genomes in subtype C-infected individuals with differing disease progression. AIDS 27:507-18
Miller, William C; Powers, Kimberly A; Smith, M Kumi et al. (2013) Community viral load as a measure for assessment of HIV treatment as prevention. Lancet Infect Dis 13:459-64
Gao, Feng; Scearce, Richard M; Alam, S Munir et al. (2009) Cross-reactive monoclonal antibodies to multiple HIV-1 subtype and SIVcpz envelope glycoproteins. Virology 394:91-8
Goonetilleke, Nilu; Liu, Michael K P; Salazar-Gonzalez, Jesus F et al. (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206:1253-72
Abrahams, M-R; Anderson, J A; Giorgi, E E et al. (2009) Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol 83:3556-67
Cohen, Myron S; Kashuba, Angela D M (2008) Antiretroviral therapy for prevention of HIV infection: new clues from an animal model. PLoS Med 5:e30
Price, Matthew A; Stewart, Scott R; Miller, William C et al. (2006) The cost-effectiveness of treating male trichomoniasis to avert HIV transmission in men seeking sexually transmitted disease care in Malawi. J Acquir Immune Defic Syndr 43:202-9
Pilcher, Christopher D; Eron Jr, Joseph J; Galvin, Shannon et al. (2004) Acute HIV revisited: new opportunities for treatment and prevention. J Clin Invest 113:937-45
Kaydos-Daniels, S Cornelia; Miller, William C; Hoffman, Irving et al. (2004) The use of specimens from various genitourinary sites in men, to detect Trichomonas vaginalis infection. J Infect Dis 189:1926-31

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