Assessing the impact of hepatitis C virus coinfection on lopinavir/ritonavir trough concentrations in HIV-infected patients
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- Calza, L., Mosca, L., Pocaterra, D. et al. Eur J Clin Pharmacol (2011) 67: 143. doi:10.1007/s00228-010-0904-4
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Chronic hepatitis C is an emerging issue in the management of human immunodeficiency virus (HIV) disease because both diseases have the same route of transmission, leading to a very high prevalence of hepatitis C virus (HCV)-coinfection in the HIV-positive patient population. Lopinavir is extensively metabolized by the hepatic cytochrome P450 3A4, and the pharmacokinetics of this protease inhibitor (PI) could be influenced by liver impairment. However, data currently available on the impact of HCV-coinfection on lopinavir plasma concentrations are both limited and conflicting.
This was an observational, open-label study in which adult HIV-infected outpatients on stable antiretroviral treatment that included two nucleoside reverse transcriptase inhibitors (NRTIs) plus lopinavir/ritonavir for at least 4 weeks were asked to participate. The trough plasma concentration (Ctrough) of lopinavir and ritonavir was assessed at steady state by a validated high-performance liquid chromatography–tandem mass spectrometry method.
A total of 65 HIV-positive patients were enrolled in the study. These patients were stratified into two groups based on the absence/presence of HCV-coinfection: 45 were monoinfected (HIV+/HCV−) and 20 were coinfected (HIV+/HCV+). The lopinavir Ctrough in plasma was comparable between HIV+/HCV+ and HIV+/HCV− patients, without any statistically significant difference (geometric mean ratio 0.89, 95% confidence interval 0.61–1.42; p = 0.581). The mean ritonavir Ctrough was also comparable in the two groups. Almost all samples were found to be within the therapeutic plasma level range (97% in HIV+/HCV− group and 100% in HIV+/HCV+ group). No correlation was found between lopinavir plasma levels and adverse events (such as diarrhoea and hypertriglyceridaemia) or immune-virological parameters of HIV disease.
Among the HIV-positive patients participating in this study, the pharmacokinetics of lopinavir/ritonavir did not significantly change in those HIV-positive patients coinfected with HCV and in the absence of liver cirrhosis.