This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purposes of this multicenter are to determine if brief intervals of highly active antiretroviral therapy (HAART) suspension result in increased HIV-specific CD8 and/or CD4 activity; to determine whether the increase in such activity will result in prolonged suppression of viremia with subsequent suspension of HAART; to determine whether the stimulation of HIV-specific immunity reduces HIV proviral load; and to determine whether cycles of HAART drug holidays of increasing duration result in the emergence of drug-resistant virus or if drug-sensitive virus persists. The rationale is that some HIV-infected patients taking HAART have been able to achieve prolonged suppression of HIV plasma viremia for extended periods of time. However, attempts to discontinue HAART have consistently resulted in the return of HIV in the plasma, suggesting that cell-associated HIV may be a factor. The elimination of cell-associated HIV is dependent on a number of immune-mediated mechanisms, including CD8 cells. Although CD8 cells are frequently detected in individuals with incomplete HIV suppression, it has been noted that both CD8 and CD4 cells are markedly reduced in individuals with prolonged HIV suppression. It is hypothesized that a brief and low-level increase in HIV viremia, resulting from suspension of HAART, might boost HIV-specific CD8 and CD4 T-cells. After the subsequent suppression of viremia with the reintroduction of HAART, the expanded CD8 population might be able to better control viral replication or to eliminate some of the cell-associated HIV. This could result in a more prolonged period of aviremia with a subsequent suspension of HAART.
Showing the most recent 10 out of 470 publications
