Genetic variants of drug metabolizing enzymes and drug transporter (ABCB1) as possible biomarkers for adverse drug reactions in an HIV/AIDS cohort in Zimbabwe

Current HIV Research

Volumn 11, Issue 6, 2013, Pages 481-490

  Dhoro, Milcah ^a,b   Ngara, Bernard ^a   Kadzirange, Gerald ^b   Nhachi, Charles ^b   Masimirembwa, Collen ^a  

^a African Institute of Biomedical Science and Technology   (Zimbabwe)

^b UNIVERSITY OF ZIMBABWE   (Zimbabwe)

Author keywords

Adverse drug reactions; Antiretroviral treatment; Genetic polymorphisms; HIV AIDS

Indexed keywords

BILE SALT EXPORT PUMP; CYTOCHROME P450 2A6; CYTOCHROME P450 2B6; CYTOCHROME P450 3A5; DRUG METABOLIZING ENZYME; EFAVIRENZ; ISONIAZID; LAMIVUDINE; MULTIDRUG RESISTANCE PROTEIN 1; NEVIRAPINE; STAVUDINE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ADULT; AGE; ALLELE; ARTICLE; CASE CONTROL STUDY; CENTRAL NERVOUS SYSTEM DISEASE; CONTROLLED STUDY; ENZYME ACTIVITY; FEMALE; GENDER; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIPODYSTROPHY; MAJOR CLINICAL STUDY; MALE; PERIPHERAL NEUROPATHY; PHARMACOGENETICS; POLYMERASE CHAIN REACTION; PROSPECTIVE STUDY; SKIN ALLERGY;

ADULT; ANTI-RETROVIRAL AGENTS; ANTITUBERCULAR AGENTS; ARYL HYDROCARBON HYDROXYLASES; ARYLAMINE N-ACETYLTRANSFERASE; CASE-CONTROL STUDIES; DRUG HYPERSENSITIVITY; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION STUDIES; GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; P-GLYCOPROTEIN; POLYMORPHISM, GENETIC; PROSPECTIVE STUDIES; REGRESSION ANALYSIS; RISK FACTORS; ZIMBABWE;

EID: 84894042969     PISSN: 1570162X     EISSN: 18734251     Source Type: Journal    
DOI: 10.2174/1570162x113119990048     Document Type: Article

References (92)

