Effect of mutations at position E138 in HIV-1 reverse transcriptase on phenotypic susceptibility and virologic response to etravirine

J Acquir Immune Defic Syndr. 2011 Sep 1;58(1):18-22. doi: 10.1097/QAI.0b013e3182237f74.

Abstract

The contribution of E138 mutations to etravirine resistance was investigated. Amino acids at position E138 after failure with etravirine in DUET were A (n = 1), G (n = 5), K (n = 3), P (n = 1), Q (n = 5), and V (n = 2). At baseline, only E138A and Q were found at 3.0% and 2.5%, respectively. Virologic response (less than 50 copies/mL) was observed in six of 12 and eight of 10 patients with E138A and E138Q, respectively. Site-directed mutants harboring E138A/G/K/Q/R or S showed etravirine fold change values of 2.9, 2.4, 2.6, 3.0, 3.6, and 2.8, respectively. E138G, K, and Q were added to the existing etravirine-weighted genotypic score including 17 etravirine resistance-associated mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / pharmacology*
  • Drug Resistance, Viral / genetics
  • Gene Expression Regulation, Viral
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Mutation
  • Nitriles
  • Phenotype
  • Pyridazines / pharmacology*
  • Pyrimidines

Substances

  • Anti-HIV Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • etravirine
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase