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PLoS One. 2014 Feb 14;9(2):e88497. doi: 10.1371/journal.pone.0088497. eCollection 2014.

Therapeutic drug monitoring and pharmacogenetic study of HIV-infected ethnic Chinese receiving efavirenz-containing antiretroviral therapy with or without rifampicin-based anti-tuberculous therapy.

Author information

1
Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
2
Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan ; Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
3
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
4
Department of Pharmacy, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
5
Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
6
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
7
Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan.
8
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
9
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan ; China Medical University, Taichung, Taiwan.

Abstract

OBJECTIVES:

Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese.

METHODS:

HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively.

RESULTS:

From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33-0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97-9.59) in multivariate analysis.

CONCLUSIONS:

Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.

PMID:
24551111
PMCID:
PMC3925114
DOI:
10.1371/journal.pone.0088497
[Indexed for MEDLINE]
Free PMC Article

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