title: Efficacy, tolerability and virological consequences of long-term use of unboosted atazanavir plus 2 NRTIs in HIV-infected patients.
abstract: OBJECTIVE
  Switch to unboosted atazanavir (ATV) is an attractive option due to convenience and tolerability in HIV-positive patients. With limited available data we investigated the determinants of long-term efficacy and the consequences of virological failure of unboosted atazanavir-based regimens.
  
  
  METHODS
  Retrospective analysis in two Italian large outpatient clinics including demographic, immunovirological, resistance and pharmacokinetic data.
  
  
  RESULTS
  249 patients receiving atazanavir (400 mg once-daily) plus 2 NRTIs were included; 163 were males (65.5%) and median age was 47 years (42-51.5). Median CD4+ T-cell count was 396/uL (261-583); 146 (58.6%) presented a viral load < 50 copies/mL. Over a median follow up of 157 weeks (106-203) 193 patients (77.5%) were still on treatment with 10 (4%) and 2 (0.8%) stopping for virological failure or toxicity, respectively. Ten patients with virological failure presented newly selected resistance associated mutations (RAMs) for NRTIs (2/10) or ATV (4/10, one I50L). Total cholesterol and triglycerides showed significant decreases at 48 [-4 mg/dL and -41 mg/dL] and 96 weeks [-14 mg/dL and -54 mg/dL] as compared to baseline. At multivariate analysis a genotypic sensitivity score ≤ 1, atazanavir RAMs > 1 and suboptimal adherence were independently associated with virological failure; in lamivudine/emtricitabine-treated patients the presence of M184V (without other NRTI RAMs) was not associated with virological failure.
  
  
  CONCLUSIONS
  Unboosted-atazanavir containing regimens were efficacious (with uncommon virological failures) and well-tolerated (with improvements in lipid profile over time) treatments in HIV-positive patients. Isolated M184V in lamivudine/emtricitabine recipients was not associated with higher failure rates supporting the use of functional ATV-based dual therapies as maintenance strategies.
authors.forename: S
authors.initials: S
authors.lastname: Bonora
authors.forename: A
authors.initials: A
authors.lastname: Calcagno
authors.forename: O
authors.initials: O
authors.lastname: Vigano
authors.forename: P
authors.initials: P
authors.lastname: Bigliano
authors.forename: L
authors.initials: L
authors.lastname: Marinaro
authors.forename: E
authors.initials: E
authors.lastname: Colella
authors.forename: G
authors.initials: G
authors.lastname: Orofino
authors.forename: L
authors.initials: L
authors.lastname: Trentini
authors.forename: M C
authors.initials: MC
authors.lastname: Tettoni
authors.forename: A
authors.initials: A
authors.lastname: D'Avolio
authors.forename: S
authors.initials: S
authors.lastname: Mercadante
authors.forename: M
authors.initials: M
authors.lastname: Galli
authors.forename: G
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Ospedale Amedeo di Savoia, Clinica Universitaria I Piano, C.so Svizzera 164, 10159, Torino, Italy. stefano.bonora@unito.it.
authors.forename: S
authors.initials: S
authors.lastname: Rusconi
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate