Which mutations cause the resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in antiretroviral therapy of HIV infection?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

Answer

Mutations within the reverse transcriptase gene domain alter the ability of the NNRTIs to bind the enzyme. First-generation NNRTIs have a low genetic barrier to resistance, whereby a single mutation in the binding site can decrease the ability of the drug to bind, significantly diminishing activity. [30] First-generation NNRTI resistance has been associated with mutations at multiple codons; however, the presence of either a K103N or Y181C mutation is sufficient to cause clinical failure of delavirdine, efavirenz, and nevirapine. [30]

Associated mutations include the following [30] :

  • Delavirdine - A98G, L100I, K101E, K103N, K103T, V179D, Y181C, Y188L, M230L, P236L, Y318F

  • Efavirenz - L100I, K101E, K103N, V108I, V179D, Y181C, Y188L, G190S, M230L

  • Nevirapine - A98G, L100I, K101E, K103N, V106A, V106I, V108I, Y181C, Y191I, Y188C, Y188H, G190A, P225H, M230L, P236L, Y318W


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