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 AUC0-4 h of darunavir was 36% lower in the presence of TVR (AUC0-4 h 15 007 ng h/mL and 9563 ng h/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4 h, 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 (AUC0-4 h, 9840 ng h/mL and 13 345 ng h/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.

Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders / L. Milazzo, D. Cattaneo, E. Calvi, C. Gervasoni, C. Mazzali, P. Ronzi, A.M. Peri, A.L. Ridolfo, A. D'Avolio, S. Antinori. - In: INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS. - ISSN 0924-8579. - 45:5(2015), pp. 545-549. [10.1016/j.ijantimicag.2014.12.035]

Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders

C. Mazzali;P. Ronzi;S. Antinori
Supervision
2015

Abstract

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 AUC0-4 h of darunavir was 36% lower in the presence of TVR (AUC0-4 h 15 007 ng h/mL and 9563 ng h/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4 h, 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 (AUC0-4 h, 9840 ng h/mL and 13 345 ng h/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.
Antiretroviral therapy; Drug interactions; Pharmacokinetics; Telaprevir; Adult; Aged; Anti-Retroviral Agents; Antiviral Agents; Female; HIV Infections; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Oligopeptides; Plasma; Prospective Studies; Drug Interactions
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/661285
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