Skip to main content
SpringerLink
Log in

Long-Term Efficacy and Safety of Efavirenz Dose Reduction to 200 mg Once Daily in a Caucasian Patient with HIV

  • Case Report
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

A 48-year-old Caucasian male patient presented with severe adverse drug events (ADEs) while being treated with a standard dose (600 mg/day) of efavirenz. The patient’s clinical course was favourable; however, he also described intense nightmares, cramps in his legs and anxiety disturbances that made him highly irritable. Measurement of the patient’s efavirenz plasma concentrations revealed a mean minimum steady-state concentration during a dosage interval (Cmin,ss) of 12.7 mg/L, which was much higher than that recommended for this drug (therapeutic range 1–4 mg/L). Consequently, the dose of efavirenz was reduced to 400 mg/day, which resulted in a decrease in the frequency of ADEs. Subsequent genotype testing showed that the patient was homozygous for both the CYP2B6- G516T (T/T) and CYP2B6- A785G (G/G) alleles; these polymorphisms are associated with reduced enzymatic activity and elevated efavirenz plasma concentrations. Because of this and the fact that the patient’s mean efavirenz Cmin,ss was still high (4.6 mg/L), a second dosage reduction was undertaken, to 200 mg/day. This also resulted in a reduction in ADEs. At present, the patient’s CD4+ levels remain stable, his viral load continues to be undetectable and the mean efavirenz Cmin,ss is within the therapeutic range (2.7 mg/L).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 2008 Jan 29: 1-128 [online]. Available from URL: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf [Accessed 2009 Jul 26]

  2. Blanch J, Martinez E, Rousaud A, et al. Preliminary data of a prospective study on neuropsychiatric side effects after initiation of efavirenz. J Acquir Immune Defic Syndr 2001 Aug 1; 27(4): 336–43

    PubMed  CAS  Google Scholar 

  3. Puzantian T. Central nervous system adverse effects with efavirenz: case report and review. Pharmacotherapy 2002 Jul; 22(7): 930–3

    Article  PubMed  Google Scholar 

  4. U.S. Food and Drug Administration. Sustiva label information, approved 2008 Aug 18 [online]. Available from URL: http://www.fda.gov/cder/foi/label/2008/020972s030,021360s019lbl.pdf [Accessed 2009 Jul 15]

  5. Staszewski S, Morales-Ramirez J, Tashima KT, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. N Engl J Med 1999 Dec 16; 341(25): 1865–73

    Article  PubMed  CAS  Google Scholar 

  6. Fumaz CR, Muñoz-Moreno JA, Moltó J, et al. Long-term neuropsychiatric disorders on efavirenz-based approaches: quality of life, psychologic issues, and adherence. J Acquir Immune Defic Syndr 2005 Apr 15; 38(5): 560–5

    Article  PubMed  Google Scholar 

  7. 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 Jan 5; 15(1): 71–5

    Article  PubMed  CAS  Google Scholar 

  8. Hasse B, Gunthard HF, Bleiber G, et al. Efavirenz intoxication due to slow hepatic metabolism. Clin Infect Dis 2005Feb1; 40(3): e22–3

    Article  PubMed  CAS  Google Scholar 

  9. Núñez M, González de Requeda D, Gallego L, et al. Higher efavirenz plasma levels correlate with development of insomnia. J Acquir Immune Defic Syndr 2001 Dec 1; 28(4): 399–400

    PubMed  Google Scholar 

  10. King J, Aberg JA. Clinical impact of patient population differences and genomic variation in efavirenz therapy. AIDS 2008 Sep 12; 22(14): 1709–17

    Article  PubMed  CAS  Google Scholar 

  11. Takahashi M, Ibe S, Kudaka Y, et al. No observable correlation between central nervous system side effects and EFV plasma concentrations in Japanese HIV type 1-infected patients treated with EFV containing HAART. AIDS Res Hum Retroviruses 2007 Aug; 23(8): 983–7

    Article  PubMed  CAS  Google Scholar 

  12. HIV-Pharmacogenomics [online]. Available from URL: http://www.hiv-pharmacogenomics.org [Accessed 2009 Jul 23]

  13. Csajka C, Marzolini C, Fattinger K, et al. Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 2003 Jan; 73(1): 20–30

    Article  PubMed  CAS  Google Scholar 

  14. Pfister M, Labbe L, Hammer SM, et al. Population pharmacokinetics and pharmacodynamics of efavirenz, nelfinavir and indinavir. Adult AIDS Clinical Trial Group Study 398. Antimicrob Agents Chemother 2003 Jan; 47(1): 130–7

    Article  PubMed  CAS  Google Scholar 

  15. Kappelhoff BS, van Leth F, MacGregor TR, et al. Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir Ther 2005; 10(1): 145–55

    PubMed  CAS  Google Scholar 

  16. 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 Feb; 61(2): 148–54

    Article  PubMed  CAS  Google Scholar 

  17. Arab-Alameddine M, Di Iulio J, Buclin T, et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Swiss HIV Cohort Study. Clin Pharmacol Ther 2009 May; 85(5): 485–94

    Article  PubMed  CAS  Google Scholar 

  18. Cabrera S, Santos D, Valverde MP, et al. Influence of the cytochrome P450 2B6 genotype on population pharmacokinetics of efavirenz in human immunodeficiency virus patients. Antimicrob Agents Chemother 2009 Jul; 53(7): 2791–8

