Prevalence of etravirine (ETR)-RAMs at NNRTI failure and predictors of resistance to ETR in a large Italian resistance database (ARCA)

Clin Microbiol Infect. 2013 Oct;19(10):E443-6. doi: 10.1111/1469-0691.12229. Epub 2013 Apr 26.

Abstract

The prevalence of drug resistance associated with the failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and the predictors of resistance to Etravirine (ETR) were assessed in 2854 subjects: 39 < 18 (paediatric) and 2815 ≥ 18 (adult) years old. These subjects failed to respond to their current NNRTI treatment, were three-class experienced and had been exposed to NNRTI for ≥3 months. A total of 1827 adult (64.9%) and 32 paediatric subjects (82.1%) harboured the virus with at least one ETR mutation. V179I, Y181C and G190A were the most frequent mutations in both groups. A significantly increased risk of ETR resistance with all three algorithms (Monogram (MGR) >3, Tibotec (TBT) >2 and enhanced MGR (ENH) ≥4) emerged in the paediatric population. Multivariate analysis revealed an increased risk of developing TBT >2 for NNRTI exposure, ENH ≥4 for NNRTI and EFV exposure in paediatric subjects; NVP exposure and higher (≥3.5 log10) HIV-RNA values for all three algorithms in adult subjects, whereas CD4 ≥ 200/μL appeared to be protective. The risk of being ETR resistant was more than doubled for paediatric vs. adult subjects, probably due to a more extensive use of NNRTI and an incomplete virological control.

Keywords: Drug resistance; HIV-1; etravirine; genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Drug Resistance, Viral
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification*
  • Humans
  • Italy / epidemiology
  • Male
  • Multivariate Analysis
  • Nitriles
  • Prevalence
  • Pyridazines / therapeutic use*
  • Pyrimidines
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Failure

Substances

  • Nitriles
  • Pyridazines
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • etravirine