Skip to main content
SpringerLink
Log in

Abacavir/Dolutegravir/Lamivudine Single-Tablet Regimen: A Review of Its Use in HIV-1 Infection

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

An Erratum to this article was published on 14 March 2015

Abstract

A fixed-dose, single-tablet regimen comprising the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine (abacavir/dolutegravir/lamivudine; Triumeq®) is now available for the treatment of HIV-1 infection. In a randomized, double-blind, phase III trial in antiretroviral therapy (ART)-naive adults (SINGLE), once-daily dolutegravir plus abacavir/lamivudine had noninferior efficacy to once-daily efavirenz/tenofovir disoproxil fumarate (tenofovir DF)/emtricitabine with regard to establishing and sustaining virological suppression over 144 weeks, and subsequent superiority testing significantly favoured dolutegravir plus abacavir/lamivudine. This outcome was predominantly driven by more favourable rates of discontinuation due to adverse events versus the efavirenz/tenofovir DF/emtricitabine group. These data were generally supported by findings from other phase III trials in ART-naive adults receiving dolutegravir plus either abacavir/lamivudine or tenofovir DF/emtricitabine (SPRING-2 and FLAMINGO). Dolutegravir plus abacavir/lamivudine is generally well tolerated, with a tolerability profile that appears to be more favourable than efavirenz/tenofovir DF/emtricitabine. In the SINGLE trial, there were no major treatment-emergent INSTI or NRTI resistance-associated mutations in dolutegravir plus abacavir/lamivudine recipients with protocol-defined virological failure, indicating a high genetic barrier to resistance. Thus, triple combination therapy with abacavir, dolutegravir and lamivudine is an effective, generally well tolerated option for the management of HIV-1 infection, with the convenient once-daily fixed-dose tablet providing the first single-tablet regimen option without tenofovir DF.

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

Fig. 1

Similar content being viewed by others

References

  1. US 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. 2014. http://aidsinfo.nih.gov/guidelines. Accessed 9 Feb 2015.

  2. Williams DI, Churchill D, Anderson J, et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012 (updated November 2013). HIV Med. 2014;15(Suppl 1):1–85.

    CAS  Google Scholar 

  3. Günthard HF, Aberg JA, Eron JJ, et al. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA. 2014;312(4):410–25.

    Article  PubMed  Google Scholar 

  4. EACS: European AIDS Clinical Society. Guidelines version 7.02. 2014. http://eacsociety.org. Accessed 9 Feb 2015.

  5. Thompson MA, Mugavero MJ, Amico KR, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel. Ann Intern Med. 2012;156(11):817–33, W-284–94.

  6. Kauf TL, Davis KL, Earnshaw SR, et al. Spillover adherence effects of fixed-dose combination HIV therapy. Patient Prefer Adherence. 2012;6:155–64.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Llibre JM, Clotet B. Once-daily single-tablet regimens: a long and winding road to excellence in antiretroviral treatment. AIDS Rev. 2012;14(3):168–78.

    PubMed  Google Scholar 

  8. Astuti N, Maggiolo F. Single-tablet regimens in HIV therapy. Infect Dis Ther. 2014;3(1):1–17.

    Article  PubMed Central  PubMed  Google Scholar 

  9. ViiV Healthcare UK Ltd. Triumeq 50 mg/600 mg/300 mg film-coated tablets: EU summary of product characteristics. 2014. http://www.ema.europe.eu. Accessed 9 Feb 2015.

  10. ViiV Healthcare. Triumeq (abacavir, dolutegravir, and lamivudine) tablets, for oral use: US prescribing information. 2014. http://www.fda.gov. Accessed 9 Feb 2015.

  11. ViiV Healthcare ULC. Triumeq™ (dolutegravir, abacavir, and lamivudine tablets): Canada product monograph. 2014. http://webprod5.hc-sc.gc.ca. Accessed 9 Feb 2015.

  12. McCormack PL. Dolutegravir: a review of its use in the management of HIV-1 infection in adolescents and adults. Drugs. 2014;74(11):1241–52.

    Article  CAS  PubMed  Google Scholar 

  13. Hare S, Smith SJ, Métifiot M, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011;80(4):565–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Kobayashi M, Yoshinaga T, Seki T, et al. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011;55(2):813–21.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Dando T, Scott L. Abacavir plus lamivudine. Drugs. 2005;65(2):285–302.

    Article  CAS  PubMed  Google Scholar 

  16. Pollicita M, Surdo M, Di Santo F, et al. Comparative replication capacity of raltegravir-resistant strains and antiviral activity of the new-generation integrase inhibitor dolutegravir in human primary macrophages and lymphocytes. J Antimicrob Chemother. 2014;69(9):2412–9.

