[Antiretroviral agents in HIV-infected patients with cirrhosis].
Since highly active antiretroviral therapies became available, the future of HIV-infected patients has been transformed. However, 20 to 25% of HIV patients are co-infected with hepatitis B or C viruses, and the course of these diseases has worsened, since these patients have an enhanced sensitivity to the hepatic toxicity of antiretrovirals. The relation between high antiretroviral concentrations and toxicity has been clearly demonstrated with certain protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTI) that have a predominantly hepatic metabolism (CYP4503A4). The nucleoside reverse transcriptase inhibitors (NRTI) are not predominantly metabolized by the liver, but may nevertheless be toxic for the liver through mitochondrial involvement. The hepatic toxicity observed in a patient treated with early or delayed antiretrovirals may be due to a cytolytic, cholestatic or mixed, direct or indirect, mechanism. Before initiating antiretroviral treatments, hepatic fibrosis must be explored (punch biopsy, biological fibrosis test, and Child-Pugh's score). It is recommended that the most hepatotoxic drugs be avoided, notably didanosine, didanosine+stavudine, nevirapine, and full-dose ritonavir. Although it is possible to initiate an antiretroviral at the standard dose in patients with cirrhosis (the therapeutic margin with antiretrovirals is wide), early assays are essential, particularly with PI and NNRTI, to adjust the dose and avoid adverse events. In any event rigorous monitoring is a must.
Salmon-Céron
Dominique
D
Université Paris V, Faculté Cochin, Service de Maladies Infectieuses, Hôspital Cochin, 27 rue du Faubourg Saint Jacques, 75014 Paris. dominique.salmon@cch.aphp-paris.fr
Sogni
Philippe
P
Spiridon
Gabriela
G
Taburet
Anne-Marie
AM
D044966:Anti-Retroviral Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D011480:Protease Inhibitors