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)< 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.

• Authors: M Fabbiani, S Di Giambenedetto, E Ragazzoni, M Colafigli, M Prosperi, R Cauda, P Navarra, A De Luca
• Journal: HIV medicine (HIV Med) Vol. 11 Issue 5 Pg. 326-33 (May 2010) ISSN: 1468-1293 [Electronic] England
• PMID: 20070407 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HIV Protease Inhibitors
• Oligopeptides
• Pyridines
• Atazanavir Sulfate
• Ritonavir
• Bilirubin

Topics

• Adult
• Atazanavir Sulfate
• Bilirubin (blood)
• Drug Administration Schedule
• Drug Interactions
• Drug Monitoring (methods)
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• HIV Infections (blood, drug therapy, virology)
• HIV Protease Inhibitors (administration & dosage, pharmacokinetics)
• HIV-1 (drug effects)
• Humans
• Hyperbilirubinemia (chemically induced)
• Male
• Middle Aged
• Multivariate Analysis
• Oligopeptides (administration & dosage, pharmacokinetics)
• Pyridines (administration & dosage, pharmacokinetics)
• Retrospective Studies
• Ritonavir (administration & dosage, therapeutic use)
• Treatment Outcome
• Viral Load (drug effects)