Mid-dosing interval efavirenz plasma concentrations in HIV-1-infected children in Rwanda: Treatment efficacy, tolerability, adherence, and the influence of CYP2B6 polymorphisms

Journal of Acquired Immune Deficiency Syndromes

Volumn 60, Issue 4, 2012, Pages 400-404

  Mutwa, Philippe R ^a,b,c   Fillekes, Quirine ^d   Malgaz, Marie ^e   Tuyishimire, Diane ^a,c,f   Van De Kraats, Rianne ^d   Boer, Kimberly R ^a,c,g   Burger, David M ^d   Van Schaik, Ron H N ^h   Muganga, Narcisse ^a   Geelen, Sibyl P M ^a,c,e  

^a Centre Hospitalier Universitaire de Kigali   (Rwanda)

^b Academic Medical Centre   (Rwanda)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^f Treatment and Research on HIV/AIDS Centre (TRAC plus)   (Rwanda)

^g ROYAL TROPICAL INSTITUTE   (Netherlands)

^h ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

antiretroviral treatment; children; CYP2B6; efavirenz; pharmacogenetics; Rwanda

Indexed keywords

CYTOCHROME P450 2B6; EFAVIRENZ; LAMIVUDINE; STAVUDINE; TENOFOVIR; ZIDOVUDINE;

ADOLESCENT; ARTICLE; CENTRAL NERVOUS SYSTEM DISEASE; CHILD; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG TOLERABILITY; DRUG TREATMENT FAILURE; FEMALE; GENE FREQUENCY; GENETIC POLYMORPHISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MAJOR CLINICAL STUDY; MALE; PATIENT COMPLIANCE; PHARMACOGENETICS; PRIORITY JOURNAL; RWANDA; SKIN DISEASE; TREATMENT OUTCOME;

ADOLESCENT; ANTI-HIV AGENTS; ARYL HYDROCARBON HYDROXYLASES; BENZOXAZINES; CHILD; CHILD, PRESCHOOL; FEMALE; GENE FREQUENCY; HIV INFECTIONS; HIV-1; HUMANS; MALE; OXIDOREDUCTASES, N-DEMETHYLATING; PLASMA; POLYMORPHISM, GENETIC; RWANDA; TREATMENT OUTCOME; VIRAL LOAD;

EID: 84864287061     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0b013e3182569f57     Document Type: Article

References (31)

1. Rwanda Ministry of Health. Guidelines for the provision of comprehensive care to persons infected by HIV in Rwanda. 2009;93-98.
2. WHO. Antiretroviral therapy of HIV infection in infants and children: towards universal access: recommendations for a public health approach: 2010 revision. Available at: http://www.who.int/hiv/pub/guidelines/art/en/. Accessed June, 2011.
3. Scherpbier HJ, Bekker V, Pajkrt D, et al. Once-daily highly active antiretroviral therapy for HIV-infected children: safety and efficacy of an efavirenz-containing regimen. Pediatrics. 2007;119:e705-e715. (Pubitemid 46407545)
4. Teglas JP, Quartier P, Treluyer JM, et al. Tolerance of efavirenz in children. AIDS. 2001;15:241-243. (Pubitemid 32142300)
5. European Medicines Agency. Sustiva tablets; summary of product characteristics. Available at: http://www.ema.europa.eu/docs/en-GB/document- library/EPAR-Product-Information/human/000249/WC500058311.pdf. Accessed June 15, 2012.
6. Marzolini C, Telenti A, Decosterd LA, et al. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS. 2001;15:71-75. (Pubitemid 32055781)
7. Ren Y, Nuttall JJ, Egbers C, et al. High prevalence of subtherapeutic plasma concentrations of efavirenz in children. J Acquir Immune Defic Syndr. 2007;45:133-136. (Pubitemid 46869804)
8. Brundage RC, Yong FH, Fenton T, et al. Intrapatient variability of efavirenz concentrations as a predictor of virologic response to antiretroviral therapy. Antimicrob Agents Chemother. 2004;48:979-984. (Pubitemid 38280352)
9. Fillekes Q, Natukunda E, Balungi J, et al. Pediatric underdosing of efavirenz: a pharmacokinetic study in Uganda. J Acquir Immune Defic Syndr. 2011;58:392-398.
10. Hirt D, Urien S, Olivier M, et al. Is the recommended dose of efavirenz optimal in young West African human immunodeficiency virus-infected children? Antimicrob Agents Chemother. 2009;53:4407-4413.
11. Pereira SA, Branco T, Caixas U, et al. Intra-individual variability in efavirenz plasma concentrations supports therapeutic drug monitoring based on quarterly sampling in the first year of therapy. Ther Drug Monit. 2008;30:60-66. (Pubitemid 351161100)
12. ter Heine R, Scherpbier HJ, Crommentuyn KM, et al. A pharmacokinetic and pharmacogenetic study of efavirenz in children: dosing guidelines can result in subtherapeutic concentrations. Antivir Ther. 2008;13:779-787.
13. von HN, Koenigs C, Elanjikal S, et al. Need for therapeutic drug monitoring in HIV-1 infected children receiving efavirenz doses according to international guidelines. Eur J Med Res. 2006;11:377-380. (Pubitemid 44575697)
14. 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. 2006;61:148-154. (Pubitemid 43382608)
15. Viljoen M, Gous H, Kruger HS, et al. Efavirenz plasma concentrations at 1, 3, and 6 months post-antiretroviral therapy initiation in HIV type 1-infected South African children. AIDS Res Hum Retroviruses. 2010;26:613-619.
16. Haas DW, Gebretsadik T, Mayo G, et al. Associations between CYP2B6 polymorphisms and pharmacokinetics after a single dose of nevirapine or efavirenz in African Americans. J Infect Dis. 2009;199:872-880.
17. Jittamala P, Puthanakit T, Chaiinseeard S, et al. Predictors of virologic failure and genotypic resistance mutation patterns in Thai children receiving non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy. Pediatr Infect Dis J. 2009;28:826-830.
18. Lowenhaupt EA, Matson K, Qureishi B, et al. Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. Clin Infect Dis. 2007;45:e128-e130. (Pubitemid 351411927)
19. Saitoh A, Fletcher CV, Brundage R, et al. Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. J Acquir Immune Defic Syndr. 2007;45:280-285. (Pubitemid 47012374)
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. 2009;68:690-699.
21. 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.
22. WHO. Antiretroviral therapy of HIV infection in infants and children: towards universal access. 2006. Available at: http://www.who.int/hiv/-pub/ guidelines/WHOpaediatric.pdf. Accessed June 2011.
23. Aarnoutse RE, Schapiro JM, Boucher CA, et al. Therapeutic drug monitoring: an aid to optimising response to antiretroviral drugs? Drugs. 2003;63:741-753. (Pubitemid 36428444)
24. Verweij-van Wissen CP, Aarnoutse RE, Burger DM. Simultaneous determination of the HIV nucleoside analogue reverse transcriptase inhibitors lamivudine, didanosine, stavudine, zidovudine and abacavir in human plasma by reversed phase high performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;816: 121-129. (Pubitemid 40143498)
25. Wintergerst U, Hoffmann F, Jansson A, et al. Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIVinfected children. J Antimicrob Chemother. 2008;61:1336-1339. (Pubitemid 351753604)
26. Barrett JS, Joshi AS, Chai M, et al. Population pharmacokinetic meta-analysis with efavirenz. Int J Clin Pharmacol Ther. 2002;40: 507-519. (Pubitemid 35331935)
27. Haas DW, Smeaton LM, Shafer RW, et al. Pharmacogenetics of longterm responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an Adult AIDS Clinical Trials Group Study. J Infect Dis. 2005;192:1931-1942. (Pubitemid 41681891)
28. 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.
29. Arenaz I, Vicente J, Fanlo A, et al. Haplotype structure and allele frequencies of CYP2B6 in Spaniards and Central Americans. Fundam Clin Pharmacol. 2010;24:247-253.
30. Desta Z, Saussele T, Ward B, et al. Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics. 2007;8: 547-558. (Pubitemid 46947859)
31. Stohr W, Back D, Dunn D, et al. Factors influencing efavirenz and nevirapine plasma concentration: effect of ethnicity, weight and co-medication. Antivir Ther. 2008;13:675-685.