Project 2 (Transmission Correlates) will characterize the biological, viral, and host correlates of HIV sexual transmission. The Clinical and Specimen Core will identify study subjects and provide the blood and genital secretion specimens for the research projects. Project 1 (Transmission Probability) will ascertain rates of transmission and generate epidemiological and behavioral data. The Administrative Core will coordinate these activities together with data management, and provide the statistical and analytical resources to permit robust and valid conclusions regarding the data.
Aim 1 of Project 2 will measure the biologic correlates of sexual transmission of HIV. These include viral loads in blood and the genital tract, lymphocyte numbers in genital secretions, and the presence of viral and bacterial sexually transmitted infections.
This aim will also address whether sexually transmitted HIV infection is mediated by cell-free virus or by virus-infected lymphocytes.
Aim 2 will assess the viral correlates of sexual transmission of HIV. Extensive nucleotide sequencing will extend our published observations characterizing virus in the genital compartment. The objective will be to characterize the genotypic and phenotypic characteristics of transmitted HIV-1 variants.
Aim 3 will investigate host determinants of sexual transmission of HIV. We will extend our studies of the neutralizing antibody response to HIV infection by determining the role of neutralizing antibody in blood and the genital tract in selecting for transmitted viral variants. The other two components of the aim will leverage our well characterized study subjects and their clinical specimens with two internationally recognized laboratories with longstanding collaborations with our group. Dr. Sunil Ahuja from the University of Texas Health Sciences Center will characterize the host genetics of both index subjects and their transmitting partners. Drs. Walker, Allen, and Altfeld from Harvard Medical School will provide full length HIV genome sequencing, viral phenotype, and CTL analyses that will characterize the role of cell mediated immunity, escape, and fitness. Each of these Aims is designed to address specific hypotheses. The data collected in Project 2, together with the epidemiologic and behavioral data from Project 1, will permit comprehensive analyses to determine which parameters are confounding, dependent, or independent determinants of HIV sexual transmission. These insights should provide important leads into the design of better vaccine candidates and other preventive strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI074621-05
Application #
8375407
Study Section
Special Emphasis Panel (ZAI1-MH-A)
Project Start
2008-03-15
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2012
Total Cost
$1,073,612
Indirect Cost
$331,389
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Hoenigl, Martin; Green, Nella; Camacho, Martha et al. (2016) Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening. Emerg Infect Dis 22:532-4
Gianella, Sara; Letendre, Scott (2016) Cytomegalovirus and HIV: A Dangerous Pas de Deux. J Infect Dis 214 Suppl 2:S67-74
Hoenigl, Martin; Little, Susan J (2016) How can we detect HIV during the acute or primary stage of infection? Expert Rev Mol Diagn 16:1049-1051
Hoenigl, Martin; Graff-Zivin, Joshua; Little, Susan J (2016) Costs per Diagnosis of Acute HIV Infection in Community-based Screening Strategies: A Comparative Analysis of Four Screening Algorithms. Clin Infect Dis 62:501-11
Chaillon, Antoine; Hoenigl, Martin; Mehta, Sanjay R et al. (2016) A practical online tool to estimate antiretroviral coverage for HIV infected and susceptible populations needed to reduce local HIV epidemics. Sci Rep 6:28707
Hoenigl, Martin; Chaillon, Antoine; Moore, David J et al. (2016) Clear Links Between Starting Methamphetamine and Increasing Sexual Risk Behavior: A Cohort Study Among Men Who Have Sex With Men. J Acquir Immune Defic Syndr 71:551-7
Hoenigl, Martin; Chaillon, Antoine; Kessler, Harald H et al. (2016) Characterization of HIV Transmission in South-East Austria. PLoS One 11:e0151478
Dan, Jennifer M; Massanella, Marta; Smith, Davey M et al. (2016) Brief Report: Effect of CMV and HIV Transcription on CD57 and PD-1 T-Cell Expression During Suppressive ART. J Acquir Immune Defic Syndr 72:133-7
Kassanjee, Reshma; Pilcher, Christopher D; Busch, Michael P et al. (2016) Viral load criteria and threshold optimization to improve HIV incidence assay characteristics. AIDS 30:2361-71
Yang, S; Lok, J J (2016) A goodness-of-fit test for structural nested mean models. Biometrika 103:734-741

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