Antiretroviral Drug Resistance in HIV-1

Progress in understanding antiretroviral resistance has evolved rapidly in recent years. Specific resistance mutations have been associated with virologic failure of different nucleoside reverse transcriptase inhibitors (NRTIs). These mutations vary in the extent of cross resistance they confer to other drugs in the same class. In addition, two novel mutational patterns conferring resistance to multiple NRTIs have been recognized. Considerable class-specific cross resistance also exists among viruses with reduced susceptibility to nonnucleoside reverse transcriptase inhibitors (NNRTIs). Among protease inhibitors, low level resistance that arises early during virologic failure may be drug specific in some situations, but high level resistance seen later during suboptimal therapy is likely to confer cross resistance to the entire class. Prevalence of drug resistance in infected patients appears to be considerable, and transmission of multidrug-resistant virus has been documented. Current methods of testing for resistance are promising, but they have significant limitations and require further clinical validation. The best approach to prevent resistance is to start treatment early during infection with a regimen that engenders good compliance and is potent enough to decrease viral load to below detection limits of the most sensitive assay available. Once resistance arises, salvage regimens in general have compromised efficacy and should be planned with attention to the patient's prior drug treatment history and the viruses' suspected or demonstrated resistance patterns.