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.
|Osorio, Georgina; Hoenigl, Martin; Quartarolo, Jennifer et al. (2017) Evaluation of opt-out inpatient HIV screening at an urban teaching hospital. AIDS Care 29:1014-1018|
|Hoenigl, Martin; Braun, Dominique L; Kouyos, Roger et al. (2017) Evaluation of the Predictive Potential of the Short Acute Retroviral Syndrome Severity Score for HIV-1 Disease Progression in Individuals With Acute HIV Infection. J Acquir Immune Defic Syndr 74:e114-e117|
|Grebe, Eduard; Welte, Alex; Hall, Jake et al. (2017) Infection Staging and Incidence Surveillance Applications of High Dynamic Range Diagnostic Immuno-Assay Platforms. J Acquir Immune Defic Syndr 76:547-555|
|Chaillon, Antoine; Nakazawa, Masato; Wertheim, Joel O et al. (2017) No Substantial Evidence for Sexual Transmission of Minority HIV Drug Resistance Mutations in Men Who Have Sex with Men. J Virol 91:|
|Gianella, Sara; Taylor, Jeff; Brown, Timothy R et al. (2017) Can research at the end of life be a useful tool to advance HIV cure? AIDS 31:1-4|
|Green, Nella; Hoenigl, Martin; Chaillon, Antoine et al. (2017) Partner services in adults with acute and early HIV infection. AIDS 31:287-293|
|Gianella, Sara; Chaillon, Antoine; Mutlu, Ece A et al. (2017) Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals. AIDS 31:2059-2067|
|Vesa, Jouni; Chaillon, Antoine; Wagner, Gabriel A et al. (2017) Increased HIV-1 superinfection risk in carriers of specific human leukocyte antigen alleles. AIDS 31:1149-1158|
|Graves, Susannah K; Little, Susan J; Hoenigl, Martin (2017) Risk profile and HIV testing outcomes of women undergoing community-based testing in San Diego 2008-2014. Sci Rep 7:42183|
|Morris, Sheldon R; Zhao, Mitchell; Smith, Davey M et al. (2017) Longitudinal Viral Dynamics in Semen During Early HIV Infection. Clin Infect Dis 64:428-434|
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