Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations
Objectives: We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. Methods: ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enro...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
July 5, 2013
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| In: |
PLOS ONE
Year: 2013, Volume: 8, Issue: 7, Pages: 1-13 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0067946 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0067946 Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067946 
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| Author Notes: | Eliford Ngaimisi, Abiy Habtewold, Omary Minzi, Eyasu Makonnen, Sabina Mugusi, Wondwossen Amogne, Getnet Yimer, Klaus-Dieter Riedel, Mohammed Janabi, Getachew Aderaye, Ferdinand Mugusi, Leif Bertilsson, Eleni Aklillu, Juergen Burhenne |
MARC
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| 245 | 1 | 0 | |a Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes |b a parallel-group prospective cohort study in two sub-Saharan Africa populations |c Eliford Ngaimisi, Abiy Habtewold, Omary Minzi, Eyasu Makonnen, Sabina Mugusi, Wondwossen Amogne, Getnet Yimer, Klaus-Dieter Riedel, Mohammed Janabi, Getachew Aderaye, Ferdinand Mugusi, Leif Bertilsson, Eleni Aklillu, Juergen Burhenne |
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| 520 | |a Objectives: We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. Methods: ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Result: Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. Conclusion: We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations. | ||
| 650 | 4 | |a Africa | |
| 650 | 4 | |a African people | |
| 650 | 4 | |a Alleles | |
| 650 | 4 | |a Antiretroviral therapy | |
| 650 | 4 | |a Highly-active antiretroviral therapy | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Population genetics | |
| 700 | 1 | |a Habtewold, Abiy |e VerfasserIn |4 aut | |
| 700 | 1 | |a Minzi, Omary |e VerfasserIn |4 aut | |
| 700 | 1 | |a Makonnen, Eyasu |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mugusi, Sabina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Amogne, Wondwossen |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yimer, Getnet |e VerfasserIn |4 aut | |
| 700 | 1 | |a Riedel, Klaus-Dieter |e VerfasserIn |0 (DE-588)1034229605 |0 (DE-627)745128432 |0 (DE-576)381859460 |4 aut | |
| 700 | 1 | |a Janabi, Mohammed |e VerfasserIn |4 aut | |
| 700 | 1 | |a Aderaye, Getachew |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mugusi, Ferdinand |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Aklillu, Eleni |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burhenne, Jürgen |d 1963- |e VerfasserIn |0 (DE-588)1034228889 |0 (DE-627)745126987 |0 (DE-576)381858197 |4 aut | |
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