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J Antimicrob Chemother. 2019 Jan 1;74(1):135-138. doi: 10.1093/jac/dky379.

High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment.

Author information

1
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
2
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
3
Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, Torino, Italy.
4
Department of Public Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.

Abstract

Objectives:

To report the efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults on concomitant anti-TB treatment and analyse factors associated with elevated concentrations in this specific population.

Methods:

Serum efavirenz concentrations in TB/HIV-coinfected Ugandan adults on efavirenz-based ART (600 mg daily) were measured onsite at 2, 8, 12 and 24 weeks of concomitant anti-TB treatment, including rifampicin. Genetic analysis was done retrospectively through real-time PCR by allelic discrimination (CYP2B6 516G>T, rs3745274). Univariable and multivariable logistic regression analyses were done to assess factors potentially associated with elevated efavirenz serum concentrations.

Results:

A total of 166 patients were included in the analysis. The median age was 34 (IQR = 30-40) years, 99 (59.6%) were male, the median CD4 cell count was 195 (IQR = 71-334) cells/mm3 and the median BMI was 19 (IQR = 17.6-21.5)  kg/m2. Almost half of all patients (82, 49.4%) had at least one efavirenz serum concentration above the reference range of 4 mg/L. The serum efavirenz concentrations of patients with genotype CYP2B6 516 TT were consistently above 4 mg/L and significantly higher than those of patients with GG/GT genotypes: CYP2B6 516 TT 9.6 mg/L (IQR = 7.3-13.3) versus CYP2B6 516 GT 3.4 mg/L (IQR = 2.1-5.1) and CYP2B6 516 GG 2.6 mg/L (IQR = 1.3-4.0) (Wilcoxon rank-sum test: P < 0.0001).

Conclusions:

A large proportion of our study participants had at least one efavirenz serum concentration >4 mg/L. The CYP2B6 516 TT genotype was the strongest predictor of high concentration. Physicians should be vigilant that efavirenz serum concentrations may be elevated in patients on concomitant anti-TB treatment and that individualized care is warranted whenever possible.

PMID:
30239753
DOI:
10.1093/jac/dky379

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