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

Abstract

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 ≤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. © 2010 British HIV Association.