Drugs

, Volume 63, Issue 11, pp 1089–1098 | Cite as

Lamivudine/Zidovudine/Abacavir

Triple Combination Tablet
Adis Drug Profile

Abstract

  • ▴ The triple combination tablet containing lamivudine (150mg), zidovudine (300mg) and abacavir (300mg, as abacavir sulfate) is a new formulation of three nucleoside analogue reverse transcriptase inhibitors.

  • ▴ Two studies in treatment-naive patients (one double-blind, one nonblind) have reported that lamivudine/zidovudine (dual combination tablet) plus abacavir showed efficacy similar to that of lamivudine/zidovudine plus indinavir. In both studies, similar numbers of patients in each treatment group had plasma HIV RNA levels <400 copies/mL at week 48 (51% vs 51% and 64% vs 50%).

  • ▴ In treatment-experienced patients with baseline plasma HIV RNA levels <50 copies/mL, switching to lamivudine/zidovudine/abacavir (triple combination tablet) was as effective as remaining on highly active antiretroviral treatment (mainly protease inhibitor [PI]-based). Virological failure, the primary endpoint, defined as two consecutive plasma HIV RNA values >400 copies/mL, was reported in 22% of patients in both treatment groups at week 48.

  • ▴ Treatment-naive patients receiving lamivudine/zidovudine/abacavir combination therapy experienced several adverse events, including nausea, malaise/fatigue and vomiting.

