Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 202, Issue 5, Pages 717-722Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/655470
Keywords
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Categories
Funding
- Bristol-Myers Squibb
- Boehringer Ingelheim
- Merck
- Gilead Sciences
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Institutes of Health [AI68636, AI38858, AI68634, AI38855]
- virology laboratory with Vanderbilt University [201VC001, 200VC001]
- University of Alabama at Birmingham [200VC011]
- Robert Bosch Foundation Stuttgart
- Hector Foundation
- NIAID [AI069439, AI069472, AI069532, AI069484, AI069432, AI069450, AI069495, AI069434, AI069424, AI69467, AI069423, AI069513, AI069477, AI069465, AI069419, AI069502, AI069474, AI069501, AI069418, AI069494, AI069471, AI069511, AI069452, AI069428]
- NIAID' [AI38858, AI069556, AI069415, AI32782, AI046376-05S4, AI46370, AI34853, AI27661, AI25859, AI069470]
- [RR000095]
- [BRS-ACURE-06-00140-T001]
- [AI51966]
- [RR024996]
- [AI062435]
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In AIDS Clinical Trials Group protocols 384, A5095, and A5097s, we characterized relationships between 22 polymorphisms in CYP2B6, ABCB1, and CYP3A5; plasma efavirenz exposure; and/or treatment responses. A stepwise logistic regression procedure selected polymorphisms associated with reduced drug clearance adjusted for body mass index and the composite CYP2B6 516/983 genotype. Relationships between selected polymorphisms and treatment responses were characterized by competing risk methodology. Association analyses involved 821 individuals (317 for pharmacokinetics and 643 for treatment response). Models that included CYP2B6 516/983 genotype best predicted pharmacokinetics. Slow-metabolizer genotypes were associated with increased central nervous system events among white participants and decreased virologic failure among black participants.
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