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Drugs

, Volume 78, Issue 16, pp 1741–1750 | Cite as

Dolutegravir/Rilpivirine: A Review in HIV-1 Infection

  • Hannah A. BlairEmail author
Adis Drug Evaluation
  • 209 Downloads

Abstract

Dolutegravir/rilpivirine (Juluca®) is the first two-drug single-tablet regimen (STR) to be approved for the treatment of HIV-1 infection in adults. The fixed-dose STR combines the integrase strand transfer inhibitor dolutegravir with the non-nucleoside reverse transcriptase inhibitor rilpivirine. In two phase III non-inferiority trials (SWORD-1 and SWORD-2) in treatment-experienced patients already virologically suppressed on their current antiretroviral (ART) regimen, switching to once-daily dolutegravir plus rilpivirine maintained virological suppression over 48 weeks. Switching to a two-drug regimen of dolutegravir plus rilpivirine was also associated with high rates of virological suppression in real-world observational studies. Switching to once-daily dolutegravir plus rilpivirine was generally well tolerated and associated with more favourable renal and bone parameters than remaining on the current ART regimen. Longer-term, dolutegravir plus rilpivirine demonstrated durable maintenance of virological suppression and remained generally well tolerated for up to 100 weeks. Thus, dolutegravir/rilpivirine provides a convenient alternative treatment option for some adults with HIV-1 infection and no history of virological failure who are already virologically suppressed on (and wish to switch from) their current ART regimen.

Notes

Acknowledgements

During the peer review process, the manufacturer of dolutegravir/rilpivirine was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Hannah Blair is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 1.
    Bhatti AB, Usman M, Kandi V. Current scenario of HIV/AIDS, treatment options, and major challenges with compliance to antiretroviral therapy. Cureus. 2016;8(3):e515.PubMedPubMedCentralGoogle Scholar
  2. 2.
    European AIDS Clinical Society. Guidelines version 9.0; 2017. http://eacsociety.org. Accessed 29 Oct 2018.
  3. 3.
    US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2018. https://adisinfo.nih.gov/guidelines. Accessed 29 Oct 2018.
  4. 4.
    Boswell R, Foisy MM, Hughes CA. Dolutegravir dual therapy as maintenance treatment in HIV-infected patients: a review. Ann Pharmacother. 2018;52(7):681–9.CrossRefGoogle Scholar
  5. 5.
    de Miguel Buckley R, Montejano R, Stella-Ascariz N, et al. New strategies of ARV: the road to simplification. Curr HIV/AIDS Rep. 2018;15(1):11–9.Google Scholar
  6. 6.
    Soriano V, Fernandez-Montero JV, Benitez-Gutierrez L, et al. Dual antiretroviral therapy for HIV infection. Expert Opin Drug Saf. 2017;16(8):923–32.CrossRefGoogle Scholar
  7. 7.
    Caplan MR, Daar ES, Corado KC. Next generation fixed dose combination pharmacotherapies for treating HIV. Expert Opin Pharmacother. 2018;19(6):589–96.CrossRefGoogle Scholar
  8. 8.
    European Medicines Agency. Juluca 50 mg/25 mg film-coated tablets: EU summary of product characteristics; 2018. http://www.ema.europa.eu. Accessed 29 Oct 2018.
  9. 9.
    ViiV Healthcare. JULUCA (dolutegravir and rilpivirine) tablets, for oral use: US prescribing information; 2017. https://www.fda.gov. Accessed 29 Oct 2018.
  10. 10.
    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.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies. Lancet. 2018;391(10123):839–49.CrossRefGoogle Scholar
  13. 13.
    Mehta R, Wolstenholme A, Di Lullo K, et al. Bioequivalence of a fixed-dose combination tablet of the complete 2-drug regimen dolutegravir and rilpivirine for the treatment of HIV-1 infection. Antimicrob Agents Chemother. 2018;62(9):e00748-18.CrossRefGoogle Scholar
  14. 14.
    Elliot ER, Wang X, Singh S, et al. Increased dolutegravir peak concentrations in people living with HIV aged 60 and over and analysis of sleep quality and cognition. Clin Infect Dis. 2018.  https://doi.org/10.1093/cid/ciy426.CrossRefGoogle Scholar
  15. 15.
    Orkin C, Khuong-Josses MA, Lutz T, et al. Safety and efficacy of DTG + RPV in the phase III SWORD-1 and SWORD-2 studies: 48-week subgroup analysis by baseline third agent class and geographic location [abstract no. P22]. HIV Med. 2018;19(Suppl 2):S28–9.Google Scholar
  16. 16.
    Walmsley S, Richmond GJ, Bredeek F, et al. SWORD-1 and SWORD-2: subgroup analysis of 48-week results by age, race and gender [abstract no. 1382 plus poster]. In: IDWeek; 2017.Google Scholar
  17. 17.
    Oglesby A, Punekar Y, Angelis K, et al. Patient reported outcomes after switching to a 2-drug regimen of dolutegravir + rilpivirine: results from the SWORD-1 and SWORD-2 studies [abstract no. BPD1/2 plus poster]. In: 16th European AIDS conference; 2017.Google Scholar
  18. 18.
    Aboud M, Orkin C, Podzamczer D, et al. Durable suppression 2 years after switch to DTG+RPV 2-drug regimen: SWORD 1 and 2 studies [abstract no. THPEB047]. In: 22nd international AIDS conference; 2018.Google Scholar
  19. 19.
    Revuelta-Herrero JL, Chamorro-de-Vega E, Rodriguez-Gonzalez CG, et al. Effectiveness, safety, and costs of a treatment switch to dolutegravir plus rilpivirine dual therapy in treatment-experienced HIV patients. Ann Pharmacother. 2018;52(1):11–8.CrossRefGoogle Scholar
  20. 20.
    Capetti AF, Cossu MV, Sterrantino G, et al. Dolutegravir plus rilpivirine as a switch option in cART-experienced patients: 96-week data. Ann Pharmacother. 2018;52(8):740–6.CrossRefGoogle Scholar
  21. 21.
    Palacios R, Mayorga M, Gonzalez-Domenech CM, et al. Safety and efficacy of dolutegravir plus rilpivirine in treatment-experienced HIV-infected patients: the DORIVIR study. J Int Assoc Provid AIDS Care. 2018;17:1–4.CrossRefGoogle Scholar
  22. 22.
    Gantner P, Cuzin L, Allavena C, et al. Efficacy and safety of dolutegravir and rilpivirine dual therapy as a simplification strategy: a cohort study. HIV Med. 2017;18(9):704–8.CrossRefGoogle Scholar
  23. 23.
    Diaz A, Casado JL, Dronda F, et al. Dolutegravir plus rilpivirine in suppressed heavily pre-treated HIV-infected patients [abstract no. TUPDB0106 plus poster]. In: 21st international AIDS conference; 2016.Google Scholar
  24. 24.
    Orkin C, Llibre J, Kahl L, et al. Renal, inflammatory and bone biomarkers following switch to the DTG + RPV 2-drug regimen: the SWORD-1 and SWORD-2 studies [abstract no. O37 plus oral presentation]. HIV Med. 2018;19(Suppl 2):S17.Google Scholar
  25. 25.
    US FDA. FDA drug safety communication: FDA to evaluate potential risk of neural tube birth defects with HIV medicine dolutegravir (Juluca, Tivicay, Triumeq); 2018. https://www.fda.gov. Accessed 29 Oct 2018.
  26. 26.
    McComsey GA, Lupo S, Parks D, et al. Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health. AIDS. 2018;32(4):477–85.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Back D. 2-drug regimens in HIV treatment: pharmacological considerations. Germs. 2017;7(3):113–4.CrossRefGoogle Scholar
  28. 28.
    Boyd MA, Cooper DA. Combination ART: are two drugs as good as three? Lancet. 2018;391(10123):817–9.CrossRefGoogle Scholar
  29. 29.
    Aldir I, Horta A, Serrado M. Single-tablet regimens in HIV: does it really make a difference? Curr Med Res Opin. 2014;30(1):89–97.CrossRefGoogle Scholar
  30. 30.
    Arthurs E, Ward T, Darlington O, et al. Dolutegravir and rilpivirine to treat virologically suppressed adults living with HIV-1: a Canadian cost-utility analysis. Value Health. 2018;21(Suppl 1):S9–10.CrossRefGoogle Scholar
  31. 31.
    Sweet DE, Altice FL, Cohen CJ, et al. Cost-effectiveness of single- versus generic multiple-tablet regimens for treatment of HIV-1 infection in the United States. PLoS One. 2016;11(1):e0147821.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

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