1. Alastair JJ, Wood MD: Pharmacogenomics - Drug Disposition, Drug Targets, and Side Effects. New Engl J Med 2003; 348: 538-549.
2. William E, Howard L. Pharmacogenomics - Drug Disposition, Drug Targets, and Side Effects. New Engl J Med 2003; 2: 3-7.
3. Ingelman-Sundberg M. Pharmacogenomic Biomarkers for Prediction of Severe Adverse Drug Reactions. New Engl J Med 2008; 358(6): 637-639.
4. Ma MK, Woo MH, McLeod HL. Genetic basis of drug metabolism. Am J Health Syst Pharm 2002; 59: 2061-2019.
5. Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 2007; 116(3): 496-526.
6. Mitchell RS, Bell JC. Clinical implications of isoniazid, PAS and streptomycin blood levels in pulmonary tuberculosis. Trans Am Clin Climatol Assoc 1957-1958; 69: 98-102.
7. Evans DA, Manley KA, McKusick VA. Genetic control of isoniazid metabolism in man. Br Med J 1960; 2: 485-491.
8. Likanonsakul S, Rattanatham T, Feangvad S, et al. HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai patients. AIDS Res Ther 2009; 6: 22.
9. Martin AM, Nolan D, James I, et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 2005; 19: 97-99.
10. Nyakutira C, Roshammar D, Chigutsa E, et al. 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 2008; 64: 357-365.
11. Haas DW, Ribaudo HJ, Kim RB, et al. Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. AIDS 2004; 18: 2391-2400.
12. Tozzi V, Libertone R, Liuzzi G. HIV pharmacogenetics in clinical practice: recent achievements and future challenges. Curr HIV Res 2008; 6: 544-554.
13. Tarr PE, Taffe P, Bleiber G, et al. Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders. J Infect Dis 2005; 191: 1419-1426.
14. Martinjak-Dvorsek I, Gorjup V, Horvat M, Noc M. Acute isoniazid neurotoxicity during preventive therapy. Crit Care Med 2000; 28: 567-8.
15. Watkins RC, Hambrick EL, Benjamin G, Chavda SN. Isoniazid toxicity presenting as seizures and metabolic acidosis. J Natl Med Assoc 1990; 82(1): 57, 62, 64.
16. Izzedine H, Hulot JS, Villard E, et al. Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. J Infect Dis 2006 194: 1481-1491.
17. Rodriguez-Novoa S, Labarga P, Soriano V, et al. Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study. Clin Infect Dis 2009; 48: e108-e116.
18. Hetherington S, Hughes AR, Mosteller M, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002; 359: 1121-1122.
19. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002; 359: 727-732.
20. Martin AM, Nolan D, Gaudieri S, et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci USA 2004; 101: 4180-4185.
21. Pozniak AL, Miller RF, Lipman MC, et al. BHIVA treatment guidelines for tuberculosis (TB)/HIV infection 2005. HIV Med 2005; 6 Suppl 2: 62-83.
22. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, Desta Z. 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 2003; 306: 287-300.
23. Tsuchiya K, Gatanaga H, Tachikawa N, et al. Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem Biophys Res Commun 2004; 319: 1322-1326.
24. Rotger M, Colombo S, Furrer H, et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 2005; 15: 1-5.
25. Rodriguez-Novoa S, Barreiro P, Rendon A, Jimenez-Nacher I, Gonzalez-Lahoz J, Soriano V. Influence of 516G>T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin Infect Dis 2005; 40: 1358-1361.
26. Rotger M. CYP2B6: Explaining Efavirenz Pharmacokinetics. HIV Pharmacogenetics 2007; 2.
27. Rotger M, Tegude H, Colombo S, et al. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 2007; 81: 557-566.
28. Nolan ML, Greenberg AE, Fowler MG. A review of clinical trials to prevent mother-to-child HIV-1 transmission in Africa and inform rational intervention strategies. AIDS 2002; 16; 1991-9.
29. Kiertiburanakul S, Sungkanuparph S, Charoenyingwattana A, Mahasirimongkol S, Sura T, Chantratita W. Risk factors for nevirapine-associated rash among HIV-infected patients with low CD4 cell counts in resource-limited settings. Curr HIV Res 2008; 6: 65-69.
30. Pollard RB, Robinson P, Dransfield K. Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin Ther 1998; 20: 1071-1092.
31. Metry DW, Lahart CJ, Farmer KL, Hebert AA. Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine. J Am Acad Dermatol 2001; 44: 354-357.
32. Ananworanich J, Moor Z, Siangphoe U, et al. Incidence and risk factors for rash in Thai patients randomized to regimens with nevirapine, efavirenz or both drugs. AIDS 2005; 19: 185-192.
33. Antinori A, Baldini F, Girardi E, et al. Female sex and the use of anti-allergic agents increase the risk of developing cutaneous rash associated with nevirapine therapy. AIDS 2001; 15: 1579-1581.
34. Sharma AM, Novalen M, Tanino T, Uetrecht JP. 12-OH-Nevirapine Sulfate, Formed in the Skin, Is Responsible for Nevirapine-Induced Skin Rash. Chem Res Toxicol 2013; 26: 817-827.
