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Sir,

Some degree of hepatotoxicity was associated with the use of protease inhibitors (PIs) soon after their introduction into the antiretroviral market.1 Although under the term hepatotoxicity a variety of heterogeneous conditions of liver damage may be included, here the definition is broadly applied to any form of alteration of liver function tests (LFTs).

The clinical use of lopinavir/ritonavir, as a component of antiretroviral regimens, was found to be associated with an incidence of hepatotoxicity ranging from 1% to 9.5% in clinical trials.1 In this setting, an additional factor contributing to the likelihood of developing hepatotoxicity while on highly active antiretroviral therapy (HAART) is represented by the concomitant presence of HCV infection, which was found to be associated with a 4.7-fold increase in LFT abnormalities in lopinavir/ritonavir intakes compared with HCV-free subjects.2 However, generalization from clinical trial data has limited informative value, since no studies specifically addressed to evaluate lopinavir/ritonavir hepatotoxicity have been carried out in geographical areas with high prevalence rates of HIV/HCV co-infection. Among the possible mechanisms accounting for lopinavir/ritonavir hepatotoxicity in HIV/HCV co-infected patients, a role for higher drug concentrations resulting from reduced cytochrome P450 activity has been suggested. In patients with HIV/HCV co-infection, various degrees of liver function impairment were found to be proportionally associated with higher pharmacokinetic parameters of amprenavir, nelfinavir, indinavir, ritonavir and nevirapine.1,3 In HIV-infected patients with mild to moderate HCV-related liver cirrhosis, Arribas et al.4 found lopinavir and ritonavir area-under-the-curve (AUC) increases of 20% and 148–280%, respectively. However, few data are available on the pharmacokinetics of lopinavir/ritonavir in non-cirrhotic HIV/HCV co-infected patients. In an observational, comparative, prospective study at the Department of Infectious Diseases of the University of Torino, in a high prevalence area for HIV/HCV co-infection, 149 treatment-naive HIV-infected patients were consecutively administered an antiretroviral regimen consisting of lopinavir/ritonavir and two nucleoside-nucleotide reverse transcriptase inhibitors.

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