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- Title
Mid-dosing interval concentration of atazanavir and virological outcome in patients treated for HIV-1 infection.
- Authors
Fabbiani, M.; Di Giambenedetto, S.; Ragazzoni, E.; Colafigli, M.; Prosperi, M.; Cauda, R.; Navarra, P.; De Luca, A.
- Abstract
Objectives We investigated the clinical significance of monitoring the mid-dosing interval atazanavir (ATV) concentration (measured 12 ± 2 h after intake; C12 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 C12 h during routine out-patient visits, and we correlated C12 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 C12 h≤0.23 mg/L showed virological failure in 41.2% of cases, whereas samples with a C12 h>0.23 mg/L showed virological failure in 14.3% of cases ( P=0.021). In multivariate analysis, C12 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 C12 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.
- Subjects
HIV-positive persons; HIV infections; DRUG analysis; CLINICAL drug trials; DRUG monitoring
- Publication
HIV Medicine, 2010, Vol 11, Issue 5, p326
- ISSN
1464-2662
- Publication type
Article
- DOI
10.1111/j.1468-1293.2009.00785.x