    Article  CAS  PubMed  Google Scholar 

  17. ViiV Healthcare. Epivir (lamivudine) tablets and oral solution: US prescribing information. 2011. http://www.fda.gov. Accessed 9 Feb 2015.

  18. ViiV Healthcare. Ziagen (abacavir sulfate) tablets, for oral use and oral solution: US prescribing information. 2013. http://www.fda.gov. Accessed 9 Feb 2015.

  19. Walmsley SL, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection [plus supplementary appendix]. N Engl J Med. 2013;369(19):1807–18.

    Article  CAS  PubMed  Google Scholar 

  20. Walmsley S, Berenguer J, Khuong-Josses MA. Dolutegravir regimen statistically superior to tenofovir/emtricitabine/efavirenz: 96-wk data from the SINGLE study (ING114467) [abstract no. 543 plus poster]. Top Antivir Med. 2014;22(e-1):261–2.

    Google Scholar 

  21. Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13(11):927–35.

    Article  CAS  PubMed  Google Scholar 

  22. Cahn P, Pozniak AL, Mingrone H, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700–8.

    Article  CAS  PubMed  Google Scholar 

  23. Clotet B, Feinberg J, van Lunzen J, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014;383(9936):2222–31.

    Article  CAS  PubMed  Google Scholar 

  24. Cooper DA, Steigbigel RT, Gatell JM, et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008;359(4):355–65.

    Article  CAS  PubMed  Google Scholar 

  25. Garrido C, Villacian J, Zahonero N, et al. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob Agents Chemother. 2012;56(6):2873–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Hightower KE, Wang R, DeAnda F, et al. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob Agents Chemother. 2011;55(10):4552–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Canducci F, Ceresola ER, Boeri E, et al. Cross-resistance profile of the novel integrase inhibitor dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir. J Infect Dis. 2011;204(11):1811–5.

    Article  CAS  PubMed  Google Scholar 

  28. Huang W, Frantzell A, Whitcomb JM. Impact of raltegravir/elvitegravir selected mutations on dolutegravir cross-resistance [abstract no. 595]. Top Antivir Med. 2014;22(e-1):292–3.

    Google Scholar 

  29. Fourati S, Charpentier C, Amiel C, et al. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients. J Antimicrob Chemother. 2015. doi:10.1093/jac/dku535.

    Google Scholar 

  30. Castagna A, Maggiolo F, Penco G, et al. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J Infect Dis. 2014;210(3):354–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Malet I, Gimferrer Arriaga L, Artese A, et al. New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. J Antimicrob Chemother. 2014;69(8):2118–22.

    Article  CAS  PubMed  Google Scholar 

  32. ViiV Healthcare. Epzicom (abacavir sulfate and lamivudine) tablets, for oral use: US prescribing information. 2012. http://www.fda.gov. Accessed 9 Feb 2015.

  33. Wensing AM, Calvez V, Gunthard HF, et al. 2014 Update of the drug resistance mutations in HIV-1. Top Antivir Med. 2014;22(3):642–50.

    PubMed  Google Scholar 

  34. Chen S, Min SS, Peppercorn A, et al. Effect of a single supratherapeutic dose of dolutegravir on cardiac repolarization. Pharmacotherapy. 2012;32(4):333–9.

    Article  CAS  PubMed  Google Scholar 

  35. Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol. 2013;75(4):990–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Curran A, Martinez E, Podzamczer D, et al. Changes in body composition and mitochondrial DNA in HIV-1-infected patients switching to fixed-dose abacavir/lamivudine or tenofovir/emtricitabine: a substudy of the BICOMBO trial. Antivir Ther. 2012;17(4):711–8.

    Article  CAS  PubMed  Google Scholar 

  37. Yazdanpanah Y, Khuong-Josses M, Hocqueloux L, et al. 48 week bone marker changes with dolutegravir (DTG) plus abacavir/lamivudine (ABC/3TC) vs. tenofovir/emtricitabine/efavirenz (EFV/TDF/FTC): the SINGLE trial [abstract no. P72]. BMC Infect Dis. 2014;14(Suppl 2):30.

    Article  Google Scholar 

  38. Vannappagari V, Koram N, Albano J, et al. Abacavir and lamivudine exposures during pregnancy and non-defect adverse pregnancy outcomes: data from the Antiretroviral Pregnancy Registry. J Acquir Immune Defic Syndr. 2014. doi:10.1097/QAI.0000000000000465.

