Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: An AIDS clinical trials group study

Heather J. Ribaudo, Huan Liu, Matthias Schwab, Elke Schaeffeler, Michel Eichelbaum, Alison A. Motsinger-Reif, Marylyn D. Ritchie, Ulrich M. Zanger, Edward P. Acosta, Gene D. Morse, Roy M. Gulick, Gregory K. Robbins, David Clifford, David W. Haas

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)717-722
Number of pages6
JournalJournal of Infectious Diseases
Volume202
Issue number5
DOIs
StatePublished - Sep 1 2010

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efavirenz
Cytochrome P-450 CYP3A
Acquired Immunodeficiency Syndrome
Pharmacokinetics
Genotype
Clinical Trials
Clinical Protocols
Body Mass Index
Therapeutics
Central Nervous System
Logistic Models
Pharmaceutical Preparations
Cytochrome P-450 CYP2B6

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Ribaudo, H. J., Liu, H., Schwab, M., Schaeffeler, E., Eichelbaum, M., Motsinger-Reif, A. A., ... Haas, D. W. (2010). Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: An AIDS clinical trials group study. Journal of Infectious Diseases, 202(5), 717-722. https://doi.org/10.1086/655470
Ribaudo, Heather J. ; Liu, Huan ; Schwab, Matthias ; Schaeffeler, Elke ; Eichelbaum, Michel ; Motsinger-Reif, Alison A. ; Ritchie, Marylyn D. ; Zanger, Ulrich M. ; Acosta, Edward P. ; Morse, Gene D. ; Gulick, Roy M. ; Robbins, Gregory K. ; Clifford, David ; Haas, David W. / Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response : An AIDS clinical trials group study. In: Journal of Infectious Diseases. 2010 ; Vol. 202, No. 5. pp. 717-722.
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abstract = "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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Ribaudo, HJ, Liu, H, Schwab, M, Schaeffeler, E, Eichelbaum, M, Motsinger-Reif, AA, Ritchie, MD, Zanger, UM, Acosta, EP, Morse, GD, Gulick, RM, Robbins, GK, Clifford, D & Haas, DW 2010, 'Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: An AIDS clinical trials group study', Journal of Infectious Diseases, vol. 202, no. 5, pp. 717-722. https://doi.org/10.1086/655470

Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response : An AIDS clinical trials group study. / Ribaudo, Heather J.; Liu, Huan; Schwab, Matthias; Schaeffeler, Elke; Eichelbaum, Michel; Motsinger-Reif, Alison A.; Ritchie, Marylyn D.; Zanger, Ulrich M.; Acosta, Edward P.; Morse, Gene D.; Gulick, Roy M.; Robbins, Gregory K.; Clifford, David; Haas, David W.

In: Journal of Infectious Diseases, Vol. 202, No. 5, 01.09.2010, p. 717-722.

Research output: Contribution to journalArticle

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T2 - An AIDS clinical trials group study

AU - Ribaudo, Heather J.

AU - Liu, Huan

AU - Schwab, Matthias

AU - Schaeffeler, Elke

AU - Eichelbaum, Michel

AU - Motsinger-Reif, Alison A.

AU - Ritchie, Marylyn D.

AU - Zanger, Ulrich M.

AU - Acosta, Edward P.

AU - Morse, Gene D.

AU - Gulick, Roy M.

AU - Robbins, Gregory K.

AU - Clifford, David

AU - Haas, David W.

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AB - 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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