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Paradoxically elevated efavirenz concentrations in HIV/tuberculosis-coinfected patients with CYP2B6 516TT genotype on rifampin-containing antituberculous therapy

Kwara, Awewuraa,b; Lartey, Margaretc; Sagoe, Kwamena Wc; Court, Michael Hd

doi: 10.1097/QAD.0b013e3283427e05
Research Letters

Some individuals have higher efavirenz plasma concentrations during rifampin-containing tuberculosis (TB) therapy, contrary to the expected induction effect of rifampin. Among HIV-infected patients without (n = 38) and with TB on rifampin-containing therapy (n = 18), we tested the hypothesis that drug–gene interaction may explain the highly variable drug interactions. Two-way analysis of variance revealed a significant interaction between CYP2B6 516G→T polymorphism and rifampin-containing therapy, suggesting that efavirenz dose adjustment may need to be individualized on the basis of the patient's genotype.

aThe Miriam Hospital

bWarren Alpert Medical School of Brown University, Providence, Rhode Island

cUniversity of Ghana Medical School, Accra, Ghana

dDepartment of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts, USA.

Received 30 September, 2010

Accepted 8 November, 2010

Correspondence to Awewura Kwara, MD, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906, USA. Tel: +1 401 793 2463; fax: +1 401 793 4704; e-mail: akwara@lifespan.org

© 2011 Lippincott Williams & Wilkins, Inc.