  39. Weller S, Chen S, Borland J, et al. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food. J Acquir Immune Defic Syndr. 2014;66(4):393–8.

    Article  CAS  PubMed  Google Scholar 

  40. Letendre SL, Mills AM, Tashima KT, et al. ING116070: a study of the pharmacokinetics and antiviral activity of dolutegravir in cerebrospinal fluid in HIV-1-infected, antiretroviral therapy-naive subjects. Clin Infect Dis. 2014;59(7):1032–7.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Capparelli EV, Letendre SL, Ellis RJ, et al. Population pharmacokinetics of abacavir in plasma and cerebrospinal fluid. Antimicrob Agents Chemother. 2005;49(6):2504–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Adams JL, Patterson KB, Prince HM, et al. Single and multiple dose pharmacokinetics of dolutegravir in the genital tract of HIV-negative women. Antivir Ther. 2013;18(8):1005–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Greener BN, Patterson KB, Prince HMA, et al. Dolutegravir pharmacokinetics in the genital tract and colorectum of HIV-negative men after single and multiple dosing. J Acquir Immune Defic Syndr. 2013;64(1):39–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Castellino S, Moss L, Wagner D, et al. Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother. 2013;57(8):3536–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Heald AE, Hsyu PH, Yuen GJ, et al. Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother. 1996;40(6):1514–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Chen S, St Jean P, Borland J, et al. Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics. Pharmacogenomics. 2014;15(1):9–16.

    Article  CAS  PubMed  Google Scholar 

  47. Pappa K, Baumgarten A, Felizarta F, et al. Dolutegravir (DTG) + abacavir/lamivudine once daily superior to tenofovir/emtricitabine/efavirenz in treatment naive HIV subjects: 144-week results from SINGLE (ING114467) [abstract no. H-647a]. In: 54th Interscience Conference on Antimicrobial Agents and Chemotherapy. 2014.

  48. Raffi F, Rachlis A, Stellbrink H-J, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381(9868):735–43.

    Article  CAS  PubMed  Google Scholar 

  49. Molina JM, Clotet B, van Lunzen J, et al. Once-daily dolutegravir is superior to once-daily darunavir/ritonavir in treatment-naive HIV-1-positive individuals: 96 week results from FLAMINGO [abstract no. O153]. J Int AIDS Soc. 2014;17(Suppl 3):19490.

    PubMed Central  PubMed  Google Scholar 

  50. Raffi F, Rachlis A, Brinson C, et al. Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV-infected individuals in three randomized trials. AIDS. 2015;29(2):167–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. NAM Publications. Risk of cardiovascular disease. 2011. http://www.aidsmap.com. Accessed 9 Feb 2015.

  52. Rogatto F, Bouee S, Jeanbat V, et al. An indirect comparison of efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir and dolutegravir + abacavir/lamivudine [abstract no. P247]. J Int AIDS Soc. 2014;17(Suppl 3):19779.

    PubMed Central  PubMed  Google Scholar 

  53. Gilead Sciences Ltd. Stribild 150 mg/150 mg/200 mg/245 mg film-coated tablets: EU summary of product characteristics. 2013. http://www.ema.europe.eu. Accessed 9 Feb 2015.

  54. Cohen CJ, Meyers JL, Davis KL. Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US medicaid population with HIV. BMJ Open. 2013;3(8). doi:10.1136/bmjopen-2013-003028.

  55. Colombo GL, Castagna A, Di Matteo S, et al. Cost analysis of initial highly active antiretroviral therapy regimens for managing human immunodeficiency virus-infected patients according to clinical practice in a hospital setting. Ther Clin Risk Manag. 2014;10:9–15.

    PubMed Central  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit. Sarah Greig and Emma Deeks are salaried employees of Adis/Springer.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Sarah L. Greig & Emma D. Deeks

Authors
  1. Sarah L. Greig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emma D. Deeks
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah L. Greig.

Additional information

The manuscript was reviewed by: N. Clumeck, Centre Hospitalier Universitaire Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; F. Gutierrez, Hospital General de Elche, University Miguel Hernández, Alicante, Spain; L. Hocqueloux, Centre Hospitalier Régional d′Orléans-La Source, Orléans, France; F. Maggiolo, AO Papa Giovanni XXIII, Bergamo, France; U. Sandovsky, University of Nebraska Medical Center, Omaha, NB, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Greig, S.L., Deeks, E.D. Abacavir/Dolutegravir/Lamivudine Single-Tablet Regimen: A Review of Its Use in HIV-1 Infection. Drugs 75, 503–514 (2015). https://doi.org/10.1007/s40265-015-0361-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0361-6

Keywords

Search

Navigation