Hepatotoxicity and nelfinavir: a meta-analysis.
OBJECTIVE
The inclusion of protease inhibitors in 3-drug highly active antiretroviral regimens for treating patients who are infected with human immunodeficiency virus-1 has had a significant impact in increasing survival and decreasing morbidity. However, the effectiveness of this class of drugs may be compromised by the occurrence of drug-related hepatotoxicity, which is problematic especially in individuals co-infected with hepatitis viruses. Based on its clinical and pharmacologic profile, especially its unique pattern of resistance, nelfinavir has been used frequently as a first-line protease-inhibitor therapy for human immunodeficiency virus-1-infected patients. The aim of this study was to identify the relative potential for developing hepatotoxicity for nelfinavir vs other protease inhibitors.


METHODS
An exploratory meta-analysis of liver enzyme level increases was conducted in a combined total of 4268 patients derived from 3 large recently conducted prospective and retrospective clinical trials and a prospective cohort study.


RESULTS
The results indicate that among 4 commercially available protease inhibitors and a 2-protease inhibitor combination, nelfinavir and indinavir are associated with the lowest rates of occurrence of severe hepatotoxicity (ie, combined estimates of liver enzyme level increases of 2.9% and 3.1%, respectively). The low rate of occurrence of severe hepatotoxicity for nelfinavir was shown even among patients co-infected with hepatitis viruses.


CONCLUSIONS
In conclusion, these data provide support for the conclusion that differences in the potential for hepatotoxicity do exist among the commercially available protease inhibitors.
Bruno
Raffaele
R
Division of Infectious and Tropical Diseases, Istituto di Ricovero e Cura a Carattere Scientifico San Mateo Hospital--University of Pavia, Italy.
Sacchi
Paolo
P
Maiocchi
Laura
L
Zocchetti
Cristina
C
Filice
Gaetano
G
D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D006801:Humans; D019469:Indinavir / Q000009:adverse effects; D008099:Liver / Q000201:enzymology; D019888:Nelfinavir / Q000009:adverse effects*
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir