New antiretroviral agents in clinical development

As we expand our understanding of the biology of the human immunodeficiency virus, we generate an increasing directory of potential antiretroviral therapies. Despite this increase, the number of promising new agents entering clinical trials is limited by unexpected toxicity, lower than anticipated activity, resistance, or problems with drug disposition or manufacture. In the past year, it seems that more antiretroviral agents have met with failure than with success. Nonetheless, the increasing sophistication of applied science in this field, and the continued availability of novel agents for clinical study, provide encouragement. Three major trends have emerged: 1) the continuing predominance of nucleoside analogues that inhibit the viral reverse transcriptase, despite their toxicities and limited clinical benefit; 2) the increasing importance of drug resistance in governing the use of available agents and in guiding the development of new classes of drugs; and 3) the accelerated licensure of promising new drugs for acquired immunodeficiency syndrome, exemplified by the approval of didanosine (dideoxyinosine) and zalcitabine (dideoxycytidine).