Keywords

Lamivudine Zidovudine Abacavir Virological Failure Amprenavir 

References

  1. 1.
    Fauci AS. Infectious diseases: considerations for the 21st century. Clin Infect Dis 2001 Mar 1; 32(5): 675–85PubMedCrossRefGoogle Scholar
  2. 2.
    Fauci AS. The AIDS epidemic: considerations for the 21st century. N Engl J Med 1999 Sep 30; 341(14): 1046–50PubMedCrossRefGoogle Scholar
  3. 3.
    Panel on Clinical Practices for treatment of HIV infection. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents [online]. Available from URL: http://www.hivatis.org [Accessed 2002 Feb 4]
  4. 4.
    Carpenter CCJ, Cooper DA, Fischl MA, et al. Antiretroviral therapy in adults: updated recommendations of the International AIDS Society —USA panel. 2000 Jan 19; 283: 381–90Google Scholar
  5. 5.
    Gazzard B, Moyle G, BHIVA Guidelines Writing Committee. 1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals. Lancet 1998 Jul 25; 352: 314–6PubMedCrossRefGoogle Scholar
  6. 6.
    Plosker GL, Noble S. Indinavir: a review of its use in the management of HIV infection. Drugs 1999 Dec; 58: 1165–203PubMedCrossRefGoogle Scholar
  7. 7.
    Rutherford GW, Feldman KA, Kennedy GE. Three- or four-versus two-drug antiretroviral maintenance regimens for HIV infection. Cochrane Database Syst Rev 2000; (2): CD002037Google Scholar
  8. 8.
    Trizivir® (abacavir sulphate, lamivudine and zidovudine) tablets. US product information. Research Triangle Park (NC): GlaxoSmithKline, 2001 MayGoogle Scholar
  9. 9.
    Hervey PS, Perry CM. Abacavir: a review of its clinical potential in patients with HIV infection. Drugs 2000 Aug; 60(2): 447–79PubMedCrossRefGoogle Scholar
  10. 10.
    Perry CM, Faulds D. Lamivudine: a review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs 1997 Apr; 53(4): 657–80PubMedCrossRefGoogle Scholar
  11. 11.
    Weller S, Radomski KM, Lou Y, et al. Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother 2000 Aug; 44(8): 2052–60PubMedCrossRefGoogle Scholar
  12. 12.
    Wilde MI, Langtry HD. Zidovudine: an update of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 1993 Sep; 46(3): 515–78PubMedCrossRefGoogle Scholar
  13. 13.
    Porche D. Abacavir sulfate, lamivudine, and zidovudine (Trizivir). J Assoc Nurses AIDS Care 2001 Nov-2001 31; 12(6): 88–90PubMedCrossRefGoogle Scholar
  14. 14.
    Miller V, Larder B. Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. Antivir Ther 2001; 6 Suppl. 3: 25–44Google Scholar
  15. 15.
    Walter H, Schmidt B, Werwein M, et al. Prediction of abacavir resistance from genotypic data: impact of zidovudine and lamivudine resistance in vitro and in vivo. Antimicrob Agents Chemother 2002 Jan; 46(1): 89–94PubMedCrossRefGoogle Scholar
  16. 16.
    Miller V, Ait-Khaled M, Stone C, et al. HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. AIDS 2000 Jan 28; 14(2): 163–71PubMedCrossRefGoogle Scholar
  17. 17.
    Lanier ER, Hellmann H, Scott J, et al. Determination of a clinically relevant phenotypic resistance “cutoff” for abacavir using the PhenoSense Assay [abstract]. 8th Conf Retroviruses Opportun Infect; 2001 Feb 4–8; Chicago (IL)Google Scholar
  18. 18.
    Melby T, Tortell S, Thorborn D, et al. Time to appearance of NRTI associated mutations and response to subsequente therapy for patients on failing ABC/COM (CNA3005) [abstract no. 448]. 8th Conf Retroviruses Opportun Infect; 2001 Feb 4–8; Chicago (IL), 5Google Scholar
  19. 19.
    Staszewski S, Keiser P, Montaner J, et al. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral-naive HIV-infected adults: a randomized equivalence trial. JAMA 2001 Mar 7; 285(9): 1155–63PubMedCrossRefGoogle Scholar
  20. 20.
    Ait-Khaled M, Rakik A, Griffin P, et al. Viral rebound during 48 weeks of abacavir/lamivudine/zidovudine combination therapy in antiretroviral-naive subjects is infrequent with emergent virus showing a limited number of NRTI resistance mutations [abstract no. 76]. Antiviral Ther 1999 Jun; 4 Suppl. 1: 52Google Scholar
  21. 21.
    Opravil M, Hirschel B, Lazzarin A, et al. A randomized trial of simplified maintenance therapy with abacavir, lamivudine, and zidovudine in human immunodeficiency virus infection. J Infect Dis 2002 May 1; 185(9): 1251–60PubMedCrossRefGoogle Scholar
  22. 22.
    Katlama C, Fenske S, Gazzard B, et al. Switch to Trizivir versus continued HAART provides equivalent HIV-1 RNA suppression at 48 weeks (TRIZAL-AZL30002) [abstract no. I-671]. 41st ICAAC; 2001 Dec 16–19; Chicago (IL), 324Google Scholar
  23. 23.
    Lafeuillade A, Mamet JP, Chéret A, et al. Comparison of the metabolic disorders and clinical lipodystrophy 48 weeks after switching from highly active antiretroviral therapy to Trizivir versus continued highly antiretroviral therapy (TRIZAL: AZL30002) [abstract no. 28]. Antiviral Ther 2001 Oct; 6 Suppl. 4: 20Google Scholar
  24. 24.
    Walli R, Huster K, Goebel FD. Effect of switching from protease inhibitors to abacavir on insulin sensitivity and fasting lipids: 12-month follow-up [abstract no. P43]. Antiviral Ther 2000 Sep; 5 Suppl. 5: 48Google Scholar
  25. 25.
    de Truchis P, Force G, Welker Y, et al. Efficacy and safety of a quadruple combination combivir + abacavir + efavirenz regimen in antiretroviral treatment-naive HIV-1-infected adults: La Francilienne. J Acquir Immune Defic Syndr 2002; 31: 178–82PubMedCrossRefGoogle Scholar
  26. 26.
    Cremieux AC, Katlama C, Gillotin C, et al. A comparison of the steady-state pharmacokinetics and safety of abacavir, lamivudine, and zidovudine taken as a triple combination tablet and as abacavir plus a lamivudine-zidovudine double combination tablet by HIV-1-infected adults. Pharmacotherapy 2001 Apr: 21(4): 424–30PubMedCrossRefGoogle Scholar
  27. 27.
    Yuen GJ, Lou Y, Thompson NF, et al. Abacavir/lamivudine/ zidovudine as a combined formulation tablet: bioequivalence compared with each component administered concurrently and the effect of food on absorption. J Clin Pharmacol 2001 Mar: 41(3): 277–88PubMedCrossRefGoogle Scholar
  28. 28.
    Vibhagool A, Cahn P, Schechter M, et al. Abacavir/combivir is comparable to indinavir/combivir in HIV-1 infected antiretroviral therapy naive adults: preliminary results of a 48-week open label study (CNA3014) [abstract no 63]. 1st International Aids Society Conference; 2001 Jul 8–11; Buenos Aires, 102Google Scholar
  29. 29.
    Kirkland LR, Fischl MA, Tashima KT, et al. Response to lamivudine-zidovudine plus abacavir twice daily in antiretroviral-naive, incarcerated patients with HIV infection taking directly observed treatment. Clin Infect Dis 2002 Feb 15; 34(4): 511–8PubMedCrossRefGoogle Scholar
  30. 30.
    Rozenbaum W, Katlama C, Massip P, et al. Treatment intensification with abacavir in HIV-1 infected adults with previous 3TC/ZDV antiretroviral treatment; 48 week results (CNAB3009) [abstract plus poster]. 7th European Conference on Clinical Aspects and Treatment of HIV Infection; 1999 Oct 23; Lisbon, 91Google Scholar
  31. 31.
    Matheron S, Vezinet BV, Katlama C, et al. 48 week results of the CNAF3007/Ecureuil open label study: efficacy and safety of the triple nucleoside combination combivir/abacabir versus combivir/nelfinavir as first-line antiretroviral therapy in HIV-1 infected adults [abstract no. P15]. AIDS 2000 Oct; 14 Suppl. 2: S21Google Scholar
  32. 32.
    Clumeck N, Goebel F, Rozenbaum W, et al. Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA. AIDS 2001 Aug 17; 15(12): 1517–26PubMedCrossRefGoogle Scholar
  33. 33.
    Henry K, Wallace RJ, Bellman PC, et al. Twice-daily triple nucleoside intensification treatment with lamivudine-zidovudine plus abacavir sustains suppression of human immunodeficiency virus type 1: results of the TARGET Study. J Infect Dis 2001 Feb 15; 183(4): 571–8PubMedCrossRefGoogle Scholar
  34. 34.
    Kost RG, Hurley A, Zhang L, et al. Open-label phase II trial of amprenavir, abacavir, and fixed-dose zidovudine/lamivudine in newly and chronically HIV-1-infected patients. J Acquir Immune Defic Syndr 2001 Apr 1; 26(4): 332–9PubMedGoogle Scholar
  35. 35.
    Trizivir® (abacavir sulphate, lamivudine and zidovudine) tablets. Product monograph. Research Triangle Park (NC): GlaxoSmithKline, 2002 JunGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations