Pharmacogenomics and Pharmacokinetics of Efavirenz 400 or 600 mg in 184 Treatment-Naive HIV-Infected Patients in China

Abstract

Background: The pharmacogenomics and pharmacokinetics/pharmacodynamics of 400 mg efavirenz have rarely been reported. Materials & methods: A total of 184 treatment-naive HIV-infected patients were randomly assigned (1:1) to receive a lower dose (tenofovir disoproxil 200 mg, efavirenz 400 mg and lamivudine) or a standard dose regimen. Relationships between pharmacogenomics and efavirenz pharmacokinetics/pharmacodynamics were explored at 48 weeks. Results: There was no relationship between pharmacogenomics and adverse reactions of the central nervous system and antiretoviral efficacy. CYP2B6 516G>T, 785A>G, 18492C>T and ABCB1 3435C>T T/C were associated with higher efavirenz plasma levels in the standard but not the lower dose group. No relationship was found between pharmacogenomics and antiretoviral efficacy. Patients who were <60 kg had higher efavirenz concentration compared with those with weight ≥60 kg when using 600 mg efavirenz, this was not observed with 400 mg efavirenz. Conclusion: The effect of pharmacogenomics and body weight on the efavirenz concentration was significant in the 600 mg group but not in the 400 mg group.

Keywords::

• efavirenz
• lower dose
• pharmacogenomics
• pharmacokinetics/pharmacodynamics

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/pgs-2019-0169

Author contributions

R Chen performed this research and wrote the manuscript. J Chen designed this research and revised the manuscript. JN Xun helped with the experiment. ZL Hu and Q Huang collected the blood samples from Nanjing and Kunming. RF Zhang, YZ Shen and L Liu collected the blood sample from Shanghai. C Steinhart revised the manuscript. HZ Lu was PI and the corresponding author.

Acknowledgments

The authors thank Niubing for his coordination of statistical analysis.

Financial & competing interests disclosure

This study was funded by the Shanghai Shenkang Hospital Development Center (no. 16CR1018A), the National Natural Science Foundation of China (no. 81600480) and the 13th Five-year National Major Science and Technology Project (nos. 2017ZX09304027 and 2017ZX10202101004). 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 by the Shanghai Public Health Clinical Center or have followed the principles outlined in the Declaration of Helsinki for all human experimental investigations. In addition, investigations involving human subjects, informed consent has been obtained from the participants involved.

Data sharing statement

Data are available indefinitely from the first author.

Additional information

Funding

his study was funded by the Shanghai Shenkang Hospital Development Center (no. 16CR1018A), the National Natural Science Foundation of China (no. 81600480) and the 13th Five-year National Major Science and Technology Project (nos. 2017ZX09304027 and 2017ZX10202101004). 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.