Rationale and clinical utility of the darunavir–cobicistat combination in the treatment of HIV/AIDS

Drug Design, Development and Therapy

Volumn 9, Issue , 2015, Pages 5763-5769

  Putcharoen, Opass ^a   Do, Tanya ^b   Avihingsanon, Anchalee ^b   Ruxrungtham, Kiat ^a,b  

^a CHULALONGKORN UNIVERSITY   (Thailand)

^b THAI RED CROSS AIDS RESEARCH CENTRE   (Thailand)

Author keywords

Adverse events; Drug drug interactions; First line regime; Pharmacoenhancer; Ritonavir; Tolerability

Indexed keywords

ANTIINFECTIVE AGENT; COBICISTAT; COBICISTAT PLUS DARUNAVIR; COBICISTAT PLUS DARUNAVIR EMTRICITABINE PLUS TENOFOVIR ALAFENAMIDE; COBICISTAT PLUS ELVITEGRAVIR PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; CREATININE; DARUNAVIR; DARUNAVIR PLUS RITONAVIR; EMTRICITABINE; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE; PLACEBO; RITONAVIR; TENOFOVIR ALAFENAMIDE; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; CYTOCHROME P450 3A INHIBITOR; DRUG COMBINATION; HUMAN IMMUNODEFICIENCY VIRUS PROTEINASE INHIBITOR;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AREA UNDER THE CURVE; ARTICLE; COMORBIDITY; CREATININE BLOOD LEVEL; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INTERACTION; DRUG SAFETY; DRUG SOLUBILITY; DRUG TOLERABILITY; DYSLIPIDEMIA; ENZYME MECHANISM; GASTROINTESTINAL SYMPTOM; GLOMERULUS FILTRATION RATE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERBILIRUBINEMIA; JAUNDICE; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS (TOPIC); PATIENT EDUCATION; PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL (TOPIC); TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT WITHDRAWAL; UNSPECIFIED SIDE EFFECT; DRUG COMBINATION; FOOD DRUG INTERACTION; HIV INFECTIONS; RISK FACTOR; TREATMENT OUTCOME; VIROLOGY;

COBICISTAT; CYTOCHROME P-450 CYP3A INHIBITORS; DARUNAVIR; DRUG COMBINATIONS; DRUG INTERACTIONS; FOOD-DRUG INTERACTIONS; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; RISK FACTORS; TREATMENT OUTCOME;

EID: 84945909920     PISSN: None     EISSN: 11778881     Source Type: Journal    
DOI: 10.2147/DDDT.S63989     Document Type: Article

References (42)

