Pharmacological enhancement of protease inhibitors with ritonavir: An update

Expert Review of Clinical Pharmacology

Volumn 1, Issue 4, 2008, Pages 533-545

  Busse, Kristin H ^a   Penzak, Scott R ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Boosting; HIV therapy; Pharmacoenhancement; Protease inhibitor; Ritonavir

Indexed keywords

ABACAVIR; AMPRENAVIR; AMPRENAVIR PHOSPHATE; ANTIRETROVIRUS AGENT; ATAZANAVIR; CYTOCHROME P450 3A4; DARUNAVIR; ENFUVIRTIDE; ESOMEPRAZOLE; FAMOTIDINE; HISTAMINE H2 RECEPTOR ANTAGONIST; INDINAVIR; LAMIVUDINE; LANSOPRAZOLE; LOPINAVIR; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; OMEPRAZOLE; PROTEINASE INHIBITOR; PROTON PUMP INHIBITOR; RALTEGRAVIR; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; TENOFOVIR; TIPRANAVIR; UNINDEXED DRUG; ZIDOVUDINE;

ANTIVIRAL RESISTANCE; BODY FAT DISTRIBUTION; BRAIN HEMORRHAGE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG APPROVAL; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG ERUPTION; DRUG EXPOSURE; DRUG FATALITY; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG WITHDRAWAL; DYSLIPIDEMIA; FOOD DRUG INTERACTION; GASTROINTESTINAL SYMPTOM; HEPATITIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERBILIRUBINEMIA; HYPERGLYCEMIA; HYPERLIPIDEMIA; JAUNDICE; LIPID DIET; LIVER DYSFUNCTION; LIVER TOXICITY; LOW DRUG DOSE; MONOTHERAPY; NEPHROLITHIASIS; PATIENT COMPLIANCE; REPEATED DRUG DOSE; REVIEW; SCLERA DISEASE; SIDE EFFECT; SINGLE DRUG DOSE;

EID: 49549104496     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/17512433.1.4.533     Document Type: Review

References (78)

