ADVANCES IN PHARMACOTHERAPY - TREATMENT OF HIV-INFECTION

Current estimates indicate that at least one million people in the Uni ted States, 500 000 in Western Europe and perhaps six million individu als in sub-Saharan Africa are infected by the human immunodeficiency v irus (HIV), the virus that causes the acquired immunodeficiency syndro me (AIDS). This article summarizes recent developments in the study an d clinical application of agents directed against HIV. There are prese ntly four primary targets in the life-cycle of HIV for interruption of replication. Of these, only the inhibition of reverse transcriptase b y 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 t herapy. Even so, there is much that remains to be learned about zidovu dine and other dideoxynucleoside agents regarding the clinical meaning of HN-resistance, and the ideal time to initiate therapy. Putative an ti-HIV compounds such as non-nucleoside reverse transcriptase inhibito rs, tat inhibitors and protease inhibitors are currently under investi gation. The development of these compounds, with mechanisms of action different from dideoxynucleosides, represents exciting prospects for c ombination therapy.