Immune reconstitution in HIV-1-infected individuals treated with potent antiretroviral therapy

Potent combination antiretroviral therapy that was introduced in the mid-1990s for treatment of HIV-1 infection has resulted in unprecedented decreases in HIV-1 replication and increases in CD4+ T cell counts in many individuals. Coincident with the introduction of potent combination antiretroviral therapy, substantial declines in AIDS-related morbidity, and mortality have been observed. Although these declines strongly suggest that significant immune reconstitution is occurring, increasing evidence suggests that immune reconstitution is neither uniform nor complete in all treated individuals. Clinical data suggest that some HIV-1-associated malignancies have not declined despite the new therapies, and that not all treated individuals reconstitute CD4+ T cell numbers to normal values. Laboratory studies reveal that immune responses to ubiquitous antigens are reconstituted, but that responses to rarely encountered antigens, such as tetanus, are not reconstituted without repeat vaccination. Many questions remain concerning the extent and clinical significance of the immune reconstitution that occurs in the setting of antiretroviral drug therapy. A better understanding of the nature of the immune reconstitution that results from potent antiretroviral therapy is critical to the optimal clinical management of HIV-1-infected individuals, and may provide important insights into the immunopathogenesis of HIV-1 infection as well.