title: Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study.
abstract: We assessed etravirine resistance in treatment-experienced, HIV-1-infected children (n=41)/adolescents (n=60) who received twice-daily etravirine 5.2 mg/kg and a background regimen (boosted protease inhibitor plus nucleoside/nucleotide reverse transcriptase inhibitors, optional enfuvirtide/raltegravir) in a Phase II, open-label, multicentre trial (PIANO).
  
  
  
  In addition to phenotypes, viral genotypes were assessed by population and deep sequencing (PS and DS) in virological failures (VFs; baseline and end point) and responders (baseline). Minority resistance-associated mutations (RAMs) were defined as those with frequencies above 1% and not detected with PS.
  
  
  
  By week 48, 41/101 (40.6%) patients experienced VF; 17/41 (41.5%) VFs and 22/54 (40.8%) responders had ≥1 baseline etravirine RAM by PS, mainly A98G, K101E, V106I and G190A. Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]). The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (≥3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3). In 15 of 29 (51.7%) VFs with baseline DS/PS and end point PS data, ≥1 emerging etravirine RAM was detected by PS, which was not detected at baseline by DS in most cases (12/15 [80.0%]). In 10/26 (38.5%) VFs with baseline/end point DS data, ≥1 additional emerging minority etravirine RAM was detected.
  
  
  
  Patterns of etravirine resistance in adults, adolescents and children experiencing VF are similar. The presence of minority etravirine RAMs at baseline was not consistently associated with treatment failure. ClinicalTrials.gov: NCT00665847.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. ltambuyz@its.jnj.com.
authors.forename: Lotke
authors.initials: L
authors.lastname: Tambuyzer
authors.forename: Kim
authors.initials: K
authors.lastname: Thys
authors.forename: Annemie
authors.initials: A
authors.lastname: Hoogstoel
authors.forename: Steven
authors.initials: S
authors.lastname: Nijs
authors.forename: Frank
authors.initials: F
authors.lastname: Tomaka
authors.forename: Magda
authors.initials: M
authors.lastname: Opsomer
authors.forename: Sandra
authors.initials: S
authors.lastname: De Meyer
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D024882:Drug Resistance, Viral / Q000235:genetics*; D019143:Evolution, Molecular; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D017211:Treatment Failure
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine