Management of antiretroviral drug therapy in human immunodeficiency virus infection.

Nucleoside analog reverse transcriptase inhibitors, including zidovudine, didanosine, and zalcitabine, remain the cornerstone of therapy against human immunodeficiency virus (HIV) infection, the cause of AIDS. Although therapeutic regimens have been designed that are effective in slowing the progression of disease, therapy with these agents has not been optimized. Ultimately, therapy is destined to fail in most patients. Decisions regarding when to begin therapy and the course of action to take when failure of therapy occurs are largely in the hands of the patient's physician, and currently must be made without the support of conclusive clinical data. In addition to an understanding of the recommended dosing guidelines, proper management of AIDS therapy requires a fundamental knowledge of the disease process, the pharmacology and limitations of the agents employed against the virus, and close cooperation with the clinical laboratory. Therefore, this article reviews the pharmacology of the three drugs currently approved for treatment of HIV infection, and the current guidelines for their use. The article also reviews the clinical and laboratory management of these agents, including the use of surrogate markers and the potential for pharmacokinetic optimization of therapy.