Longer-term immunologic effects and side effects of successful antiretroviral therapy

With the development of more potent and better tolerated antiretroviral regimens, durable antiviral responses are being observed in an increasing fraction of patients. Substantial benefits are associated with these responses: Initially memory, then naive, CD4 cell counts may rise by 150-200 cells/mm(3); CD8 cell numbers also rise sharply but then fall below pretreatment levels, presumably as antigenic stimuli driving the CD8 response decline; cellular activation markers decline; distortions in the T cell repertoire gradually lessen; and increases in proliferative responses to mitogens and recall antigens are more easily elicited. Clinical benefits directly accompany these immunologic benefits. Other than peripheral neuropathy, few long-term toxicities are associated with nucleoside analogue reverse transcriptase inhibitors. Recent reports, however, link protease inhibitors with hyperlipidemia, redistribution of body fat, and diabetes mellitus. As more human immunodeficiency virus type 1-infected persons receive long-term antiviral maintenance therapy, successful management of these toxicities will require more attention.