The impact of highly active antiretroviral therapy on HIV-specific immune function

Highly active antiretroviral therapy (HAART) can suppress HIV type 1 plasma viremia to undetectable levels for up to 3 years or more. When the therapy is discontinued, viral rebound occurs in a majority of patients, indicating that HAART is unable to completely eradicate the virus. Initial calculations of the half-lives of the infected cells (estimated to be 14-21 days) suggested that only 3 years continuous HAART therapy would be necessary to achieve complete eradication; however, several studies have determined that the half-lives of chronically infected cells are in the order of 6-44 months. New estimates indicate that it may take as long as 60 years to eradicate the virus. Thus, there has been movement toward combining HAART with various means of augmenting and/or reconstituting the host's immune system, especially HIV-1-specific immune responses. The long-term goal is to discontinue HAART and permit the reconstituted immune system to contain whatever small amounts of the virus remain.