Mid-dosing interval concentration of atazanavir and virological outcome in patients treated for HIV-1 infection.

Massimiliano Fabbiani, Simona Di Giambenedetto, Enzo Ragazzoni, Manuela Colafigli, Maria Letizia Prosperini, Roberto Cauda, Pierluigi Navarra, Andrea De Luca

Risultato della ricerca: Contributo in rivistaArticolo in rivista

17 Citazioni (Scopus)


OBJECTIVES: We investigated the clinical significance of monitoring the mid-dosing interval atazanavir (ATV) concentration (measured 12 +/- 2 h after intake; C(12 h)) in patients taking this drug once daily in the evening. METHODS: We retrospectively selected HIV-infected patients harbouring ATV-susceptible virus who underwent therapeutic drug monitoring (TDM) of ATV C(12 h) during routine out-patient visits, and we correlated C(12 h) to the 24-week virological response and toxicity. RESULTS: A total of 115 plasma samples from 86 patients (76.7% with baseline HIV RNA<50 HIV-1 RNA copies/mL) were analysed. ATV plasma concentrations showed high inter-individual variability. ATV plasma levels were higher in samples obtained from patients taking boosted regimens (P<0.001) and not concomitantly receiving acid-reducing agents (P=0.007). In a multivariate model, ritonavir boosting, use of acid-reducing agents and liver cirrhosis showed an independent association with ATV level. Virological response at 24 weeks was observed for 94 of the 115 samples (81.7%). We identified a concentration cut-off of 0.23 mg/L which predicted virological response at 24 weeks: samples with a C(12 h)< or =0.23 mg/L showed virological failure in 41.2% of cases, whereas samples with a C(12 h)>0.23 mg/L showed virological failure in 14.3% of cases (P=0.021). In multivariate analysis, C(12 h)>0.23 mg/L was an independent predictor of virological response [odds ratio (OR) 4.23, P=0.031]. ATV levels correlated with concomitant unconjugated bilirubin levels (r=0.223, P=0.037), but a concentration cut-off predictive of moderate/severe hyperbilirubinaemia could not be identified. CONCLUSIONS: We identified a C(12 h) efficacy threshold that predicted virological response; this could be useful for morning TDM in selected subjects receiving ATV in the evening. Results must be interpreted with caution given the retrospective design of the study.
Lingua originaleEnglish
pagine (da-a)326-333
Numero di pagine8
RivistaHIV Medicine
Stato di pubblicazionePubblicato - 2010


  • HIV-1 infection
  • atazanavir
  • virological outcome


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