title: Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders.
abstract: Complex drug-drug interactions have been reported with concurrent administration of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors (PIs), leading to relevant limitations of the therapeutic options for patients coinfected with hepatitis C virus (HCV) and HIV. However, little is known about the pharmacokinetics and drug interactions between TVR and antiretrovirals in HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1-coinfected patients with advanced liver fibrosis treated with TVR-based triple anti-HCV therapy. No significant differences were observed in the pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15 of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir declined below their minimum effective concentrations even in association with TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR exposure was seen in patients concomitantly given amprenavir versus those given atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion, this study highlighted the feasibility of maintaining the current antiretroviral regimen in HIV/HCV-coinfected patients, even when significant interactions with TVR are predictable, whenever a change of HIV PIs is not deemed appropriate.
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy. Electronic address: laura.milazzo@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Milazzo
authors.affiliation: Unit of Clinical Pharmacology, Luigi Sacco University Hospital, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Calvi
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasoni
authors.affiliation: Department of Biomedical and Clinical Sciences, Section of Biostatistics, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzali
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ronzi
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Peri
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Ridolfo
authors.affiliation: Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: Department of Biomedical and Clinical Sciences L. Sacco, III Division of Infectious Diseases, University of Milan, Via GB Grassi 74, 20157 Milan, Italy.
authors.forename: Spinello
authors.initials: S
authors.lastname: Antinori
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies
chemical_list: D044966:Anti-Retroviral Agents; D000998:Antiviral Agents; D009842:Oligopeptides; C486464:telaprevir
keywords: Antiretroviral therapy; Drug interactions; Pharmacokinetics; Telaprevir