Do any drug resistance mutations reduce susceptibility to drugs belonging to more than one drug class?
The NRTIs and NNRTIs inhibit the same HIV-1 protein – the RT enzyme. In contrast, the PIs inhibit the protease enzyme, the INIs inhibit the integrase enzyme, the fusion inhibitors inhibit the gp41 transmembrane envelope (Env) protein, and the CCR5 inhibitors disrupt the mechanism by which the gp120 surface Env protein binds to CCR5. Even though the NRTIs and NNRTIs inhibit the same protein, there is surprisingly little evidence for cross-resistance between these drug classes (i.e. mutations that reduce susceptibility to one or more drugs of each drug class). In fact, several mutations that reduce NRTI susceptibility increase NNRTI susceptibility and several mutations that reduce NNRTI susceptibility increase NRTI susceptibility. This “antagonism” between many NRTI and NNRTI resistance mutations may be responsible from the “synergism” of NRTI and NNRTI drug combinations. However, in the past 2-3 years, several RT mutations have been identified that are associated with both NRTI and NNRT
