Most HIV vaccine designs are currently based on studies of chronic HIV-1 subtype B infection. However, the prevailing dominance of HIV-1 subtype C (HIV-1 C) in the worldwide AIDS epidemic, and the efficient, albeit temporary, containment of the virus during acute HIV infection necessitates a comprehensive analysis of primary HIV-1 C infection with regard to vaccine design. Assuming that the level of viral set point is dictated by virus-host interactions, we postulated that (i) the kinetics of viral replication, viral diversity, and immune responses vary between primary HIV-1 infections; (ii) virological and immunological determinants in acute HIV-1 infection are related to viral set point, and (iii) virological and immunological parameters in acute HIV-1 infection associated with low viral set point could be identified and targeted for vaccine development. We hypothesize that a combination of functional Gag p24-specific T cell responses and low viral diversity within tat and nef in primary HIV-1 C infection is associated with low viral set point, while lack of functional p24-specific immune response coupled with high tat and nef diversity are markers of high viral set point. To test this hypothesis a prospective study on acute and early HIV-1 infection in Botswana has been designed. There are two Specific Aims in the study: 1. To characterize the magnitude, breadth and kinetics of virological and immunological determinants during primary HIV-1 C infection including transient changes in viral evolution and immune responses. Viral load (RNA and DNA), viral diversity (p24, tat, env, and nef), virus-specific CD4+ and CD8+ T cell immune responses, expression of CCR5 and CXCR4, and levels of beta-chemokine production (MIP-1a, MIP-1B and RANTES) will be analyzed. 2. To assess the association between virological and immunological markers in primary HIV-1 C infection with viral set point. To develop a multivariate model of the inter-relationship of these factors with viral set point.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI057027-03
Application #
7230930
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Young, Janet M
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$446,140
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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