Nonnucleoside Reverse Transcriptase Inhibitors

The nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a structurally and chemically dissimilar group of antiretrovirals that are potent and highly selective inhibitors of HIV-1 reverse transcriptase. Other retroviral reverse transcriptase enzymes, such as HIV-2, hepatitis viruses, herpes viruses, and mammalian enzyme systems, are unaffected by these compounds. Unlike the nucleoside analogs, the NNRTIs interfere with HIV-1 reverse transcriptase by noncompetitively binding directly to the enzyme downstream from the active catalytic site. The compounds are active in their native state, requiring no phosphorylation or other activity-dependent alteration. They are extensively metabolized in the liver; very little drug is excreted uncha…