Metabolic and kidney disorders correlate with high atazanavir concentrations in HIV-infected patients: Is it time to revise atazanavir dosages?

Cristina Gervasoni, Paola Meraviglia, Davide Minisci, Laurenzia Ferraris, Agostino Riva, Simona Landonio, Valeria Cozzi, Nitin Charbe, Lara Molinari, Giuliano Rizzardini, Emilio Clementi, Massimo Galli, Dario Cattaneo

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Ritonavir-boosted atazanavir (ATV/r) is a relatively well tolerated antiretroviral drug. However, side effects including hyperbilirubinemia, dyslipidemia, nephrolithiasis and cholelithiasis have been reported in the medium and long term. Unboosted ATV may be selected for some patients because it has fewer gastrointestinal adverse effects, less hyperbilirubinemia and less impact on lipid profiles. Methods: We investigated the distribution of ATV plasma trough concentrations according to drug dosage and the potential relationship between ATV plasma trough concentrations and drug-related adverse events in a consecutive series of 240 HIV-infected patients treated with ATV/r 300/100 mg (68%) or ATV 400 mg (32%). Results: 43.9% of patients treated with ATV/r 300/100 mg had ATV concentrations exceeding the upper therapeutic threshold. A significant and direct association has been observed between the severity of hyperbilirubinemia and ATV plasma trough concentrations (ATV concentrations: 271 [77-555], 548 [206-902], 793 [440-1164], 768 [494-1527] and 1491 [1122-1798] ng/mL in patients with grade 0, 1, 2, 3 and 4 hyperbilirubinemia, respectively). In an exploratory analysis we found that patients with dyslipidemia or nephrolitiasis had ATV concentrations significantly higher (582 [266-1148], and 1098 [631-1238] ng/mL, respectively) (p

Original languageEnglish
Article numbere0123670
JournalPLoS One
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 15 2015

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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