High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment.
J Antimicrob Chemother
; 74(1): 135-138, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30239753
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Infecções por HIV
/
Fármacos Anti-HIV
/
Soro
/
Benzoxazinas
/
Citocromo P-450 CYP2B6
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Africa
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Uganda