Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children

J Antimicrob Chemother. 2013 Oct;68(10):2344-8. doi: 10.1093/jac/dkt198. Epub 2013 Jun 3.

Abstract

Background: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe).

Methods: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe.

Results: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe.

Conclusions: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.

Keywords: Hispanics; cumulative HIV RNA; therapy adherence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Resistance, Viral*
  • Female
  • HIV / drug effects*
  • HIV / genetics
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Male
  • Mutation, Missense
  • Nitriles
  • Prevalence
  • Pyridazines / administration & dosage*
  • Pyridazines / pharmacology*
  • Pyrimidines
  • Retrospective Studies
  • Risk Factors

Substances

  • Anti-HIV Agents
  • Nitriles
  • Pyridazines
  • Pyrimidines
  • etravirine