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

Volumn 8, Issue 7, 2013, Pages

  Ngaimisi, Eliford ^a,b   Habtewold, Abiy ^a,c   Minzi, Omary ^b   Makonnen, Eyasu ^c   Mugusi, Sabina ^a,e   Amogne, Wondwossen ^c,f   Yimer, Getnet ^c   Riedel, Klaus Dieter ^d   Janabi, Mohammed ^b   Aderaye, Getachew ^c   Mugusi, Ferdinand ^b   Bertilsson, Leif ^a   Aklillu, Eleni ^a   Burhenne, Juergen ^d  

^a KAROLINSKA INSTITUTE   (Sweden)

^b MUHIMBILI UNIVERSITY OF HEALTH AND ALLIED SCIENCES   (Tanzania)

^c ADDIS ABABA UNIVERSITY   (Ethiopia)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e MUHIMBILI NATIONAL HOSPITAL   (Tanzania)

^f KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

8 HYDROXYEFAVIRENZ; CYTOCHROME P450 2B6; CYTOCHROME P450 3A5; DRUG METABOLITE; EFAVIRENZ; GLUCURONOSYLTRANSFERASE 2B7; LAMIVUDINE; MULTIDRUG RESISTANCE PROTEIN 1; ORGANIC ANION TRANSPORTER 2; STAVUDINE; TENOFOVIR; UNCLASSIFIED DRUG; ZIDOVUDINE;

ADULT; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; COHORT ANALYSIS; DRUG BLOOD LEVEL; ETHIOPIA; ETHNIC DIFFERENCE; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION; GENOTYPE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PHARMACOGENETICS; PROSPECTIVE STUDY; TANZANIA;

ADULT; AFRICA SOUTH OF THE SAHARA; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; ARYL HYDROCARBON HYDROXYLASES; BENZOXAZINES; CD4 LYMPHOCYTE COUNT; CYTOCHROME P-450 CYP3A; ETHNIC GROUPS; FEMALE; GENOTYPE; GLUCURONOSYLTRANSFERASE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; ORGANIC ANION TRANSPORTERS; P-GLYCOPROTEIN; PHARMACOGENETICS; PROSPECTIVE STUDIES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84879813185     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0067946     Document Type: Article

References (38)

1. Prugnolle F, Manica A, Balloux F, (2005) Geography predicts neutral genetic diversity of human populations. Curr Biol 15: R159-160.
2. Cavalli-Sforza LL MP, Piazza A (1994) The History and Geography of Human Genes. New Jersy: Princeton University press. 535 p.
3. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, et al. (2003) The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306: 287-300.
4. Belanger AS, Caron P, Harvey M, Zimmerman PA, Mehlotra RK, et al. (2009) Glucuronidation of the antiretroviral drug efavirenz by UGT2B7 and an in vitro investigation of drug-drug interaction with zidovudine. Drug Metab Dispos 37: 1793-1796.
5. Cho DY, Ogburn ET, Jones D, Desta Z, (2011) Contribution of N-glucuronidation to efavirenz elimination in vivo in the basal and rifampin-induced metabolism of efavirenz. Antimicrob Agents Chemother 55: 1504-1509.
6. Ngaimisi E, Mugusi S, Minzi OM, Sasi P, Riedel KD, et al. (2010) Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients. Clin Pharmacol Ther 88: 676-684.
7. Habtewold A, Amogne W, Makonnen E, Yimer G, Riedel KD, et al. (2011) Long-term effect of efavirenz autoinduction on plasma/peripheral blood mononuclear cell drug exposure and CD4 count is influenced by UGT2B7 and CYP2B6 genotypes among HIV patients. The Journal of antimicrobial chemotherapy 66: 2350-2361.
8. Mukonzo JK, Roshammar D, Waako P, Andersson M, Fukasawa T, et al. (2009) A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans. Br J Clin Pharmacol 68: 690-699.
9. Swart M, Ren Y, Smith P, Dandara C, (2012) ABCB1 4036A>G and 1236C>T Polymorphisms Affect Plasma Efavirenz Levels in South African HIV/AIDS Patients. Front Genet 3: 236.
10. Mukonzo JK, Okwera A, Nakasujja N, Luzze H, Sebuwufu D, et al. (2013) Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study. BMC Infect Dis 13: 261.
11. Elens L, Vandercam B, Yombi JC, Lison D, Wallemacq P, et al. (2010) Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. Pharmacogenomics 11: 1223-1234.
12. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, et al. (2004) Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos 32: 348-358.
13. Faucette SR, Zhang TC, Moore R, Sueyoshi T, Omiecinski CJ, et al. (2007) Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J Pharmacol Exp Ther 320: 72-80.
14. Habtewold A, Amogne W, Makonnen E, Yimer G, Nylen H, et al. (2012) Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients. Pharmacogenomics J.
15. Stohr W, Back D, Dunn D, Sabin C, Winston A, et al. (2008) Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir Ther 13: 675-685.
16. Burger D, van der Heiden I, la Porte C, van der Ende M, Groeneveld P, et al. (2006) Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism. Br J Clin Pharmacol 61: 148-154.
17. Hodder S, Arasteh K, De Wet J, Gathe J, Gold J, et al. (2012) Effect of gender and race on the week 48 findings in treatment-naive, HIV-1-infected patients enrolled in the randomized, phase III trials ECHO and THRIVE. HIV Med 13: 406-415.
18. Schackman BR, Ribaudo HJ, Krambrink A, Hughes V, Kuritzkes DR, et al. (2007) Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy: results of ACTG A5095. J Acquir Immune Defic Syndr 46: 547-554.
19. Yimer G, Amogne W, Habtewold A, Makonnen E, Ueda N, et al. (2012) High plasma efavirenz level and CYP2B6*6 are associated with efavirenz-based HAART-induced liver injury in the treatment of naive HIV patients from Ethiopia: a prospective cohort study. Pharmacogenomics J 12: 499-506.
20. Yimer G, Ueda N, Habtewold A, Amogne W, Suda A, et al. (2011) Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients. PLoS One 6: e27810.
21. Mugusi S, Ngaimisi E, Janabi M, Minzi O, Bakari M, et al. (2012) Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania. PLoS One 7: e40180.
22. Gounden V, van Niekerk C, Snyman T, George JA, (2010) Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients. AIDS Res Ther 7: 32.
23. Aklillu E, Mugusi S, Ngaimisi E, Hoffmann MM, Konig S, et al. (2011) Frequency of the SLCO1B1 388A>G and the 521T>C polymorphism in Tanzania genotyped by a new LightCycler(R)-based method. Eur J Clin Pharmacol 67: 1139-1145.
24. Lopez-Cortes LF, Ruiz-Valderas R, Marin-Niebla A, Pascual-Carrasco R, Rodriguez-Diez M, et al. (2005) Therapeutic drug monitoring of efavirenz: trough levels cannot be estimated on the basis of earlier plasma determinations. J Acquir Immune Defic Syndr 39: 551-556.
25. Burhenne J, Matthee AK, Pasakova I, Roder C, Heinrich T, et al. (2010) No evidence for induction of ABC transporters in peripheral blood mononuclear cells in humans after 14 days of efavirenz treatment. Antimicrob Agents Chemother 54: 4185-4191.
26. Mugusi SF, Ngaimisi E, Janabi MY, Mugusi FM, Minzi OM, et al. (2012) Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania. Antivir Ther 17: 265-274.
27. Aklillu E, Dandara C, Bertilsson L, Masimirembwa C (2007) Pharmacogenetics of Cytochrome P450s in African Populations: Clinical and Molecular Evolutionary Implications. In: Suarez-Kurtz G, ed. Pharmacogenomics in Admixed Populations. Austin, TX: Landes Bioscience, 99-119.
28. Jamshidi Y, Moreton M, McKeown DA, Andrews S, Nithiyananthan T, et al. (2010) Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: implications for efavirenz dosing in HIV infection. J Antimicrob Chemother 65: 2614-2619.
29. di Iulio J, Fayet A, Arab-Alameddine M, Rotger M, Lubomirov R, et al. (2009) In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function. Pharmacogenet Genomics 19: 300-309.
30. Maimbo M, Kiyotani K, Mushiroda T, Masimirembwa C, Nakamura Y, (2012) CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans. Eur J Clin Pharmacol 68: 267-271.
31. Heil SG, van der Ende ME, Schenk PW, van der Heiden I, Lindemans J, et al. (2012) Associations between ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles in relation to efavirenz and nevirapine pharmacokinetics in HIV-infected individuals. Ther Drug Monit 34: 153-159.
32. Gebeyehu E, Engidawork E, Bijnsdorp A, Aminy A, Diczfalusy U, et al. (2011) Sex and CYP3A5 genotype influence total CYP3A activity: high CYP3A activity and a unique distribution of CYP3A5 variant alleles in Ethiopians. Pharmacogenomics J 11: 130-137.
33. Nyakutira C, Roshammar D, Chigutsa E, Chonzi P, Ashton M, et al. (2008) High prevalence of the CYP2B6 516G->T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. Eur J Clin Pharmacol 64: 357-365.
34. Hardwick RJ, Amogne W, Mugusi S, Yimer G, Ngaimisi E, et al. (2012) beta-defensin Genomic Copy Number Is Associated With HIV Load and Immune Reconstitution in Sub-Saharan Africans. J Infect Dis.
35. Lugada ES, Mermin J, Kaharuza F, Ulvestad E, Were W, et al. (2004) Population-based hematologic and immunologic reference values for a healthy Ugandan population. Clin Diagn Lab Immunol 11: 29-34.
36. Tsegaye A, Messele T, Tilahun T, Hailu E, Sahlu T, et al. (1999) Immunohematological reference ranges for adult Ethiopians. Clin Diagn Lab Immunol 6: 410-414.
37. Kassu A, Tsegaye A, Petros B, Wolday D, Hailu E, et al. (2001) Distribution of lymphocyte subsets in healthy human immunodeficiency virus-negative adult Ethiopians from two geographic locales. Clin Diagn Lab Immunol 8: 1171-1176.
38. Saathoff E, Schneider P, Kleinfeldt V, Geis S, Haule D, et al. (2008) Laboratory reference values for healthy adults from southern Tanzania. Trop Med Int Health 13: 612-625.