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

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dc.contributor.authorBraun, Amrei von
dc.contributor.authorCastelnuovo, Barbara
dc.contributor.authorLedergerber, Bruno
dc.contributor.authorCusato, Jessica
dc.contributor.authorBuzibye, Allan
dc.contributor.authorKambugu, Andrew
dc.contributor.authorFehr, Jan
dc.contributor.authorCalcagno, Andrea
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorSekaggya-Wiltshire, Christine
dc.date.accessioned2023-03-03T17:30:23Z
dc.date.available2023-03-03T17:30:23Z
dc.date.issued2019
dc.description.abstractTo report the efavirenz serumconcentrations 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 (600mg 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-sumtest: 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.en_US
dc.identifier.citationvon Braun, A., Castelnuovo, B., Ledergerber, B., Cusato, J., Buzibye, A., Kambugu, A., ... & Sekaggya-Wiltshire, C. (2019). High efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatment. Journal of Antimicrobial Chemotherapy, 74(1), 135-138. doi:10.1093/jac/dky379en_US
dc.identifier.other10.1093/jac/dky379
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8066
dc.language.isoenen_US
dc.publisherJournal of Antimicrobial Chemotherapyen_US
dc.subjectHigh efavirenz serum concentrationsen_US
dc.subjectTB/HIV-coinfecteden_US
dc.subjectCYP2B6 516 TT genotypeen_US
dc.subjectAnti-TB treatmenten_US
dc.titleHigh efavirenz serum concentrations in TB/HIV-coinfected Ugandan adults with a CYP2B6 516 TT genotype on anti-TB treatmenten_US
dc.typeArticleen_US
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