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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Rankin, Tracy L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of North Carolina Chapel Hill
Internal Medicine/Medicine
Schools of Medicine
Chapel Hill
United States
Zip Code
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
Cottrell, Mackenzie L; Patterson, Kristine B; Prince, Heather M A et al. (2015) Effect of HIV infection and menopause status on raltegravir pharmacokinetics in the blood and genital tract. Antivir Ther 20:795-803
Dumond, Julie B; Yang, Kuo H; Kendrick, Racheal et al. (2015) Pharmacokinetic Modeling of Lamivudine and Zidovudine Triphosphates Predicts Differential Pharmacokinetics in Seminal Mononuclear Cells and Peripheral Blood Mononuclear Cells. Antimicrob Agents Chemother 59:6395-401
Sanders, Eduard J; Wahome, Elizabeth; Powers, Kimberly A et al. (2015) Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa. AIDS 29 Suppl 3:S221-30
Joseph, Sarah B; Swanstrom, Ronald; Kashuba, Angela D M et al. (2015) Bottlenecks in HIV-1 transmission: insights from the study of founder viruses. Nat Rev Microbiol 13:414-25
Rahangdale, Lisa; De Paris, Kristina; Kashuba, Angela D M et al. (2015) Immunologic, virologic, and pharmacologic characterization of the female upper genital tract in HIV-infected women. J Acquir Immune Defic Syndr 68:420-4
Bednar, Maria M; Hauser, Blake M; Ping, Li-Hua et al. (2015) R5 Macrophage-Tropic HIV-1 in the Male Genital Tract. J Virol 89:10688-92
Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J et al. (2014) Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis 14:281-90
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
Cohen, Myron S; Smith, M Kumi; Muessig, Kathryn E et al. (2013) Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here? Lancet 382:1515-24

Showing the most recent 10 out of 38 publications