TY - JOUR
T1 - Hepatotoxicity associated with antiretroviral therapy containing HIV-1 protease inhibitors
AU - Sulkowski, Mark S.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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 anti-retroviral therapy. Further research is needed to understand the etiopathogenesis of PI-associated liver injury, particularly among patients with hepatitis B or C infection.
AB - 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 anti-retroviral therapy. Further research is needed to understand the etiopathogenesis of PI-associated liver injury, particularly among patients with hepatitis B or C infection.
KW - HBV
KW - HCV
KW - HIV
KW - Hepatotoxicity
KW - Protease inhibitors
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U2 - 10.1055/s-2003-39949
DO - 10.1055/s-2003-39949
M3 - Article
C2 - 12800071
AN - SCOPUS:0038621557
VL - 23
SP - 183
EP - 193
JO - Seminars in Liver Disease
JF - Seminars in Liver Disease
SN - 0272-8087
IS - 2
ER -