CYP2B6 genotype, but not rifampicin-based anti-TB cotreatments, explains variability in long-term efavirenz plasma exposure

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

• 1 Steingart KR, Jotblad S, Robsky K et al. Higher-dose rifampin for the treatment of pulmonary tuberculosis: a systematic review. Int. J. Tuberc. Lung Dis. 15(3), 305–316 (2011).
  Medline CASGoogle Scholar
• 2 WHO. HIV/AIDS programme. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach 2010 revision. http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf
  Google Scholar
• 3 Nachega JB, Rosenkranz B, Simon G, Chaisson RE, Diacon A, Taljaard J. Management of adult active tuberculosis disease in era of HIV pandemic, current practices and future perspectives. Infect. Disord. Drug Targets 11(2), 134–143 (2011).
  Medline CASGoogle Scholar
• 4 Lopez-Cortes LF, Ruiz-Valderas R, Viciana P et al. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin. Pharmacokinet. 41(9), 681–690 (2002).•• Demonstrates that rifampicin coadministration reduces the efavirenz area under the concentration–time curve by 25%.
  Medline CASGoogle Scholar
• 5 Rekic D, Roshammar D, Mukonzo J, Ashton M. In silico prediction of efavirenz and rifampicin drug–drug interaction considering weight and CYP2B6 phenotype. Br. J. Clin. Pharmacol. 71(4), 536–543 (2011).
  Medline CASGoogle Scholar
• 6 Mukonzo JK, Okwera A, Nakasujja N et al. 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 (2013).
  Medline CASGoogle Scholar
• 7 Ngaimisi E, Mugusi S, Minzi O et al. Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis. Clin. Pharmacol. Ther. 90(3), 406–413 (2011).•• Reports for the first time the CYP2B6 genotype-dependent effect of rifampicin on efavirenz plasma exposure.
  Medline CASGoogle Scholar
• 8 Cohen K, Grant A, Dandara C et al. Effect of rifampicin-based antitubercular therapy and the cytochrome P450 2B6 516G>T polymorphism on efavirenz concentrations in adults in South Africa. Antivir. Ther. 14(5), 687–695 (2009).
  Medline CASGoogle Scholar
• 9 Ren Y, Nuttall JJ, Eley BS et al. Effect of rifampicin on efavirenz pharmacokinetics in HIV-infected children with tuberculosis. J. Acquir. Immune Defic. Syndr. 50(5), 439–443 (2009).
  Medline CASGoogle Scholar
• 10 Gengiah TN, Holford NH, Botha JH, Gray AL, Naidoo K, Abdool Karim SS. The influence of tuberculosis treatment on efavirenz clearance in patients co-infected with HIV and tuberculosis. Eur. J. Clin. Pharmacol. 68(5), 689–695 (2012).
  Medline CASGoogle Scholar
• 11 Kwara A, Lartey M, Sagoe KW, Court MH. Paradoxically elevated efavirenz concentrations in HIV/tuberculosis-coinfected patients with CYP2B6 516TT genotype on rifampin-containing antituberculous therapy. AIDS 25(3), 388–390 (2011).• Reports for the first time the increased efavirenz plasma concentration on rifampicin in CYP2B6*6/*6 genotype patients.
  Medline CASGoogle Scholar
• 12 Rosenkranz SL, Lu D, Marzan F et al. Relationship between weight, efavirenz exposure and virologic suppression in HIV-infected patients on rifampin-based TB treatment in the ACTG A5221 STRIDE study. Clin. Infect. Dis. 57(4), 586–593 (2013).
  MedlineGoogle Scholar
• 13 Orrell C, Cohen K, Conradie F et al. Efavirenz and rifampicin in the South African context: is there a need to dose-increase efavirenz with concurrent rifampicin therapy? Antivir. Ther. 16(4), 527–534 (2011).
  Medline CASGoogle Scholar
• 14 Thompson MA, Aberg JA, Hoy JF et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 308(4), 387–402 (2012).
  Medline CASGoogle Scholar
• 15 Pozniak AL, Coyne KM, Miller RF et al. British HIV Association guidelines for the treatment of TB/HIV coinfection 2011. HIV Med. 12(9), 517–524 (2011).
  Medline CASGoogle Scholar
• 16 US FDA. Sustiva labeling update/dosing adjustment with rifampin. www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm294476.htm
  Google Scholar
• 17 Ngaimisi E, Habtewold A, Minzi O et al. 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 8(7), e67946 (2013).
  Medline CASGoogle Scholar
• 18 Habtewold A, Amogne W, Makonnen E et al. 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. J. Antimicrob. Chemother. 66(10), 2350–2361 (2011).• Reports for the first time that efavirenz autoinduction is long term and influenced by the CYP2B6 genotype.
  Medline CASGoogle Scholar
• 19 Ngaimisi E, Mugusi S, Minzi OM et al. Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients. Clin. Pharmacol. Ther. 88(5), 676–684 (2010).
  Medline CASGoogle Scholar
• 20 Mukonzo JK, Roshammar D, Waako P et al. A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans. Br. J. Clin. Pharmacol. 68(5), 690–699 (2009).• Reports for the first time the association of ABCB1 c.4036A>G with higher plasma efavirenz concentrations.
  Medline CASGoogle Scholar
• 21 Mukonzo JK, Owen JS, Ogwal-Okeng J et al. Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes. PLoS ONE 9(1), e86919 (2014).
  MedlineGoogle Scholar
• 22 Habtewold A, Amogne W, Makonnen E et al. Pharmacogenetic and pharmacokinetic aspects of CYP3A induction by efavirenz in HIV patients. Pharmacogenomics J. 13(6), 484–489 (2013).
  Medline CASGoogle Scholar
• 23 Kunutsor S, Evans M, Thoulass J et al. Ascertaining baseline levels of antiretroviral therapy adherence in Uganda: a multimethod approach. J. Acquir. Immune Defic. Syndr. 55(2), 221–224 (2010).
  MedlineGoogle Scholar
• 24 Tang C, Lin JH, Lu AY. Metabolism-based drug–drug interactions: what determines individual variability in cytochrome P450 induction? Drug Metab. Dispos. 33(5), 603–613 (2005).
  Medline CASGoogle Scholar
• 25 Yenny, Nafrialdi, Djoerban Z, Setiabudy R. Pharmacokinetic interaction between efavirenz and rifampicin in healthy volunteers. Int. J. Clin. Pharmacol. Ther. 49(2), 162–168 (2011).•• Reports that 1 week of rifampicin coadministration significantly reduces efavirenz bioavailability in healthy volunteers.
  Medline CASGoogle Scholar
• 26 Mukonzo JK, Nanzigu S, Rekic D et al. HIV/AIDS patients display lower relative bioavailability of efavirenz than healthy subjects. Clin. Pharmacokinet. 50(8), 531–540 (2011).• Reports significant differences in efavirenz plasma exposure between healthy volunteers and HIV/AIDS patients.
  MedlineGoogle Scholar
• 27 Lindfelt T, O'Brien J, Song JC, Patel R, Winslow DL. Efavirenz plasma concentrations and cytochrome 2B6 polymorphisms. Ann. Pharmacother. 44(10), 1572–1578 (2010).
  Medline CASGoogle Scholar
• 28 Burger D, Van Der Heiden I, La Porte C et al. 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(2), 148–154 (2006).
  Medline CASGoogle Scholar
• 29 Stohr W, Back D, Dunn D et al. Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir. Ther. 13(5), 675–685 (2008).
  Medline CASGoogle Scholar
• 30 Mcilleron H, Schomaker M, Ren Y et al. Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype. AIDS 27(12), 1933–1940 (2013).
  Medline CASGoogle Scholar
• 31 Kwara A, Ramachandran G, Swaminathan S. Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all. Expert Opin. Drug Metab. Toxicol. 6(1), 55–68 (2010).
  Medline CASGoogle Scholar
• 32 Ramachandran G, Hemanth Kumar AK, Rajasekaran S et al. CYP2B6 G516T polymorphism but not rifampin coadministration influences steady-state pharmacokinetics of efavirenz in human immunodeficiency virus-infected patients in south India. Antimicrob. Agents Chemother. 53(3), 863–868 (2009).
  Medline CASGoogle Scholar
• 33 Manosuthi W, Sukasem C, Lueangniyomkul A et al. Impact of pharmacogenetic markers of CYP2B6, clinical factors, and drug–drug interaction on efavirenz concentrations in HIV/tuberculosis-coinfected patients. Antimicrob. Agents Chemother. 57(2), 1019–1024 (2013).
  Medline CASGoogle Scholar
• 34 Friedland G, Khoo S, Jack C, Lalloo U. Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV. J. Antimicrob. Chemother. 58(6), 1299–1302 (2006).
  Medline CASGoogle Scholar
• 35 Ogburn ET, Jones DR, Masters AR, Xu C, Guo Y, Desta Z. Efavirenz primary and secondary metabolism in vitro and in vivo: identification of novel metabolic pathways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylation. Drug Metab. Dispos. 38(7), 1218–1229 (2010).
  Medline CASGoogle Scholar
• 36 Wen X, Wang JS, Neuvonen PJ, Backman JT. Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur. J. Clin. Pharmacol. 57(11), 799–804 (2002).• Demonstrates the inhibitory effect of isoniazid on CYP2A6- and CYP3A4-mediated reactions.
  MedlineGoogle Scholar
• 37 Marques MM, Costa MR, Santana Filho FS et al. Plasmodium vivax chloroquine resistance and anemia in the western Brazilian Amazon. Antimicrob. Agents Chemother. 58(1), 342–347 (2014).
  MedlineGoogle Scholar
• 38 Faucette SR, Zhang TC, Moore R et al. Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J. Pharmacol. Exp. Ther. 320(1), 72–80 (2007).
  Medline CASGoogle Scholar
• 39 Faucette SR, Sueyoshi T, Smith CM, Negishi M, Lecluyse EL, Wang H. Differential regulation of hepatic CYP2B6 and CYP3A4 genes by constitutive androstane receptor but not pregnane X receptor. J. Pharmacol. Exp. Ther. 317(3), 1200–1209 (2006).
  Medline CASGoogle Scholar
• 40 Swart M, Skelton M, Ren Y, Smith P, Takuva S, Dandara C. High predictive value of CYP2B6 SNPs for steady-state plasma efavirenz levels in South African HIV/AIDS patients. Pharmacogenet. Genomics 23(8), 415–427 (2013).
  Medline CASGoogle Scholar
• 41 Swart M, Ren Y, Smith P, Dandara C. ABCB1 4036A>G and 1236C>T polymorphisms affect plasma efavirenz levels in South African HIV/AIDS patients. Front. Genet, 3, 236 (2012).
  Medline CASGoogle Scholar
• 42 Elens L, Vandercam B, Yombi JC, Lison D, Wallemacq P, Haufroid V. Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients. Pharmacogenomics 11(9), 1223–1234 (2010).
  CASGoogle Scholar
• 43 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. 64(4), 357–365 (2008).
  Medline CASGoogle Scholar
• 44 Yimer G, Amogne W, Habtewold A et al. 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(6), 499–506 (2012).
  Medline CASGoogle Scholar
• 45 Yimer G, Ueda N, Habtewold A et al. Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB–HIV infected patients. PLoS ONE 6(12), e27810 (2011).
  Medline CASGoogle Scholar
• 46 Mugusi S, Ngaimisi E, Janabi M et al. 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(7), e40180 (2012).
  Medline CASGoogle Scholar
• 47 ENCORE1 Study Group; Puls R, Amin J, Losso M et al. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet 383(9927), 1474–1482 (2014).
  MedlineGoogle Scholar
• 48 Aklillu E, Dandara C, Bertilsson L, Masimirembwa C. Pharmacogenetics of cytochrome P450s in African populations: clinical and molecular evolutionary implications. In: Pharmacogenomics in Admixed Populations. Suarez-Kurtz G (Ed.). Landes Bioscience, TX, USA, 99–119 (2007).
  Google Scholar