    Article  PubMed  CAS  Google Scholar 

  19. 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 Jul 9; 319(4): 1322–6

    Article  PubMed  CAS  Google Scholar 

  20. 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 Dec 3; 18(18): 2391–400

    PubMed  CAS  Google Scholar 

  21. Rotger M, Colombo S, Furrer H, et al., Swiss HIV Cohort Study. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 2005 Jan; 15(1): 1–5

    Article  PubMed  CAS  Google Scholar 

  22. Gatanaga H, Hayashida T, Tsuchiya K, et al. Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clin Infect Dis 2007 Nov 1; 45(9): 1230–7

    Article  PubMed  CAS  Google Scholar 

  23. Gallego L, Barreiro P, del Río R, et al. Analyzing sleep abnormalities in HIV-infected patients treated with efavirenz. Clin Infect Dis 2004 Feb 1; 38(3): 430–2

    Article  PubMed  CAS  Google Scholar 

  24. Buysse DJ, Reynolds CF, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989 May; 28(2): 193–213

    Article  PubMed  CAS  Google Scholar 

  25. Herrmann C. International experiences with the Hospital Anxiety and Depression Scale: a review of validation data and clinical results. J Psychosom Res 1997 Jan; 42(1): 17–41

    Article  PubMed  CAS  Google Scholar 

  26. Knobel H, Alonso J, Casado JL, et al., GEEMA Study Group. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS 2002 Mar 8; 16(4): 605–13

    Article  PubMed  Google Scholar 

  27. Institut d’Investigacions Biomédiques August Pi i Sunyer, Institut Clínic de Medicina i Dermatología. Interacciones HIV [online]. Available from URL: http://www.interaccioneshiv.com [Accessed 2009 Jul 25]

  28. Torno MS, Witt MD, Saitoh A, et al. Successful use of reduced-dose efavirenz in a patient with human immunodeficiency virus infection: case report and review of the literature. Pharmacotherapy 2008 Jun; 28(6): 782–7

    Article  PubMed  CAS  Google Scholar 

  29. Rodriguez-Novoa S, Barreiro P, Rendón A, et al. 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 May 1; 40(9): 1358–61

    Article  PubMed  CAS  Google Scholar 

  30. Ribaudo HJ, Haas DW, Tierney C, et al. Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis 2006 Feb 1; 42(3): 401–7

    Article  PubMed  CAS  Google Scholar 

  31. Nolan D, Phillips E, Mallal S. Efavirenz and CYP2B6 polymorphism: implications for drug toxicity and resistance. Clin Infect Dis 2006 Feb 1; 42(3): 408–10

    Article  PubMed  CAS  Google Scholar 

  32. Nyakutira C, Röshammar 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 Apr; 64(4): 357–65

    Article  PubMed  CAS  Google Scholar 

  33. Fuertes A, Cabrera SE, Valverde MP, et al. Hyperhidrosis in association with efavirenz. AIDS Patient Care STDs 2009 Mar; 23(3): 143–5

    Article  PubMed  Google Scholar 

  34. Cabrera SE, Valverde MP, Garcïa MJ, et al. Pharmaceutical intervention in the follow-up of antiretroviral therapy. An R Acad Nac Farm 2009; 75(1): 43–62

    Google Scholar 

  35. 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 Feb; 30(1): 60–6

    Article  PubMed  CAS  Google Scholar 

  36. Cabrera SE, Cordero M, Iglesias A, et al. Efavirenz-rifampicin interaction: therapeutic drug monitoring to efavirenz dosage optimization in HIV/TBC patients. AIDS 2008 Nov 30; 22(18): 2549–51

    Article  PubMed  Google Scholar 

  37. ConsejoGeneral de Colegios Oficiales de Farmcëuticos. BOT-Plus [cd-rom]. Ver. 4.4.0. Madrid: 2009

Download references

Acknowledgements

This case report was supported by funding granted by the project FIS PI070714, the Ministry of Health and Consumption of Spain, in the frame of the National Plan of I+D+I 2004–2007. The authors’ work was independent of the funding body. All authors made substantial contributions to the work and meet the criteria for authorship. The authors have no conflicts of interest that are directly relevant to the content of this report.

Author information

Authors and Affiliations

  1. Servicio de Farmacia, Hospital Universitario de Salamanca, Paseo de San Vicente 58-182, 37007, Salamanca, Spain

    Salvador Cabrera Figueroa PhD, Almudena Sánchez Martín, María de la Paz Valverde Merino & Alfonso Domínguez-Gil Hurlé

  2. Pharmacy Institute, University Austral of Chile, Valdivia, Chile

    Salvador Cabrera Figueroa PhD

  3. Infectious Disease Service, University Hospital of Salamanca, Salamanca, Spain

    Alicia Iglesias Gómez & Miguel Cordero Sánchez

Authors
  1. Salvador Cabrera Figueroa PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alicia Iglesias Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Almudena Sánchez Martín
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. María de la Paz Valverde Merino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfonso Domínguez-Gil Hurlé
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miguel Cordero Sánchez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Salvador Cabrera Figueroa PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Figueroa, S.C., Gómez, A.I., Martín, A.S. et al. Long-Term Efficacy and Safety of Efavirenz Dose Reduction to 200 mg Once Daily in a Caucasian Patient with HIV. Clin. Drug Investig. 30, 405–411 (2010). https://doi.org/10.1007/BF03256910

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256910

Keywords

Search

Navigation