Resistance to Anti-HIV Agents for Anti-AIDS Drug Development

San Diego Veterans Affairs Medical Center and University of California San Diego Departments of Pathology & Medicine, 0679, 9500 Gilman Drive, La folia, CA 92093-0679 INTRODUCTION Infection with hum an im m unodeficiency virus is a chronic process with persistent, high rates of replication. The virus has been shown to exhibit high rates of m utation over time within the same individual. It is thus not surprising that drug resistant m utants of HIV were shown to emerge under the selective pressure of prolonged chemotherapy, especially with the knowledge of the clinical emergence of drug resistant m utants of herpes simplex virus, varicella zoster virus, cytomegalovirus, influenza A virus and rhinovirus1. Since the original description of diminished susceptibility of isolates of HIV-1 to AZT (zidovudine)2, the literature has proliferated with descriptions of diminished susceptibility to AZT in different clinical situations, with different assay systems, and of genetic mutations responsible for changes in susceptibility. In addition to AZT these descriptions have been applied to o ther nucleosides and to non-nucleoside antiretroviral drugs. A num ber of critical, practical issues require clarification and rem ain under active investigation. Most prom inent among these issues is the contribution of drug resistance to failure of drug therapy and the prospect of therapeutic strategies to address this problem.