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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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Hauptverfasser: Ngaimisi, Eliford (VerfasserIn) , Habtewold, Abiy (VerfasserIn) , Minzi, Omary (VerfasserIn) , Makonnen, Eyasu (VerfasserIn) , Mugusi, Sabina (VerfasserIn) , Amogne, Wondwossen (VerfasserIn) , Yimer, Getnet (VerfasserIn) , Riedel, Klaus-Dieter (VerfasserIn) , Janabi, Mohammed (VerfasserIn) , Aderaye, Getachew (VerfasserIn) , Mugusi, Ferdinand (VerfasserIn) , Bertilsson, Leif (VerfasserIn) , Aklillu, Eleni (VerfasserIn) , Burhenne, Jürgen (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: July 5, 2013
In: PLOS ONE
Year: 2013, Jahrgang: 8, Heft: 7, Pages: 1-13
ISSN:1932-6203
DOI:10.1371/journal.pone.0067946
Online-Zugang: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
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 22.11.2021
Beschreibung:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0067946

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