title: Virological and immunological response in HIV-1-infected patients with multiple treatment failures receiving raltegravir and optimized background therapy, ANRS CO3 Aquitaine Cohort.
abstract: BACKGROUND
  The efficacy of raltegravir plus optimized background therapy (OBT) has been demonstrated for antiretroviral (ARV)-experienced HIV-1-infected patients in randomized clinical trials. We studied viro-immunological response, pharmacokinetic parameters and genotypic test results in an observational cohort of multiple ARV class-experienced patients starting a raltegravir-based regimen.
  
  
  METHODS
  Already enrolled ANRS CO3 Aquitaine Cohort patients with virological failure were included in this study after starting a raltegravir-based regimen (400 mg twice a day, week 0). Virological success was defined by the plasma HIV-1 RNA level [viral load (VL)] <2.7 log(10) copies/mL at week 12 and <1.7 log(10) copies/mL at week 24. One patient was excluded from further analysis (no follow-up after week 4).
  
  
  RESULTS
  Fifty-one patients [male/female = 43/8, median age = 48 (interquartile range = 43, 55) years] were included. At week 0, median CD4 count was 244 (110; 310)/mm(3) and median VL was 4.2 (3.6, 4.7) log(10) copies/mL. At week 24, 39 (78%) patients experienced virological success: 4 (44%), 14 (82%) and 21 (87%) patients with a genotypic sensitivity score <1, > or =1 and <2 and > or =2 (P = 0.02), respectively. Raltegravir-related mutations emerged in 9 of 11 failing patients (82%): Q148H/R (n = 5), N155S/H (n = 3) and S230N (n = 1). Median CD4 increases from week 0 to week 4 and week 24 were 28 (-4, 85) and 57 (0, 156) cells/mm(3), respectively. A poor immune response was independently associated with a lower VL decline (week 0 to week 12) [odds ratio (OR): 3.5, 95% confidence interval (CI): 1.4, 8.4, for 1 log(10) less] and CD4+% at baseline (OR: 2.6, 95% CI: 0.97, 8.3, for 10% lower).
  
  
  CONCLUSIONS
  Raltegravir plus OBT provided a good virological success rate in highly pre-treated patients under clinical routine conditions.
authors.affiliation: Inserm, Unit Epidemiology and Biostatistics, Bordeaux, France. Linda.Wittkop@isped.u-bordeaux2.fr
authors.forename: Linda
authors.initials: L
authors.lastname: Wittkop
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.forename: Daniel
authors.initials: D
authors.lastname: Da Silva
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.forename: Patrick
authors.initials: P
authors.lastname: Mercié
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raymond
authors.forename: Guerric
authors.initials: G
authors.lastname: Anies
authors.forename: Hervé
authors.initials: H
authors.lastname: Fleury
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Saux
authors.forename: Francois
authors.initials: F
authors.lastname: Dabis
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellegrin