Controversies in anti-retroviral therapy of adults

Much controversy surrounds the use of antiretroviral drugs in HIV-infected patients. The many studies involving large numbers of patients that have been and are being conducted have raised as many questions as they have sought to answer. Given that no cure exists and that all clinically available drugs have only limited activity despite their high toxicity, the question of which drug (or combination of drugs) to use, and in whom, continues to vex both the clinician and the patient. Only three specific antiretroviral agents are currently licensed for use: zidovudine (ZDV), didanosine (dideoxyinosine, ddI) and zalcitabine (dideoxycytidine, ddC). This article reviews the major studies comparing the clinical efficacy of these drugs and the possible benefits of adding acyclovir to zidovudine therapy. The questions of when to begin antiretroviral therapy and the role of combination chemotherapy are discussed. Whenever possible, 'clinical' endpoints (death or clinical progression) are distinguished from 'softer' endpoints (surrogate markers of progression, such as the CD4 lymphocyte count) in the studies reviewed. Recommendations for the use of antiretroviral agents based on currently available published data are made.