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

To describe raltegravir pharmacokinetics at steady-state in HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV) treatment with (n5) and without (n5) advanced liver cirrhosis (ChildPugh C). This was a non-randomized, Phase I, parallel-assignment, open-label pharmacokinetic study in HIV/HCV-coinfected patients with ChildPugh 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 AUC(012) and C-12 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 (ChildPugh C). Despite the higher exposure, raltegravir was safe and well tolerated.