title: A pilot study on the efficacy, pharmacokinetics and safety of atazanavir in patients with end-stage liver disease.
abstract: Antiretroviral combinations including atazanavir are currently not recommended in HIV-infected patients with end-stage liver disease (ESLD). The objective of our study was to evaluate efficacy, pharmacokinetics and safety of unboosted atazanavir in HIV-infected patients with ESLD screened for orthotopic liver transplantation (OLT(x)). Patients and methods Single-arm, 24 week pilot study. Atazanavir-naive patients undergoing highly active antiretroviral therapy were switched to atazanavir 400 mg/day plus two non-thymidine nucleoside reverse transcriptase inhibitors. Results Fifteen patients (10 males and 5 females) were included. In the study period, 2 patients were transplanted and 10 completed 24 weeks of atazanavir treatment. Median area under the concentration-time curve at week 4 was 19 211 ng.h/mL (IQR = 8959-27 500). At week 24, median atazanavir trough concentrations (C(trough)) per patient calculated across the study were above the minimum effective concentration (MEC = 100 ng/mL) in 8 of 10 subjects. Atazanavir C(trough) time-point values were always above the MEC in five patients. The other three subjects experienced only one determination below the MEC, with median atazanavir C(trough) levels across the study being above the MEC in two of them. At 8 of 11 time-points when atazanavir and proton pump inhibitors (PPIs) were co-administered and at 16 of 19 time-points in which patients had a concomitant tenofovir association, atazanavir C(trough) was above the MEC. Conclusions Unboosted atazanavir showed a favourable pharmacokinetic profile and was able to maintain or gain immuno-virological eligibility for OLT(x) in all patients. Limited biochemical toxicities (including unconjugated hyperbilirubinaemia) and allowance of concomitant administration of tenofovir and PPIs were observed.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.forename: Stefania
authors.initials: S
authors.lastname: Cocchi
authors.forename: Alice
authors.initials: A
authors.lastname: Motta
authors.forename: Sara
authors.initials: S
authors.lastname: Ciaffi
authors.forename: Mauro
authors.initials: M
authors.lastname: Codeluppi
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Di Benedetto
authors.forename: Michele
authors.initials: M
authors.lastname: Masetti
authors.forename: Marco
authors.initials: M
authors.lastname: Floridia
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Diego
authors.initials: D
authors.lastname: Pinetti
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.forename: Alfio
authors.initials: A
authors.lastname: Bertolini
authors.forename: Roberto
authors.initials: R
authors.lastname: Esposito
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D000069446:Atazanavir Sulfate; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008107:Liver Diseases; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010865:Pilot Projects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044967:Serum / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate