title: Effects of hepatitis C virus infection on the pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected patients.
abstract: Most antiretrovirals are metabolized in the liver, and overexposure could be more common in human immunodeficiency virus (HIV)-infected patients with hepatic impairment. Careful monitoring of potential drug-related liver injury in clinical practice is necessary. The aim of our study was to analyze the trough concentrations (C (trough)) of atazanavir (ATV) in the plasma of HIV/hepatitis C virus (HCV)-co-infected patients and to compare the values with those of a HIV-infected control population. C (trough) values (22-26 h after last intake) of atazanavir, following the administration of atazanavir/ritonavir 300/100 mg once daily as part of antiretroviral therapy, were assessed by HPLC. We also collected data on dosing of atazanavir, and on demographic (age, gender, and ethnicity), physiological (weight and body mass index), and clinical parameters (CD4+ cell count, HIV-RNA viremia, co-medication, and hepatitis C co-infection). A total of 28 Caucasian HIV-infected adults were studied, of whom 13 were HIV/HCV co-infected. No baseline characteristics differed between the two cohorts, except statistically significant differences regarding ALT, AST, and total bilirubin. The median (range) plasma ATV C (trough) levels were 0.62 (0.05-3.22) μg/ml in HIV patients and 0.32 (0.04-3.37) μg/ml in HIV/HCV patients. Thus, there was no significant difference in plasma trough levels of atazanavir in the two cohorts. In our patients with mild impairment of hepatic function caused by HCV infection, atazanavir C (trough) was comparable in HIV-infected and HIV/HCV-co-infected patients.
authors.affiliation: Department of Infectious Diseases, San Martino Hospital Genoa, University of Genoa, Largo Rosanna Benzi, 10, 16132, Genoa, Italy. antonio.dibiagio@hsanmartino.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rosso
authors.forename: Arianna
authors.initials: A
authors.lastname: Loregian
authors.forename: Silvana
authors.initials: S
authors.lastname: Pagni
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cenderello
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D060085:Coinfection / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006526:Hepatitis C / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019438:Ritonavir