Drug Transporter and Metabolizing Enzyme Gene Variants and Nonnucleoside Reverse-Transcriptase Inhibitor Hepatotoxicity

This nested case-control study examined relationships between MDR1, CYP2B6, and CYP3A4 variants and hepatotoxicity during antiretroviral therapy with either efavirenz- or nevirapine-containing regimens. Decreased risk of hepatotoxicity was associated with MDR1 3435C→;T (odds ratio, 0.254; P = .021)....

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Veröffentlicht in:	Clinical infectious diseases 2006-09, Vol.43 (6), p.779-782
Hauptverfasser:	Ritchie, Marylyn D., Haas, David W., Motsinger, Alison A., Donahue, John P., Erdem, Huso, Raffanti, Stephen, Rebeiro, Peter, George, Alfred L., Kim, Richard B., Haines, Jonathan L., Sterling, Timothy R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Adult Anti-HIV Agents - adverse effects Anti-HIV Agents - metabolism Anti-HIV Agents - therapeutic use Antiretroviral drugs Antiretrovirals Aryl Hydrocarbon Hydroxylases - genetics Benzoxazines Biological and medical sciences Biological variation Case-Control Studies Chemical and Drug Induced Liver Injury Cytochrome P-450 CYP2B6 Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System - genetics Dimensionality reduction Drug therapy Drug toxicity and drugs side effects treatment Exanthema Female Fever Genes Genes, MDR Genetic Variation Genotype Hepatitis Hepatitis antigens Hepatotoxicity HIV Infections - drug therapy HIV-1 HIV/AIDS Human genetics Humans Infectious diseases Liver - drug effects Liver Diseases - genetics Liver Diseases - virology Male Medical genetics Medical sciences Nevirapine - adverse effects Nevirapine - metabolism Nevirapine - therapeutic use Oxazines - adverse effects Oxazines - metabolism Oxazines - therapeutic use Oxidoreductases, N-Demethylating - genetics Pharmacology. Drug treatments Reverse transcriptase inhibitors Reverse Transcriptase Inhibitors - adverse effects Reverse Transcriptase Inhibitors - metabolism Reverse Transcriptase Inhibitors - therapeutic use Toxicity Toxicity: digestive system
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Zusammenfassung:	This nested case-control study examined relationships between MDR1, CYP2B6, and CYP3A4 variants and hepatotoxicity during antiretroviral therapy with either efavirenz- or nevirapine-containing regimens. Decreased risk of hepatotoxicity was associated with MDR1 3435C→;T (odds ratio, 0.254; P = .021). An interaction between MDR1 and hepatitis B surface antigen status predicted risk with 82% accuracy (P < .001).
ISSN:	1058-4838 1537-6591
DOI:	10.1086/507101