Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C)

• Published in: Journal of antimicrobial chemotherapy Vol. 69; no. 2; pp. 471 - 475
• Main Authors: Hernández-Novoa, Beatriz, Moreno, Ana, Pérez-Elías, María J, Quereda, Carmen, Dronda, Fernando, Casado, José L, Madrid-Elena, Nadia, Aguilar, Mónica, Fumero, Emilio, Moltó, José, Moreno, Santiago
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.02.2014
• Subjects: Adult; Antiretroviral drugs; Female; Hepatitis; Hepatitis C - blood; Hepatitis C - drug therapy; Hepatitis C - epidemiology; Hepatitis C virus; HIV; HIV Infections - blood; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Integrase Inhibitors - blood; HIV Integrase Inhibitors - pharmacokinetics; HIV Integrase Inhibitors - therapeutic use; Human immunodeficiency virus; Humans; Liver cirrhosis; Liver Cirrhosis - blood; Liver Cirrhosis - drug therapy; Liver Cirrhosis - epidemiology; Male; Middle Aged; Protease inhibitors; Pyrrolidinones - blood; Pyrrolidinones - pharmacokinetics; Pyrrolidinones - therapeutic use; Raltegravir Potassium; plasma concentration; integrase inhibitors; end-stage liver disease
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkt386

To describe raltegravir pharmacokinetics at steady-state in HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV) treatment with (n = 5) and without (n = 5) advanced liver cirrhosis (Child-Pugh C). This was a non-randomized, Phase I, parallel-assignment, open-label pharmacokinetic study in HIV/HCV-coinfected patients with Child-Pugh grade C hepatic cirrhosis. We recruited clinically stable HIV/HCV-coinfected adult patients with controlled HIV viraemia (<50 copies/mL) for at least 6 months. Raltegravir (400 mg twice daily) was added under fasting conditions for 5 days to the successful ritonavir-boosted protease inhibitor-based ARV regimen. The trial was registered in the ClinicalTrials.gov database (NCT01289951) (LIVERAL). Raltegravir AUC0-12 and C12 were increased 1.72-fold (90% CI, 1.02 to 2.92) and 6.58-fold (90% CI, 2.92 to14.85), respectively, in patients with advanced liver cirrhosis. No safety issues were identified and raltegravir was well tolerated by all patients. Raltegravir plasma levels are increased in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). Despite the higher exposure, raltegravir was safe and well tolerated.