final program.qxd - Parallels Plesk Panel

OP 9.4
Antiretroviral agents in HIV-infected patients with cirrhosis
Salmon-Ceron D, Sogni P, Taburet AM.
Universite Paris V, Faculte Cochin, Service de Maladies Infectieuses, Hospital Cochin, 27
rue du Faubourg Saint Jacques, 75014 Paris. dominique.salmon@cch.aphp-paris.fr
Coinfection with HIV and hepatitis B or C viruses results in accelerated liver damage as
compared with persons with chronic viral hepatitis alone.
The use of HAART has led to significant improvement of hepatic related mortality and
survival. However effective HAART use may also contribute to liver disease impairement
by the hepatic toxicity of these drugs.
The long term impact of some reverse transcriptase inhibitors (NRTI), although non metabolised
by the liver, may be particularly severe on hepatic mitochondria leading to
steatosis.
Other classes such as HIV-1 protease inhibitors (PI) and non nucleoside reverse
transcriptase inhibitors (NNRTI) are metabolized by the hepatic CYP enzymes and may
accumulate in case of cirrhosis. This raises the possibility of significant interactions
between antiretroviral medications and hepatic impairment induced by chronic viral
hepatitis. Although the data are limited, the pharmacokinetics of several antiretroviral
medications have been shown to be significantly altered in the presence of liver disease.
Moreover, the relation between high antiretroviral concentrations and toxicity has been
clearly demonstrated with certain PI and NNRTI. Further more, most PI have been
associated with hepatic abnormalities, hyperlipemia and decrease insulin sensitivity,
which themselves have been linked with hepatic steatosis.
Although it is possible to initiate an antiretroviral at the standard dose in patients with
cirrhosis (the therapeutic margin with antiretrovirals is wide), dose adjustment and
therapeutic drug monitoring are useful particularly with PI and NNRTI, to adjust the dose
and avoid adverse events. It is also recommended that the most hepatotoxic drugs be
avoided, notably didanosine, didanosine+stavudine, nevirapine, and full-dose ritonavir.
ABSTRACTS
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