Antiretroviral Drug Resistance: Mechanisms, Pathogenesis, Clinical Significance

Publisher Website
Google Scholar
Abstract
Since HIV drug resistance was first recognized, many studies have documented the emergence of isolates with reduced susceptibility under the selective pressure of drug therapy, both in vitro and in vivo. These resistant isolates have been identified for nucleosides, non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Resistant isolates have been characterized with regard to cross resistance to other drugs, enzymatic activity of the target protein, mutations in the target gene and protein, and the relationship of these mutations to the x-ray crystallographic structure of the enzyme. Many of these aspects of HIV drug resistance were reviewed in some detail in the preceding symposium proceedings.’ I shall briefly summarize the status of the in vitro data with reverse transcriptase inhibitors before concentrating upon more recent developments in the field relating to resistance to protease inhibitors, the interrelationships of pathogenesis and drug resistance, and the clinical significance of drug resistance.