N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations

AIDS. 2010 Jan 16;24(2):317-9. doi: 10.1097/QAD.0b013e3283315697.

Abstract

We previously demonstrated that N348I in HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, both of these inhibitors are currently infrequently used in developed countries, and the impact of N348I on newer reverse transcriptase inhibitors, such as tenofovir and etravirine, is unknown. In this study, we demonstrate that N348I alone confers no resistance to tenofovir and low-level resistance to etravirine. However, N348I significantly decreases tenofovir susceptibility when combined with thymidine analogue mutations and etravirine susceptibility when combined with Y181C.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Drug Resistance, Multiple, Viral / genetics*
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Mutagenesis, Site-Directed / methods
  • Mutation / genetics*
  • Nitriles
  • Organophosphonates / therapeutic use
  • Pyridazines / therapeutic use
  • Pyrimidines
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Tenofovir

Substances

  • Nitriles
  • Organophosphonates
  • Pyridazines
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • etravirine
  • Tenofovir
  • HIV Reverse Transcriptase
  • Adenine