THE GENETIC AND FUNCTIONAL BASIS OF HIV-1 RESISTANCE TO NONNUCLEOSIDEREVERSE-TRANSCRIPTASE INHIBITORS

The nonnucleoside reverse transcriptase (RT) inhibitors are structural ly diverse compounds that are specific inhibitors of the human immunod eficiency virus type 1 RT enzyme. The compounds are largely functional ly identical and bind to a common site in the enzyme. HIV-1 variants t hat exhibit reduced susceptibility to these inhibitors have been deriv ed in cell culture and, more recently, from HIV-1-infected patients un dergoing experimental therapy. The variants express amino acid substit utions at RT positions that apparently interact directly with the inhi bitors. Effects of specific substitutions at these positions vary amon g the compounds, suggesting subtle differences in how the compounds ph ysically interact with the enzyme.