Display options
Cite
Crutchley RD, Guduru RC, Cheng AM. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. HIV AIDS (Auckl). 2016;8:47-65doi: 10.2147/HIV.S99063.
Crutchley, R. D., Guduru, R. C., & Cheng, A. M. (2016). Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. HIV/AIDS (Auckland, N.Z.), 847-65. https://doi.org/10.2147/HIV.S99063
Crutchley, Rustin D, et al. "Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection." HIV/AIDS (Auckland, N.Z.) vol. 8 (2016): 47-65. doi: https://doi.org/10.2147/HIV.S99063
Crutchley RD, Guduru RC, Cheng AM. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. HIV AIDS (Auckl). 2016 Mar 09;8:47-65. doi: 10.2147/HIV.S99063. eCollection 2016. PMID: 27022304; PMCID: PMC4790521.
Copy Download .nbib Format: NLM
Share it on

HIV AIDS (Auckl). 2016 Mar 09;8:47-65. doi: 10.2147/HIV.S99063. eCollection 2016.

Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection.

HIV/AIDS (Auckland, N.Z.)

Rustin D Crutchley, Rakesh C Guduru, Amy M Cheng

Affiliations

  1. Department of Pharmacy Practice and Translational Research, College of Pharmacy, University of Houston, TX, USA.
  2. CompanionDX, Houston, TX, USA.

PMID: 27022304 PMCID: PMC4790521 DOI: 10.2147/HIV.S99063

Abstract

Atazanavir/cobicistat (ATV/c) and darunavir/cobicistat (DRV/c) are newly approved once daily fixed-dose protease inhibitor combinations for the treatment of HIV-1 infection. Studies in healthy volunteers have established bioequivalence between cobicistat and ritonavir as pharmacoenhancers of both atazanavir (ATV) and darunavir (DRV). In addition, two randomized clinical trials (one Phase II and one Phase III noninferiority trial with a 144-week followup period) demonstrated that cobicistat had sustainable and comparable efficacy and safety to ritonavir as a pharmacoenhancer of ATV through 144 weeks of treatment in HIV-1-infected patients. Furthermore, one Phase III, open-label, single-arm, clinical trial reflected virologic and immunologic responses and safety outcomes consistent with prior published data for DRV/ritonavir 800/100 mg once daily, supporting the use of DRV/c 800/150 mg once daily for future treatment of treatment-naïve and -experienced HIV-1-infected patients with no DRV resistance-associated mutations. Low rates of virologic failure secondary to resistance to antiretroviral regimens were present in these clinical studies. Most notable adverse events in the ATV studies were hyperbilirubinemia and in the DRV study rash. Small increases in serum creatinine and minimally reduced estimated glomerular filtration rate Cockcroft-Gault calculation (eGFRCG) were observed in ATV/c and DRV/c clinical studies consistent with other studies evaluating elvitegravir/cobicistat/tenofovir/emtricitabine for the treatment of HIV-1 infection. These renal parameter changes occurred acutely in the first few weeks and plateaued off for the remaining study periods and are not necessarily clinically relevant. Cobicistat has numerous advantages compared to ritonavir such as fewer drug-drug interactions, being devoid of anti-HIV-1 activity, as well as it has better solubility affording coformulation with other antiretrovirals as simplified fixed-dose combinations. Overall, the recent approval of ATV/c and DRV/c offers HIV patients opportunities for improved adherence to lifelong treatment. Future studies are warranted to determine the efficacy and safety of ATV/c and DRV/c in treatment-experienced patients.

