These investigators have completed studies in Senegal that suggest that HIV-2 infection may be attenuated among untreated patients concurrently infected with HIV-2. They found that dually infected subjects had markedly lower mean plasma HIV-1 RNA levels, were 5.6 times more likely to have less than 400 HIV-1 RNA copies/mol, and had slower rates of CD4 count decline than were those with HIV-1 infection alone. In recent pilot studies, using and IFN-gamma ELISPOT assay to examine 18 HIV-1 and 9 dual HIV-1/2 injected subjects, lower plasma HIV-1 RNA levels were associated with the presence of Gag specific T cells with the ability to respond to HIV-2 Gag epitopes. Based on these findings, they hypothesize that these antigen-specific T cells provide a strong and stable immune defense against HIV-1 through MHC-restricted cytolytic T-cell activity, secretion of anti-viral cytokines and chemokines, and CD4+ T helper function. To test this hypothesis, they propose to: 1) confirm observations that the presence of HIV-2 Gag specific T cells enhances the host's ability to control HIV-2 infection and determine whether the ability to respond to other HIV-1 or HIV-2 epitopes (selected regions of nef, pol, env) provides additional control of HIV-1 infection. 2) Evaluate HIV-specific T-cell responses over time among those infected with HIV-1 alone and dually infected with both HIV-1 and HIV-2 in relationship to change in HIV-1 plasma viral load and CD4 count. 3) Determine the contribution of MHC-restricted class 1 CTL and release of anti-viral soluble mediators in observed control of HIV-1. 4) Delineate the contribution of HIV-2-specific CD4+ T helper cells in the control of HIV-1 infection. This study, which evaluates cellular immune responses in relation to viral load and CD4 count among untreated subjects who do and do not appear to be successfully controlling HIV-1 replication, offers the opportunity to define protective components of the host immune response to HIV. Identification of these responses may provide information relevant to future HIV vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048470-05
Application #
6748557
Study Section
Special Emphasis Panel (ZRG1-AARR-6 (02))
Program Officer
Dieffenbach, Carl M
Project Start
2000-09-29
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
5
Fiscal Year
2004
Total Cost
$571,118
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Hanisch, Rachel A; Cherne, Stephen L; Sow, Papa Salif et al. (2014) Human papillomavirus type 16 viral load in relation to HIV infection, cervical neoplasia and cancer in Senegal. Cancer Epidemiol 38:369-75
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