HIV-1 Drug Resistance Mutations: an Updated Framework for the Second Decade of HAART

More than 200 mutations are associated with antiretroviral resistance to drugs belonging to six licensedantiretroviral classes. More than 50 reverse transcriptase mutations are associated with nucleosidereverse transcriptase inhibitor resistance including M184V, thymidine analog mutations, mutationsassociated with non-thymidine analog containing regimens, multi-nucleoside resistance mutations, andseveral recently identified accessory mutations. More than 40 reverse transcriptase mutations areassociated with nonnucleoside reverse transcriptase inhibitor resistance including major primaryand secondary mutations, non-polymorphic minor mutations, and polymorphic accessory mutations.More than 60 mutations are associated with protease inhibitor resistance including major protease,accessory protease, and protease cleavage site mutations. More than 30 integrase mutations areassociated with the licensed integrase inhibitor raltegravir and the investigational inhibitor elvitegravir.More than 15 gp41 mutations are associated with the fusion inhibitor enfuvirtide. CCR5 inhibitorresistance results from mutations that promote gp120 binding to an inhibitor-bound CCR5 receptor orCXCR4 tropism; however, the genotypic correlates of these processes are not yet well characterized.