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.
