HIV-1 infection is associated with progressive and relentless destruction of the immune system in the majority of infected persons, but some persons appear to be able to successfully contain the virus in the absence of antiviral therapy. Such cases suggest that the host immune response can successfully contain the virus. Historically, the greatest hole in the immune repertoire has been the lack of strong virus-specific proliferative responses. However, some studies have identified a potent Th cell response in some infected persons, and have shown a statistically significant negative correlation between plasma viremia and virus-specific CD4 T helper cells directed at the p24 protein. Moreover, early institution of potent Th cell response in some infected persons, and have shown a statistically significant negative correlation between plasma viremia and virus-specific CD4 T helper cells directed at the p24 protein. Moreover, early institution of potent antiviral therapy in the earliest stages of acute HIV-1 infection have led to strong p24-specific and gp 160-specific Th cell responses, analogous to those seen in persons who are able to control viremia in the absence of antiviral therapy. The PI hypothesizes that this is because potent antiviral therapy is able to protect virus-specific Th cells as they become activated, and thus these cells are not lost in the earliest stages of infection. The purpose of this proposal is to perform a detailed characterization of the cellular immune response to HIV-1 in a unique cohort of persons treated during primary infection, and to determine the effects of early therapy on HIV-1 -specific CTL, Th cells and antibody responses. The hypothesis to be tested in this proposal is that control of viremia is associated with strong Th, CTL and antibody responses to HIV-1, and that restoration of effective immunity by early intervention with potent antiviral therapy will allow for the generation of virus-specific immune responses that will contain viremia after discontinuation of antiviral therapy. These studies will include determining the breadth, magnitude and specificity of virus specific of virus specific immune responses following treatment of acute HIV-1 infection, using new techniques including ELISPOT assays and HLA-peptide tetramers which allow for the enhanced detection and quantitation of these responses. In addition, the team will determine the effects of interruption of therapy in persons with treated acute infection who have immune responses to HIV that are similar to those with long-term non-progressing infection. Specifically they propose to a) identify, recruit and characterize persons with acute HIV-1 infection, and establish a specimen bank b) determine the breadth, magnitude and specificity of CTL in treated acute and early HIV-1 infection c.) determine the breadth, magnitude and specificity of HIV-1-specific T helper cell responses in treated acute HIV-1 infection; and d.) to determine the effects of interruption of antiviral therapy on the virus-specific immune responses to HIV-1 in persons with treated acute HIV-1 infection who develop strong virus specific immune response.
