Early events in HIV infection particularly the interplay between the virus and the initial host defense mechanisms, are likely to play major roles in determining the time frame or the subsequent progression to disease. understanding these components and how they dictate the outcome of this initial struggle between the virus and the host will provide important clues about the mechanism of HIV pathogenesis and correlates of protection against infection and disease progression. This program grant is dedicated to a comprehensive analysis of primary HIV infection ina unique study group from a highly endemic area of HIV transmission in Trinidad. The principal features of this cohort include large size, absence of bias for symptomatology, frequent sampling, long term follow-up for clinical endpoints and appropriately matched control subjects. The general aims of the study are to establish 1) relationships between early symptomatology and disease progression, 2) to provide a much finer resolution of the kinetic of HIV replication through frequent sampling and 3) to correlate a comprehensive range of host responses with viral replication. The ultimate goal of the program is to identify host responses that are most effective in suppressing HIV replication or in clearing the infection as well as those that are conducive to HIV dissemination and ultimately pathogenesis. Such information is likely to be important for design of preventive and therapeutic strategies that employ host defense mechanisms. The program is composed of four highly interactive projects led by experienced investigators that are tightly connected to a central Clinical Core. Overall management of the program will be effected by a Program Direction and Administration Core.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI040237-03
Application #
2672839
Study Section
Special Emphasis Panel (ZAI1-PRJ-A (80))
Project Start
1996-09-30
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Shen, Xiaoying; Parks, Robert J; Montefiori, David C et al. (2009) In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth. J Virol 83:3617-25
Tomaras, Georgia D; Yates, Nicole L; Liu, Pinghuang et al. (2008) Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J Virol 82:12449-63
Alam, S Munir; Scearce, Richard M; Parks, Robert J et al. (2008) Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. J Virol 82:115-25
Montefiori, David C; Altfeld, Marcus; Lee, Paul K et al. (2003) Viremia control despite escape from a rapid and potent autologous neutralizing antibody response after therapy cessation in an HIV-1-infected individual. J Immunol 170:3906-14
Montefiori, D C; Hill, T S; Vo, H T et al. (2001) Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection. J Virol 75:10200-7
Tokunaga, K; Greenberg, M L; Morse, M A et al. (2001) Molecular basis for cell tropism of CXCR4-dependent human immunodeficiency virus type 1 isolates. J Virol 75:6776-85
Ortiz, G M; Wellons, M; Brancato, J et al. (2001) Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects. Proc Natl Acad Sci U S A 98:13288-93
Tomaras, G D; Greenberg, M L (2001) CD8+ T cell mediated noncytolytic inhibition of human immunodeficiency virus type I. Front Biosci 6:D575-98
Demarest, J F; Jack, N; Cleghorn, F R et al. (2001) Immunologic and virologic analyses of an acutely HIV type 1-infected patient with extremely rapid disease progression. AIDS Res Hum Retroviruses 17:1333-44
Tomaras, G D; Lacey, S F; McDanal, C B et al. (2000) CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression. Proc Natl Acad Sci U S A 97:3503-8

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