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, and provide the rationale for concerted efforts to understand the host immune response to the virus and to develop new strategies to combat the infection with immune based therapies. Historically, the greatest hole in the immune repertoire in HIV-1 infection has been the lack of strong virus-specific proliferative responses. However, new 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 antiviral therapy in the earliest stages of acute HIV-1 infection have led to persistent, strong HIV-1-specific T-helper cell responses, analogous to those seen in persons who are able to control viremia in the absence of antiviral therapy. We hypothesize 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.