title: Prevalence of etravirine (ETR)-RAMs at NNRTI failure and predictors of resistance to ETR in a large Italian resistance database (ARCA).
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.
authors.affiliation: Divisione Clinicizzata di Malattie Infettive, Dipartimento di Scienze Biomediche e Cliniche 'Luigi Sacco', Universita' degli Studi di Milano, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Rusconi
authors.forename: F
authors.initials: F
authors.lastname: Adorni
authors.forename: B
authors.initials: B
authors.lastname: Bruzzone
authors.forename: A
authors.initials: A
authors.lastname: Di Biagio
authors.forename: G
authors.initials: G
authors.lastname: Meini
authors.forename: A
authors.initials: A
authors.lastname: Callegaro
authors.forename: G
authors.initials: G
authors.lastname: Punzi
authors.forename: E
authors.initials: E
authors.lastname: Boeri
authors.forename: M
authors.initials: M
authors.lastname: Pecorari
authors.forename: L
authors.initials: L
authors.lastname: Monno
authors.forename: N
authors.initials: N
authors.lastname: Gianotti
authors.forename: L
authors.initials: L
authors.lastname: Butini
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.forename: E
authors.initials: E
authors.lastname: Polilli
authors.forename: M
authors.initials: M
authors.lastname: Galli
mesh_terms: D000328:Adult; D002648:Child; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D015999:Multivariate Analysis; D009570:Nitriles; D015995:Prevalence; D011724:Pyridazines / Q000627:therapeutic use*; D011743:Pyrimidines; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine
keywords: Drug resistance; HIV-1; etravirine; genotype