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Is there a need to increase the dose of efavirenz during concomitant rifampicin-based antituberculosis therapy in sub-Saharan Africa?: the HIV-TB pharmagene study

Aims: The current HIV treatment guidelines are inconsistent about the need for weight-based efavirenz dose adjustment during rifampicin containing antituberculosis (anti-TB) cotreatment. We investigated effect of rifampicin-based anti-TB cotreatment on plasma efavirenz exposure and treatment outcome...

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Main Authors: Habtewold, Abiy (Author) , Makonnen, Eyasu (Author) , Amogne, Wondwossen (Author) , Yimer, Getnet (Author) , Aderaye, Getachew (Author) , Bertilsson, Leif (Author) , Burhenne, Jürgen (Author) , Aklillu, Eleni (Author)
Format: Article (Journal)
Language:English
Published: 1 Apr 2015
In: Pharmacogenomics
Year: 2015, Volume: 16, Issue: 10, Pages: 1047-1064
ISSN:1744-8042
DOI:10.2217/pgs.15.35
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.2217/pgs.15.35
Verlag, lizenzpflichtig, Volltext: https://www.futuremedicine.com/doi/10.2217/pgs.15.35
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Author Notes:Abiy Habtewold, Eyasu Makonnen, Wondwossen Amogne, Getnet Yimer, Getachew Aderaye, Leif Bertilsson, Jürgen Burhenne & Eleni Aklillu
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Summary:Aims: The current HIV treatment guidelines are inconsistent about the need for weight-based efavirenz dose adjustment during rifampicin containing antituberculosis (anti-TB) cotreatment. We investigated effect of rifampicin-based anti-TB cotreatment on plasma efavirenz exposure and treatment outcome, considering effect of CYP2B6 genotype and bodyweight. Patients & methods: HIV-only (arm 1, n = 285) or TB-HIV (arm 2, n = 208) coinfected patients were enrolled and received efavirenz-based ART alone or with rifampicin-based anti-TB therapy, respectively. Plasma efavirenz concentrations at 4th and 16th weeks, viral load and CD4 cell count at 24th and 48th weeks were determined. Results: The mean plasma efavirenz concentration at weeks 4 (p = 0.03) and 16 (p = 0.08) was inconsistently higher in arm 2 than arm 1, mainly in CYP2B6*6 carriers. Effect of bodyweight on efavirenz pharmacokinetics was significant only in arm 1, but not in arm 2. Proportion of patients with nondetectable viral load (≤50 copies/ml) at week 24 was higher in arm 1 than arm 2 patients (91.0 vs 76.3%; p = 0.002), but no significant difference was observed at week 48 (89.5 vs 87.8%; p = 0.22). Conclusion: Rifampicin-based anti-TB cotreatment has no significant influence on long-term efavirenz plasma exposure and efficacy. Hence, there is no need to increase the dose of efavirenz during concomitant rifampicin-based anti-TB cotreatment in the sub-Saharan African population.
Item Description:Gesehen am 22.02.2021
Physical Description:Online Resource
ISSN:1744-8042
DOI:10.2217/pgs.15.35

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