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.