title: A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial.
abstract: OBJECTIVE
  To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure.
  
  
  METHODS
  Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks.
  
  
  RESULTS
  One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9).
  
  
  CONCLUSIONS
  In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.
authors.affiliation: MRC Clinical Trials Unit, London, UK. hannah.green@ctu.mrc.ac.uk
authors.forename: Hannah
authors.initials: H
authors.lastname: Green
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Alexandra
authors.initials: A
authors.lastname: Compagnucci
authors.forename: Vania
authors.initials: V
authors.lastname: Giacomet
authors.forename: Anita
authors.initials: A
authors.lastname: de Rossi
authors.forename: Lynda
authors.initials: L
authors.lastname: Harper
authors.forename: Yacine
authors.initials: Y
authors.lastname: Saïdi
authors.forename: Guido
authors.initials: G
authors.lastname: Castelli-Gattinara
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Babiker
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.forename: Hermione
authors.initials: H
authors.lastname: Lyall
authors.forename: Lee T
authors.initials: LT
authors.lastname: Bacheler
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rosso
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Marinella
authors.initials: M
authors.lastname: Della Negra
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D013045:Species Specificity; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents