title: Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.
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.
authors.affiliation: Division of Paediatric Infectious Diseases, Department of Paediatrics, Medical School, UTHealth, 6431 Fannin Street MSB 3.020, Houston, TX 77030, USA.
authors.forename: German A
authors.initials: GA
authors.lastname: Contreras
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Bell
authors.forename: Gabriela P
authors.initials: GP
authors.lastname: Del Bianco
authors.forename: Norma
authors.initials: N
authors.lastname: Pérez
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Kleinosky
authors.forename: James R
authors.initials: JR
authors.lastname: Murphy
authors.forename: Gloria P
authors.initials: GP
authors.lastname: Heresi
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009570:Nitriles; D015995:Prevalence; D011724:Pyridazines / Q000008:administration & dosage* / Q000494:pharmacology*; D011743:Pyrimidines; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine
keywords: Hispanics; cumulative HIV RNA; therapy adherence