ABSTRACT
Human immunodeficiency virus 1 (HIV-1) protease inhibitors are important components
of highly active antiretroviral therapy and have had a profound impact on the natural
history of HIV and AIDS. However, in the era of highly active antiretroviral therapy
(HAART), drug-induced hepatotoxicity or liver injury has emerged as an important potential
complication of combination antiretroviral therapy, particularly those regimens containing
protease inhibitors (PIs). Liver injury has been associated each of the six PIs currently
approved by the U. S. Food and Drug Administration (FDA), most commonly with administration
of full dose ritonavir (600 mg bid or 400 mg bid with saquinavir). However, this regimen
has been largely replaced by the use of low-dose ritonavir (≤ 200 mg bid) to pharmacologically
"boost" other PI, such as lopinavir or indinavir, which has not been associated with
an increased risk of hepatotoxicity compared with other PIs. Coinfection with hepatitis
C virus (HCV) and B virus (HBV) remains an important risk factor for the development
of HAART-associated liver injury. Although studies indicate that coinfected patients
can be safely treated with PIs, such patients should be closely monitored. In addition,
although unsubstantiated, some experts recommend evaluation or treatment, or both,
of underlying chronic viral hepatitis prior to the initiation of antiretroviral therapy.
Further research is needed to understand the etiopathogenesis of PI-associated liver
injury, particularly among patients with hepatitis B or C infection.
KEYWORDS
HIV - protease inhibitors - hepatotoxicity - HBV - HCV