1. Hirsch MS, Kuritzkes DR. The future of HIV treatment. J Acquir Immune Defic Syndr. 2012;60(suppl 2):S39–S40.
2. 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. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed April 12, 2015.
3. Este JA, Cihlar T. Current status and challenges of antiretroviral research and therapy. Antiviral Res. 2010;85(1):25–33.
4. Boone LR, Koszalka GW. Antiretroviral drug development for HIV: challenges for the future. Curr Opin Investig Drugs. 2010;11(8):863–867.
5. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141–155.
6. Vitoria M, Vella S, Ford N. Scaling up antiretroviral therapy in resource-limited settings: adapting guidance to meet the challenges. Curr Opin HIV AIDS. 2013;8(1):12–18.
7. Wainberg MA, Zaharatos GJ, Brenner BG. Development of antiretroviral drug resistance. N Engl J Med. 2011;365(7):637–646.
8. Deeks ED. Cobicistat: a review of its use as a pharmacokinetic enhancer of atazanavir and darunavir in patients with HIV-1 infection. Drugs. 2014;74(2):195–206.
9. Xu L, Liu H, Murray BP, et al. Cobicistat (GS-9350): a potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer. ACS medicinal chemistry letters. 2010;1(5):209–213.
10. DeJesus E, Rockstroh JK, Henry K, GS-236-0103 Study Team, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012. 379(9835):2429–2438.
11. Mitra A, Wu Y. Challenges and opportunities in achieving bioequivalence for fixed-dose combination products. AAPS J. 2012;14(3):646–655.
12. Pourkavoos N. Unique risks, benefits, and challenges of developing drug–drug combination products in a pharmaceutical industrial setting. Comb Prod Ther. 2012;2:2.
13. Seelmeier S, Schmidt H, Turk V, von der Helm K. Human immunodeficiency virus has an aspartic-type protease that can be inhibited by pepstatin A. Proc Natl Acad Sci USA. 1988;85(18):6612–6616.
14. Babe LM, Rose J, Craik CS. Trans-dominant inhibitory human immunodeficiency virus type 1 protease monomers prevent protease activation and virion maturation. Proc Natl Acad Sci U S A. 1995;92(22):10069–10073.
15. Davies DR. The structure and function of the aspartic proteinases. Annu Rev Biophys Biophys Chem. 1990;19:189–215.
16. Kohl NE, Emini EA, Schleif WA, et al. Active human immunodeficiency virus protease is required for viral infectivity. Proc Natl Acad Sci U S A. 1988;85(13):4686–4690.
17. Miller M, Schneider J, Sathyanarayana BK, et al. Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. Science. 1989;246(4934):1149–1152.
18. Currier JS. Cardiovascular risk associated with HIV therapy: review by Judith Currier, MD. J. Acquir. Immune Defic. Syndr. 2002;31:S16–S23.
19. Cahn P, Sued O. Boosting HIV treatment options: good news, new challenges. J Infect Dis. 2013;208(1):4–6.
20. King NM, Prabu-Jeyabalan M, Nalivaika EA, Wigerinck P, de Bethune MP, Schiffer CA. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol. 2004;78(21):12012–12021.
21. Dierynck I, De Wit M, Gustin E, et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007;81(24):13845–13851.
22. Ortiz R, Dejesus E, Khanlou H, et al. Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48. AIDS. 2008;22(12):1389–1397.
23. Orkin C, DeJesus E, Khanlou H, et al. Final 192-week efficacy and safety of once-daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV-1-infected treatment-naive patients in the ARTEMIS trial. HIV Med. 2013;14(1):49–59.
24. Deeks ED. Darunavir: a review of its use in the management of HIV-1 infection. Drugs. 2014;74(1):99–125.
25. Zhou S, Yung Chan S, Cher Goh B, et al. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005;44(3):279–304.
26. Kempf DJ, Marsh KC, Kumar G, et al. Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir. Antimicrob Agents Chemother. 1997;41(3):654–660.
27. Hull MW, Montaner JS. Ritonavir-boosted protease inhibitors in HIV therapy. Ann Med. 2011;43(5):375–388.
28. Boffito M, Jackson A, Amara A, et al. Pharmacokinetics of once-daily darunavir-ritonavir and ata zanavir-ritonavir over 72 hours following drug cessation. Antimicrob Agents Chemother. 2011;55(9): 4218–4223.
29. Macías J, Recio E, Márquez M, et al. Efficacy and safety of once-daily maraviroc plus ritonavir-boosted darunavir in pretreated HIV-infected patients in a real-life setting. HIV Med. 2014;15(7):417–424.
30. Mathias AA, German P, Murray BP, et al. Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin Pharmacol Ther. 2010;87(3):322–329.
31. Elion R, Cohen C, Gathe J, et al. Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection. AIDS. 2011;25(15):1881–1886.
32. Gallant JE, Koenig E, Andrade-Villanueva J, et al. Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results. J Infect Dis. 2013;208(1):32–39.
33. Therapeutics J. PREZCOBIX™ (darunavir and cobicistat) [prescribing information]; Janssen Therapeutics, Titusville NJ, USA. 2015.
34. Boffito M, Miralles D, Hill A. Pharmacokinetics, efficacy, and safety of darunavir/ritonavir 800/100 mg once-daily in treatment-naive and -experienced patients. HIV Clin Trials. 2008;9(6):418–427.
35. German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr. 2012;61(1):32–40.
36. Kakuda TN, Van De Casteele T, Petrovic R, et al. Bioequivalence of a darunavir/cobicistat fixed-dose combination tablet versus single agents and food effect in healthy volunteers. Antivir Ther. 2014;19(6):597–606.
37. McDonald CK, Martorell C, Ramgopal M, et al. Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to moderate renal impairment. HIV Clin Trials. 2014;15(6):269–273.
38. Fisher M, McDonald C, Moyle G, et al. Switching from ritonavir to cobicistat in HIV patients with renal impairment who are virologically suppressed on a protease inhibitor. J Int AIDS Soc. 2014;17(4 suppl 3):19824.
39. Tashima K, Crofoot G, Tomaka FL, et al. Cobicistat-boosted darunavir in HIV-1-infected adults: week 48 results of a phase IIIb, open-label single-arm trial. AIDS Res Ther. 2014;11:39.
40. Kakuda TN, Opsomer M, Timmers M, et al. Pharmacokinetics of darunavir in fixed-dose combination with cobicistat compared with coadministration of darunavir and ritonavir as single agents in healthy volunteers. J Clin Pharmacol. 2014;54(8):949–957.
41. Mills A, Crofoot G Jr, McDonald C, et al. Tenofovir alafenamide vs tenofovir disoproxil fumarate in the first protease inhibitor-based single tablet regimen for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2015;69(4):439–445.
42. Medicines Patent Pool Signs Licence Agreement with Gilead to Increase Access to HIV/AIDS Medicines. Available at http://www.medicinespatentpool.org/. Accessed May 27, 2015.