Keywords: HIV protease inhibitors; atazanavir; cobicistat; darunavir; treatment simplification

References

  1. AIDS. 2009 Jul 31;23(12):1547-56 - PubMed
  2. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):e118-20 - PubMed
  3. Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):427-35 - PubMed
  4. Ann Intern Med. 2014 Oct 7;161(7):461-71 - PubMed
  5. J Acquir Immune Defic Syndr. 2009 Apr 1;50(4):367-74 - PubMed
  6. HIV Clin Trials. 2014 Nov-Dec;15(6):269-73 - PubMed
  7. Lancet. 2012 Jun 30;379(9835):2429-38 - PubMed
  8. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):338-40 - PubMed
  9. AIDS Clin Care. 2008 Apr;20(4):28 - PubMed
  10. AIDS Rev. 2014 Jan-Mar;16(1):35-42 - PubMed
  11. J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19537 - PubMed
  12. Clin Interv Aging. 2013;8:749-63 - PubMed
  13. Kidney Int. 2014 Aug;86(2):350-7 - PubMed
  14. J Acquir Immune Defic Syndr. 2006 Oct 1;43(2):153-60 - PubMed
  15. Ann Pharmacother. 2012 Dec;46(12):1671-7 - PubMed
  16. J Lab Clin Med. 1984 Dec;104(6):955-61 - PubMed
  17. Drugs. 2014 Jan;74(1):75-97 - PubMed
  18. Lancet. 2008 Aug 23;372(9639):646-55 - PubMed
  19. J Acquir Immune Defic Syndr. 2015 Aug 1;69(4):439-45 - PubMed
  20. J Clin Pharmacol. 2014 Aug;54(8):949-57 - PubMed
  21. HIV Clin Trials. 2008 Jul-Aug;9(4):213-24 - PubMed
  22. Lancet. 2015 Jun 27;385(9987):2606-15 - PubMed
  23. Antivir Ther. 2011;16(3):339-48 - PubMed
  24. ACS Med Chem Lett. 2010 May 17;1(5):209-13 - PubMed
  25. AIDS. 2011 Apr 24;25(7):929-39 - PubMed
  26. Pharmacotherapy. 2013 Oct;33(10):1107-16 - PubMed
  27. Drugs. 2014 Feb;74(2):195-206 - PubMed
  28. AIDS Res Ther. 2008 Mar 28;5:5 - PubMed
  29. Antivir Ther. 2014;19(6):597-606 - PubMed
  30. Antimicrob Agents Chemother. 2013 Oct;57(10):4982-9 - PubMed
  31. AIDS. 2008 Jul 31;22(12):1389-97 - PubMed
  32. AIDS. 2009 Aug 24;23(13):1679-88 - PubMed
  33. J Intern Med. 2010 Dec;268(6):530-9 - PubMed
  34. J Clin Pharmacol. 2012 Aug;52(8):1128-33 - PubMed
  35. Antivir Ther. 2015;20(5):493-500 - PubMed
  36. J Infect Dis. 2013 Jul;208(1):32-9 - PubMed
  37. J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):310-3 - PubMed
  38. Antimicrob Agents Chemother. 2012 Oct;56(10):5409-13 - PubMed
  39. J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19772 - PubMed
  40. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):401-10 - PubMed
  41. AIDS. 2011 Sep 24;25(15):1881-6 - PubMed
  42. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):483-6 - PubMed
  43. Drugs. 2008;68(5):567-78 - PubMed
  44. Clin Pharmacol Ther. 2010 Mar;87(3):322-9 - PubMed
  45. J Acquir Immune Defic Syndr. 2012 Sep 1;61(1):32-40 - PubMed
  46. Antivir Ther. 2014;19(7):687-92 - PubMed
  47. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8 - PubMed
  48. Pharmacogenet Genomics. 2014 Apr;24(4):195-203 - PubMed
  49. Eur J Pharm Biopharm. 2002 Sep;54(2):107-17 - PubMed
  50. AIDS Res Ther. 2014 Dec 01;11:39 - PubMed
  51. Drug Metab Dispos. 2014 Jan;42(1):9-22 - PubMed
  52. Ann Intern Med. 2011 Apr 5;154(7):445-56 - PubMed

Publication Types