Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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
PLoS ONE, Volume 8, No. 7, Article e67946, Year 2013
Notification
URL copied to clipboard!
Description
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. © 2013 Ngaimisi et al.
Authors & Co-Authors
Ngaimisi, Eliford
Sweden, Stockholm
Karolinska Institutet
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Habtewold, Abiy
Sweden, Stockholm
Karolinska Institutet
Ethiopia, Addis Ababa
School of Medicine
Minzi, Omary Mashiku Sylivester
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Makonnen, Eyasu
Ethiopia, Addis Ababa
School of Medicine
Mugusi, Sabina Ferdinand
Sweden, Stockholm
Karolinska Institutet
Tanzania, Dar es Salaam
Muhimbili National Hospital
Amogne, Wondwossen
Sweden, Stockholm
Karolinska Universitetssjukhuset
Ethiopia, Addis Ababa
School of Medicine
Yimer, Getnet
Ethiopia, Addis Ababa
School of Medicine
Riedel, Klaus Dieter
Germany, Heidelberg
Universität Heidelberg
Janabi, Mohamed Y.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Aderaye, Getachew
Ethiopia, Addis Ababa
School of Medicine
Mugusi, Ferdinand M.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Bertilsson, Leif N.
Sweden, Stockholm
Karolinska Institutet
Aklillu, Eleni
Sweden, Stockholm
Karolinska Institutet
Burhenne, Jürgen
Germany, Heidelberg
Universität Heidelberg
Statistics
Citations: 120
Authors: 14
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0067946
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative
Study Locations
Ethiopia
Tanzania