For the past 10 years we have focused on the biology of HIV in semen. Most recently we have used a novel HIV RNA detection strategy to identify people with acute HIV infection. We found that acute HIV infections are remarkably frequent in patients in our STD clinic in Malawi (>2% of all clients, AIDS, 2004). Such patients excrete so much HIV in semen that secondary sexual transmission becomes extremely likely. This renewal Application includes detailed studies of acute HIV infection in Malawi.
In Aim I we will recruit a longitudinal cohort of more than 200 men and women with acute HIV infection, and some of their sexual partners. We will evaluate the ability of simplified testing strategies to identify people with acute HIV infection.
In Aim II we will examine the dynamics of HIV replication in blood and semen to test the hypothesis that the concentration of HIV in semen decreases faster and to a lower level in semen than in blood. We will examine the degree of HIV viral diversity in seminal plasma at the time of transmission, and monitor viral change(s) over time. We will use the heteroduplex tracking assay (HTA) for this purpose. We will use fluorescence in-situ hybridization (FISH) to determine the number of seminal cells infected, and the number of HIV variants per cell. We will determine the infection status of sexual partners, and compare the HIV variants in concordant partners.
In Aim III we will examine the temporal CTL response in patients with acute infection. This response should predict the magnitude of viral burden over time, and the sight(s) of viral mutation. We will examine the CTL response in both HIV postive and negative sexual partners. We will use ELISPOT assays to examine the CTL response in seminal CDS cells. We will undertake prevention efforts directed at HIV negative partners, who are at considerable risk for HIV acquisition. We believe the studies proposed in this Application will provide unique insight into the biology of acute HIV infection and HIV transmission, and information critical for both biological and behavioral prevention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK049381-19
Application #
8668029
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Rankin, Tracy L
Project Start
1996-05-01
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
19
Fiscal Year
2014
Total Cost
$361,555
Indirect Cost
$109,235
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
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Thompson, Corbin G; Cohen, Myron S; Kashuba, Angela D M (2013) Antiretroviral pharmacology in mucosal tissues. J Acquir Immune Defic Syndr 63 Suppl 2:S240-7
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