a conformational change in the reverse transcriptase that distorts the positioning of the residues that bind DNA, inhibiting polymerization. Mutations in response to NNRTIs decrease the binding of the drug to this pocket. Treatment with a regimen including efavirenz (EFV) and nevirapine (NVP) typically results in mutations L100I, Y181C/I, K103N, V106A/M, V108I, Y188C/H/L and G190A/S. There are three main mechanisms of NNRTI resistance. In the first NRTI mutations disrupt specific contacts between the inhibitor and the NNRTI binding pocket. An example of this is K103N and K101E which sit at the entrance of the pocket, blocking the entrance/binding of the drug. A second mechanism is the disruption of important interactions on the inside of the pocket. For example, Y181C and Y188L result in the loss of important aromatic rings involved in NNRTI binding. The third type of mutations result in changes in the overall conformation or the size of the NNRTI binding pocket. An example is G190E, which creates a steric bulk in the pocket, leaving little or no room for an NNRTI to tightly bind. See also Discovery and development of non-nucleoside reverse-transcriptase inhibitors Protease inhibitors Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors References External links