MHC class II genotype and the control of viremia in HIV-1-infected individuals on highly active antiretroviral therapy.

Abstract

HIV-1 infection sets up a complex dynamic equilibrium between viral replication and the HIV-1–specific immune response. In the absence of antiretroviral therapy, the high rate of viral replication, the associated depletion of CD4+ T cells, and the high mutation rate of the virus combine to eventually overwhelm the immune system. In certain cases, however, it appears that the immune system has the upper hand, and viral replication occurs at only very low levels. Two groups of individuals fall into this category: some long-term nonprogressors (LTNPs) who have either very low or undetectable levels of plasma virus (1–3), and patients who are treated with highly active antiretroviral therapy (HAART) shortly after seroconversion who subsequently discontinue therapy (4, 5). Much recent effort has been directed toward studying the HIV-specific immune response of these subjects in the hope of finding clues that will be helpful in designing vaccines. Viral antigen-specific CD4+ and CD8+ T cells play an important role in HIV-specific immunity. The receptors on these cells recognize processed viral peptides that are presented by MHC molecules on the surfaces of antigen presenting cells. While considerable progress has been made regarding the mechanism by which responding T cells control viral replication, less is known about the role of the MHC genotype in patients who spontaneously control viremia.