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

Abstract

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.

Keywords :

• CYP2B6
• efavirenz
• Ethiopia
• HIV/AIDS
• rifampicin
• sub-Saharan Africa
• treatment guideline
• tuberculosis

Acknowledgements

The authors thank the study participants for their willingness to participate and the research staff for their participation in data collection, patient recruitment and follow-up. The authors are grateful to Lilleba Bohman for her dedicated technical assistance.

Disclaimer

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Financial & competing interests disclosure

This study was supported by grants from European & Developing Countries Clinical Trials Partnership (EDCTP grant number: CT.2005.32030.001) and SIDA (grant numbers HIV-2006-031, SWE 2007-270), Swedish research council (grant number VR 521-2011-3437). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This study was supported by grants from European & Developing Countries Clinical Trials Partnership (EDCTP grant number: CT.2005.32030.001) and SIDA (grant numbers HIV-2006-031, SWE 2007-270), Swedish research council (grant number VR 521-2011-3437). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.