Therapeutic monitoring and variability of Atazanavir in HIV-infected patients, with and without HCV coinfection, receiving boosted or unboosted regimens

Mario Regazzi, Paola Villani, Roberto Gulminetti, Maria Cusato, Michela Brandolini, Carmine Tinelli, Alessandra Barassi, Renato Maserati, Laura Sighinolfi, Antonella D'Arminio Monforte, Gian Vico Melzi D'Eril

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Adequate plasma trough concentrations (C trough) of protease inhibitors are required to maintain antiviral activity throughout the dosing interval. Therapeutic drug monitoring is used in clinical practice to optimize dosage and avoid toxic or subtherapeutic drug exposure. The pharmacokinetic variability of Atazanavir (ATV) can be relatively large, as a result of several factors. One of the affecting factors may be hepatic impairment due to hepatitis C virus (HCV) coinfection. Methods: We collected trough plasma samples from human immunodeficiency virus (HIV)-1-infected outpatients, with and without HCV coinfection and/or cirrhosis, receiving stable highly active antiretroviral therapy containing ATV. In the total population, we mainly compared the 2 regimens, 300ATV + 100RTV OD [ritonavir (RTV), once daily (OD)] versus 400ATV OD. We used a threshold value of 0.15 mg/mL, based on the proposed therapeutic range (0.15-0.85 mg/mL). Plasma concentrations of ATV were determined by a validated assay using high-performance liquid chromatography with ultraviolet detection. A total of 214 HIV-infected outpatients were included. For each regimen, we compared 3 groups of subjects HIV+/HCV2, HIV+/HCV+, and HIV+/HCV+ with cirrhosis. Results: In the whole study population, we observed a large variability and found suboptimal C trough levels (<0.15 μg/mL) in 23 subjects (2 belonging to the 300/100 OD group and 21 to the 400 OD group). For the standard dosage regimen of 300ATV + 100RTV OD, we did not find a statistical difference between HIV-infected patients without HCV coinfection versus HIV-infected patients with HCV coinfection median 0.85 (interquartile range 0.53-1.34) and 0.95 (0.70-1.36) mg/mL, respectively. In HIV+/HCV+-infected patients with cirrhosis, we found a median C troughof 0.70 (0.43-1.0) μg/mL, with no statistical difference when compared with HIV+/HCV2 infected patients. For the 400ATVOD (n = 90) dosage regimen, the total median ATV C trough was 0.40 (0.23-1.0) μg/mL. In this group, we found a statistically significant difference between HIV+/HCV2 and HIV+/HCV+-infected patients median C trough was 0.23 (0.11-0.42) and 0.52 (0.20-1.0) mg/mL, respectively. In HIV+/HCV+ subjects with cirrhosis, the C trough median value was 0.42 (0.13-0.75) μg/mL, and there was a significant difference when compared with HIV patients without coinfection. Conclusions: Therapeutic drug monitoring of ATV in patients receiving unboosted regimen may be useful to identify those HIVinfected subjects, with or without HCV coinfection, who may benefit from adding low RTV doses, or the subset of patients in whom removal of RTV could be attempted without the risk of suboptimal plasma ATV exposure.

Original languageEnglish
Pages (from-to)303-308
Number of pages6
JournalTherapeutic Drug Monitoring
Volume33
Issue number3
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Atazanavir
  • HCV coinfection
  • HIV
  • Therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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