35. Riska P, Lamson M, MacGregor T, et al. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Disposit 1999; 27: 895-901.
36. Erickson DA, Mather G, Trager WF, Levy RH, Keirns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Disposit 1999; 27: 1488-1495.
37. Penzak SR, Kabuye G, Mugyenyi P, et al. Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda. HIV Med 2007; 8: 86-91.
38. Kuehl P, Zhang J, Lin Y, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001; 27: 383-391.
39. Gozalo C, Gerard L, Loiseau P, et al. Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naive HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial. Basic Clin Pharmacol Toxicol 2011; 109: 513-520.
40. Martin AM, Nolan D, James I, et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 2005; 19: 97-99.
41. Vitezica ZG, Milpied B, Lonjou C, et al. HLA-DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS 2008; 22: 540-1.
42. Chantarangsu S, Mushiroda T, Mahasirimongkol S, et al. HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in Thai HIV-infected patients. Pharmacogenet Genomics 2009; 19: 139-146.
43. Vitezica ZG, Milpied B, Lonjou C, et al. HLA-DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS 2008; 22: 540-1.
44. Yarchoan R, Pluda JM, Perno CF, et al. Initial clinical experience with dideoxynucleosides as single agents and in combination therapy. Ann N Y Acad Sci 1990; 616: 328-43.
45. Cherry CL, Skolasky RL, Lal L, et al. Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort. Neurology 2006; 66: 867-73.
46. Hiratsuka M, Kishikawa Y, Takekuma Y, et al. Genotyping of the N-acetyltransferase2 polymorphism in the prediction of adverse drug reactions to isoniazid in Japanese patients. Drug Metab Pharmacokinet 2002; 17: 357-62.
47. Dragovic G, Jevtovic D. Nucleoside reverse transcriptase inhibitor usage and the incidence of peripheral neuropathy in HIV/AIDS patients. Antivir Chem Chemother 2003; 14: 281-284.
48. Peltier AC, Russell JW. Advances in understanding drug-induced neuropathies. Drug Saf 2006; 29: 23-30.
49. Bell DA, Taylor JA, Butler MA, et al. Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. Carcinogenesis 1993; 14: 1689-1692.
50. Vatsis KP, Weber WW, Bell DA, et al. Nomenclature for N-acetyltransferases. Pharmacogenetics 1995; 5: 1-17.
51. Zhou SF, Di YM, Chan E, et al. Clinical pharmacogenetics and potential application in personalized medicine. Curr Drug Metab 2008; 9: 738-784.
52. Kinzig-Schippers M, Tomalik-Scharte D, Jetter A, et al. Should We Use N-Acetyltransferase Type 2 Genotyping To Personalize Isoniazid Doses? Antimicrob Agents Chemother 2005; 49(5): 1733-1738.
53. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction, and natural course of HIV-1 proteaseinhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study. Lancet 1999; 353(9170): 2093-2099.
54. Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor- related lipodystrophy syndrome. AIDS 2000; 14: 25-32.
55. Hadigan C, Meigs JB, Corcoran C, et al. Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy. Clin Infect Dis 2001; 32: 130-139.
56. Saint-Marc T, Partisani M, Poizot-Martin I, et al. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long term nucleoside analogue therapy. AIDS 1999; 13: 1659-1667.
57. Maher B, Alfirevic A, Vilar FJ, Wilkins EG, Park BK, Pirmohamed M. TNF-alpha promoter region gene polymorphisms in HIV-positive patients with lipodystrophy. AIDS 2002; 16: 2013-2018.
58. Nolan D, Moore C, Castley A, et al. Tumour necrosis factor-alpha gene -238G/A promoter polymorphism associated with a more rapid onset of lipodystrophy. AIDS 2003; 17: 121-123.
59. Haufroid V. Genetic polymorphisms of ATP-binding cassette transporters ABCB1 and ABCC2 and their impact on drug disposition. Curr Drug Targets 2011; 12: 631-646.
60. Kimchi-Sarfaty C, Oh JM, Kim IW, et al. A silent polymorphism in the MDR1 gene changes substrate specificity. Science 2007; 315: 525-528.
61. Ribaudo HJ, Liu H, Schwab M, et al. Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study. J Infect Dis 2010; 202: 717-722.
62. Fellay J, Marzolini C, Meaden ER, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 2002; 359: 30-36.
63. Haas DW, Smeaton LM, Shafer RW, et al. Pharmacogenetics of long-term responses to antiretroviral regimens containing Efavirenz and/or Nelfinavir: an Adult Aids Clinical Trials Group Study. J Infect Dis 2005; 192: 1931-1942.
64. Nasi MBV, Pinti M, Bellodi C, et al. MDR1 C3435T genetic polymorphism does not influence the response to antiretroviral therapy in drug-naive HIV-positive patients. AIDS 2003; 17: 1696-1698.
65. Winzer R, Langmann P, Zilly M, et al. No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of lopinavir and efavirenz during antiretroviral treatment. Eur J Med Res 2003; 8: 531-534.
