Abstract | BACKGROUND: METHODS: Trough EFV concentrations (Cmin) were measured in 54 South African black patients. During TB treatment, EFV dose was 600 mg in patients <50 kg or 800 mg if ≥50 kg. Off TB treatment it was 600 mg. Polymorphisms in CYP2B6, CYP2A6 and UGT2B7 enzymes were sequenced. A multivariate generalized estimating equations model was fitted to assess predictors of high median EFV Cmin. RESULTS: During TB treatment, median EFV Cmin was 3.2 (IQR 2.6-6.3) µg/ml and 3.3 (2.4-9.5) µg/ml in the 800 mg and 600 mg groups, respectively. After TB treatment EFV Cmin was 2.0 (1.4-3.5) µg/ml. Minor allele frequencies for CYP2B6 516G→T, 785A→G, 983T→C, UGT2B7-372G→A, CYP2A6*9B and CYP2A6*17 were 0.31, 0.33, 0.23, 0.29, 0.10 and 0.02, respectively. Haplotypes CYP2B6*6 and CYP2B6*18 were found in 38.9% and 25.9% of patients, respectively. Polymorphisms in all three CYP2B6 genes studied (516T-785G-983C) were present in 11.1% of patients and in this group median EFV Cmin was 19.2 (IQR 9.5-20) µg/ml during and 4.7 (IQR 3.5-5.6) µg/ml after TB treatment. The presence of TB treatment and composite genotypes CYP2B6 516 GT/TT, CYP2B6 983 TC/CC and CYP2A6*9B carrier status predicted median EFV Cmin>4 µg/ml. Adverse events due to high EFV concentrations were rare. CONCLUSIONS: Because polymorphisms of EFV metabolizing enzymes are frequent and are associated with elevated EFV concentrations in this population, EFV dose increases are unnecessary when concomitant rifampicin-containing TB treatment is prescribed.
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Authors | Tanuja N Gengiah, Julia H Botha, Nonhlanhla Yende-Zuma, Kogieleum Naidoo, Salim S Abdool Karim |
Journal | Antiviral therapy
(Antivir Ther)
Vol. 20
Issue 3
Pg. 297-306
( 2015)
ISSN: 2040-2058 [Electronic] England |
PMID | 25318122
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Alkynes
- Antitubercular Agents
- Benzoxazines
- Cyclopropanes
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Enzyme System
- Cytochrome P-450 CYP2B6
- efavirenz
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Topics |
- Adult
- Alkynes
- Alleles
- Antitubercular Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Benzoxazines
(administration & dosage, adverse effects, pharmacokinetics)
- Coinfection
- Cyclopropanes
- Cytochrome P-450 CYP2B6
(genetics)
- Cytochrome P-450 Enzyme Inhibitors
(administration & dosage, adverse effects, pharmacokinetics)
- Cytochrome P-450 Enzyme System
(genetics)
- Female
- Gene Frequency
- Genotype
- HIV Infections
(drug therapy, virology)
- Haplotypes
- Humans
- Male
- Middle Aged
- Pharmacogenetics
- Polymorphism, Single Nucleotide
- Treatment Outcome
- Tuberculosis
(drug therapy, genetics)
- Young Adult
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