title: Efficacy and safety of switching to raltegravir plus atazanavir dual therapy in pretreated HIV-1-infected patients over 144 weeks: a cohort study.
abstract: BACKGROUND
  To decrease drug burden among HIV-1-positive adults, we need a new gold standard for antiretroviral therapy maintenance strategies.
  
  
  METHODS
  This retrospective study aimed to assess efficacy in maintenance strategy of atazanavir (ATV) and raltegravir (RAL) dual therapy. The proportion of patients with HIV-1 RNA < 40 copies/ml at specific time points was recorded. Immunological response, safety, and pharmacokinetics were assessed.
  
  
  RESULTS
  Overall, 39 patients were switched to a RAL/ATV (n = 32) or RAL/ATV plus ritonavir (n = 7) regimen. Almost all patients (95%) received RAL twice daily. Most patients (70%) received a 400 mg ATV dosing per day, once (26%) or twice daily (44%). The percentages of virological success at weeks 24, 48, 96, and 144 were 92% (95% confidence interval (CI), 83-10), 86% (95% CI, 74-98), 70% (95% CI, 52-88), and 63% (95% CI, 42-84), respectively. Overall, 12 (31%) patients stopped dual therapy: 7 patients because of adverse events, mostly clinical myositis (n = 3). Confirmed virological failure occurred in three patients; two of them developed RAL resistance patterns. A significant increase in the CD4+/CD8 + T-cell ratio was observed at week 48 (p < 0.005). Only grade 1-2 adverse events were observed. Trough plasma levels presented a wide variability. Suggested trough concentrations were achieved in 79% and 94% of patients for ATV and RAL, respectively. An unboosted 400 mg per day ATV dosing seemed to be appropriate, regarding the targeted levels achieved and the lack of grade 3 or 4 hyperbilirubinemia.
  
  
  CONCLUSIONS
  We demonstrated, on a 3-year follow-up, the efficacy and safety of RAL plus ATV maintenance dual therapy.
authors.affiliation: From the Le Trait d'Union, Centre de Soins de l'Infection par le VIH, Hôpitaux Universitaires de Strasbourg , Strasbourg , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Gantner
authors.forename: Christine
authors.initials: C
authors.lastname: Koeppel
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Partisani
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Batard
authors.forename: Claudine
authors.initials: C
authors.lastname: Bernard-Henry
authors.forename: Christine
authors.initials: C
authors.lastname: Cheneau
authors.forename: Erik
authors.initials: E
authors.lastname: De Mautort
authors.forename: Michele
authors.initials: M
authors.lastname: Priester
authors.forename: Patrice
authors.initials: P
authors.lastname: Muret
authors.forename: Charlotte
authors.initials: C
authors.lastname: Sueur
authors.forename: Samira
authors.initials: S
authors.lastname: Fafi-Kremer
authors.forename: David
authors.initials: D
authors.lastname: Rey
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068898:Raltegravir Potassium; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D019438:Ritonavir
keywords: Antiretroviral therapy; dual therapy; long-term efficacy; nucleoside-sparing regimen; switch