66. Hove RF, CE N. 6th Essential Medicines List and Standard Treatment Guidelines for Zimbabwe. (Welfare MoHC ed., 6th edition. Harare: The National Medicine and Therapeutics Policy Advisory Committee 2011.
67. A guide for adaptation and implementation: Antiretroviral therapy for HIV Infection in adults and adolescence. [http://www.who.int/hiv/topics/treatment/guide_for_adaptation.pdf]
68. Nemaura T, Dhoro M, Nhachi C, Kadzirange G, Chonzi P, Masimirembwa C. Evaluation of the Prevalence, Progression and Severity of Common Adverse Reactions (Lipodystrophy, CNS, Peripheral Neuropathy, and Hypersensitivity Reactions) Associated with Anti-Retroviral Therapy (ART) and Anti-Tuberculosis Treatment in Outpatients in Zimbabwe. J AIDS Clin Res 2013; 4: 203.
69. Matimba A, Oluka MN, Ebeshi BU, et al. Establishment of a biobank and pharmacogenetics database of African populations. Eur J Hum Genet 2008; 16: 780-3.
70. Maimbo M, Kiyotani K, Mushiroda T, Masimirembwa C, Y N. CYP2B6 genotype is a strong predictor of systemic exposure 5 to efavirenz in HIV-infected Zimbabweans. Eur J Clin Pharmacol 2012; 68: 267-271.
71. Kwara A, Lartey M, Sagoe KW, Kenu E, Court MH: CYP2B6, CYP2A6 and UGT2B7 genetic polymorphisms are predictors of efavirenz mid-dose concentration in HIV-infected patients. AIDS 2009; 23: 2101-6.
72. Hoffmeyer S, Burk O, von Ritcher O, et al. Functional polymorphisms of the human multidrug resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97: 3473-8.
73. Ameyaw MM, Regateiro F, Li T, et al. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 2001; 11(3): 217-21.
74. Schaeffeler E, Eichelbaum M, Brinkmann U, et al. Frequency of C3435T polymorphism of MDR1 gene in African people 2001; 358(9279): 383-4.
75. Gatanaga H, Yazaki H, Tanuma J, et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS 2007; 21: 264-5.
76. Veloso S, Olona M, García F. Effect of TNF-α genetic variants and CCR5Δ32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards. BMC Med Genet 2010; 11: 63.
77. Ebeshi BU, Bolaji OO, CM M. Arylamine N-acetyltransferase 2 (NAT2) single nucleotide polymorphisms' frequencies in Nigerian populations. Afr J Pharm Pharmacol Res 2011; 1: 001-6.
78. Dandara C, Masimirembwa CM, Magimba A, et al. Arylamine N-acetyltransferase (NAT2) genotypes in Africans: the identification of a new allele with nucleotide changes 481C>T and 590G>A. Pharmacogenetics 2002; 12: 1-4.
79. Stahle L, Moberg L, Svensson JO, Sonnerborg A. Efavirenz plasma concentrations in HIV-infected patients: inter- and intraindividual variability and clinical effects. Ther Drug Monit 2004; 26: 267-70.
80. Chantarangsu S, Cressey TR, Mahasirimongkol S, et al. Influence of CYP2B6 polymorphisms on the persistence of plasma nevirapine concentrations following a single intra-partum dose for the prevention of mother to child transmission in HIV-infected Thai women. J Antimicrob Chemother 2009; 64: 1265-73.
81. Wyen C, Hendra H, Vogel M, et al: Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother 2008; 61: 914-8.
82. Mahungu T, Smith C, Turner F, et al. Cytochrome P450 2B6 516G-->T is associated with plasma concentrations of nevirapine at both 200 mg twice daily and 400 mg once daily in an ethnically diverse population. HIV Med 2009; 10: 310-7.
83. Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS 2001; 15: 71-5.
84. di Iulio J, Fayet A, Arab-Alameddine M, et al. In vivo analysis of efavirenz metabolism in individuals with impaired CYP2A6 function. Pharmacogenet Genomics 2009; 19: 300-9.
85. Gounden V, van Niekerk C, Snyman T, George JA. 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 2010; 7: 32.
86. Fumaz CR, Munoz-Moreno JA, Moltó J. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr 2005; 38(5): 560-5.
87. Nemaura T, Chalres N, Collen M. Impact of gender, weight and CYP2B6 genotype on efavirenz exposure in patients on HIV/AIDS and TB treatment: Implications for individualising therapy. Afr J Pharm Pharmacol 2012; 6(29): 2188-93.
88. Schipani A, Wyen C, Mahungu T, Hendra H, et al. HIV/AIDS. GCNf: Integration of population pharmacokinetics and pharmacogenetics: an aid to optimal nevirapine dose selection in HIV-infected individuals. J Antimicrob Chemother 2011; 66: 1332-9.
89. Wangsomboonsiri W, Mahasirimongkol S, Chantarangsu S, et al. Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen. Clin Infect Dis 2010; 50: 597-604.
90. Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs 2000; 59(6): 1251-60.
91. Mehlotra RK, Bockarie MJ, Zimmerman PA. CYP2B6 983T>C polymorphism is prevalent in West Africa but absent in Papua New Guinea: implications for HIV/AIDS treatment. Br J Clin Pharmacol 2007; 64: 391-5.
92. Altman RB, Kroemer HK, McCarty CA, Ratain MJ, Roden D. Pharmacogenomics: will the promise be fulfilled? Nat Rev Genet 2011; 12: 69-73.