Current estimates indicate that at least one million people in the United States, 500 000 in Western Europe and perhaps six million individuals in sub-Saharan Africa are infected by the human immunodeficiency virus (HIV), the virus that causes the acquired immunodeficiency syndrome (AIDS). This article summarizes recent developments in the study and clinical application of agents directed against HIV. There are presently four primary targets in the life-cycle of HIV for interruption of replication. Of these, only the inhibition of reverse transcriptase by drugs such as zidovudine, didanosine and zalcitabine has been shown to be clinically beneficial. Zidovudine is the drug with which we have the greatest experience, and it remains the cornerstone of anti-HIV therapy. Even so, there is much that remains to be learned about zidovudine and other dideoxynucleoside agents regarding the clinical meaning of HN-resistance, and the ideal time to initiate therapy. Putative anti-HIV compounds such as non-nucleoside reverse transcriptase inhibitors, tat inhibitors and protease inhibitors are currently under investigation. The development of these compounds, with mechanisms of action different from dideoxynucleosides, represents exciting prospects for combination therapy.
