Abstract

Most HIV infections are spread through sexual intercourse from men to their partners. We have studied the biology of HIV in semen to better understand the requirements of HIV transmission, and to develop clinical and public health interventions for prevention of HIV transmission. Our work suggests that high concentrations of HIV in semen can facilitate HIV transmission. We have demonstrated that gonococcal urethritis causes a tenfold increase in HIV excretion, which can be reversed with antibiotic treatment. Trichomonas vaginalis is a far more prevalent STD than Neisseria gonorrhoeae both in developed and developing countries. Our recent preliminary work suggests that symptomatic inflammatory trichomonas may cause the greatest increase in HIV excretion in semen.
In Aim 1 of this Application, we will study the effects of trichomonas on excretion of HIV RNA in seminal plasma. We will determine whether single dose metronidazole therapy (directed at T vaginalis) reduces excretion of HIV in semen. We will examine the relationship between the number of granulocytes in semen and the excretion of HIV. Conversely, we have shown that HIV excretion in semen can be reduced by antiretroviral drugs.
Aim 2 of this Application is designed to better understand the relationship between the concentration of selected antiretroviral drugs in semen (measured by Mass Spectroscopy), and their ability to reduce excretion of HIV in seminal plasma. We will examine the phosphorylation of nucleoside analogues in seminal cells. We will also examine the effects of antiretroviral therapy on replication of HIV in seminal cells. We will study the evolution of resistant HIV variants, and try to identify selective pressure(s) in the male genital tract which facilitate resistance. We will compare the """"""""fitness"""""""" of HIV variants in semen and blood. These studies will take advantage of a well-developed clinical infrastructure specifically designed to allow us to address complex biological issues. The results of these studies should provide further insight into the regulation of excretion of HIV in semen, transmission of HIV, and to inform public health HIV prevention policies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK049381-08
Application #
6635037
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (01))
Program Officer
Rankin, Tracy L
Project Start
1996-05-01
Project End
2005-04-30
Budget Start
2003-07-01
Budget End
2004-04-30
Support Year
8
Fiscal Year
2003
Total Cost
$448,531
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
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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