1. Hammer SM, Katzenstein DA, Hughes MD et al. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. N. Engl. J. Med. 335, 1081-1090 (1996).
2. Saravolatz LD, Winslow DL, Collins G et al. Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter. N. Engl. J. Med. 335, 1099-1106 (1996).
3. Hirsch M, Steigbigel R, Staszewski S et al. A randomized controlled trial of indinavir, zidovudine, and lamivadine in adults with advanced human immunodeficiency vinis type 1 infection and prior zidovudine therapy. J. Infect. Dis. 180, 659-665 (1999).
4. Egger M, Hirschel B, Francioli P et al. Impact of new antiretroviral combination therapies in HIV infected patients in Switzerland: prospective multicentre study. BMJ 315, 1194-1199 (1997).
5. Acosta EP, Kakuda TN, Burndage RC et al. Pharmacodynamics of HIV-1 protease inhibitors. Clin. Infect. Dis. 30, S151-S159 (2000).
6. Durant J, Clevenbergh P, Garraffo R et al. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the VIRADAPT study. AIDS 14, 1333-1339 (2000).
7. Sulkowski MS. Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors. Clin. Infect. Dis. 38, S90-S97 (2004).
8. Norvir®, product information. North Chicago, IL, USA. May 2007.
9. Flexner C. Dual protease inhibitor therapy: pharmacologic rationale and clinical benefits. Annu. Rev. Pharmacol. Toxicol. 40, 649-674 (2000).
10. Yu K, Daar E. Dual proteasc inhibitor therapy. Exp. Opin. Pharmacother. 1, 1331-1342 (2000).
11. Rathbun RC, Rossi DR. Low-dose ritonavir for PI PK enhancement. Ann. Pharmacother. 36, 702-706 (2002).
12. King J, Wynn H, Brundage R, Acosta E. Pharmacokinetic enhancement of protease inhibitor therapy. Clin. Pharmacokinet. 43, 291-310 (2004).
13. Zeldin RK, Petruschke RA. Pharmacological and therapeutic properties. J. Antimicrob. Chemo. 53, 4-9 (2004).
14. Scott JD. Simplifying the treatment of HIV infection. Am. J. Health-Syst. Pharm. 62, 809-815 (2005).
15. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic and pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin. Pharmacokinet. 38, 41-57 (2000).
16. Ernest CS 2nd, Hall SD, Jones DR. Mechanism based inactivation of CYP3A by HIV protease inhibitors. J. Pharmacol. Exp. Ther. 312, 583-591 (2005).
17. Hugen P, Burger DM, ter Hofstede HJM et al. Dose-finding study of a once-daily indinavir/ritonavir regimen. J. Acquir. Immune Defic. Syndr. 25, 236-245 (2000).
18. Molla A, Granneman GR, Sun E et al. Recent developments in HIV protease inhibitor therapy. Anativiral Res. 39, 1-23 (1998).
19. Eagling VA, Back DJ, Barry MG. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir, and indinavir. Br. J. Clin. Pharmacol. 44, 190-194 (1997).
20. Koudriakova T, Latsimirskaia E, Utkin I et al. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab. Dispos. 26, 552-561 (1998).
21. Barry M, Gibbons S, Back D et al. Protease inhibitors in patients with HIV disease. clinically important pharmacokinetic considerations. Clin. Pharmacokinet. 32, 194-209 (1997).
22. Gatmaitan ZC, Arias IM. Structure and function of P-glycoprotein in normal liver and small intestine. Adv. Pharmacol. 24, 77-97 (1993).
23. Viracept®, product information. La Jolla, CA, USA, July 2007.
24. Gallant JE. Protease-inhibitor boosting in the treatment-experienced patient. AIDS Rev. 6, 226-233 (2004).
25. Hsu A, Granneman GR, Cao G et al. Pharmacokinetic interaction between ritonavir and indinavir in healthy volunteers. Antimicrob. Agents Chemother. 42, 2784-2791 (1998).
26. Avihingsanon A, Avihingsanon Y, Darnpornprasert P et al. High prevalence of indinavir-associated renal complications in Thai HIV-infected patients. J. Med. Assoc. Thai. 89(Suppl. 2), S21-S27 (2006).
27. Arnaiz JA, Mallolas J, Pdzamczer D et al. Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load. AIDS 17, 831-840 (2003).
28. Youle M. Overview of boosted protease inhibitors in treatment-experienced HIV-infected patients. J. Antimicrob. Chemother. 60, 1195-1205 (2007).
29. Hammer SM, Saag MS, Schechter M et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society - USA panel. JAMA 296, 827-843 (2006).
30. Kaletra®, product information. North Chicago, IL, USA, November 2007.
31. Klein CE, Chiu YL, Awni W et al. The tablet formulation of lopinavir/ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J. Acquir. Immune Defic. Syndr. 44, 401-410 (2007).
32. Ledergerber B, Egger M, Opravil M et al. Clinical progression and virological fiilure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet 353, 863-868 (1999).
33. Fatkenheuer G, Theisen A, Rockstroh J et al. Virological treatment failure of protease inhibitor therapy in in unselected cohort of HIV-infected patients. AIDS 11, F113-F116 (1997).
34. Wit FW, van Leeuwen R, Weverling GJ et al. Outcome and predictors of failure of highly active antiretroviral therapy: one-year follow-up of a cohort of human immunodeficiency virus type 1-infected persons. J. Infect. Dis. 179, 790-798 (1999).
35. Walmsley S, Bernstein B, King M et al. Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection. N. Engl. J. Med. 346, 2039-2046 (2002).
36. Kempf DJ, King MS, Bernstein B et al. Incidence of resistance in a double-blind study comparing lopinavir/ritonavir plus stavudine and lamivadine to nelfinavir plus staduvdine and lamivudine. J. Infect. Dis. 189, 51-60 (2004).
37. Landay A, da Silva BA, King MS et al. Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir/ritonavir treatment. Clin. Infect. Dis. 44, 749-754 (2007).
38. Johnson MA, Gathe JC Jr, Podzmczer D et al. A once-daily lopinavir/ritonavir-based regimen provides noninferior antiviral activity compared with a twice-daily regimen. J. Acquir. Immune Defic. Syndr. 43, 153-160 (2006).
39. Dube MP, Stein JH, Aberg JA et al. Guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Diseases Society of America and the Adult AIDS Clinical Trial Group. Clin. Infect. Dis. 37, 613-627 (2003).
40. Penzak SR, Chuck SK. Management of protease inhibitor-associated hyperlipidemia. Am. J. Cardiovasc. Drugs 2, 91-106 (2002).
41. Sax PE. Strategies for management and treatment of dyslipidemia in HIV/ AIDS. AIDS Care 18, 149-157 (2006).
42. Reyataz®, product information. Princeton, NJ, USA, March 2008.
43. Amano M, Koh Y, Das D et al. A novel bistetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro. Antimicrob. Agents Chemother. 51, 2143-2155 (2007).
44. Johnson VA, Brun-Vezinet F, Clotet B et al. Update of the drug resistance mutations in HIV-1: Fall 2006. Top. HIV Med. 14, 125-130 (2006).
45. Malan N, Krantz E, David N et al. Efficacy and safety of atazanavir, with or without ritonavir, as a part of once-daily highly active antiretroviral therapy regimens in antiretroviral naïve patients. J. Acquir. Immune Defic. Syndr. 47, 161-167 (2008).
46. Johnson M, Grinsztejn B, Rodriguez C et al. 96-week comparison of once-daily atazanavir/ritonavir and twice daily lopinavir/ritonavir in patients with multiple virologic failures. AIDS 20, 711-718 (2006).
47. Cohen C, Nieto-Cisneros L, Zala C et al. Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial. Curr. Med. Res. Opin. 21, 1683-1692 (2005).
48. Rotger M, Taffe P, Bleiber G et al. Gilbert syndrome and development of antiretroviral therapy associated hyperbilirubinemia. J. Infect. Dis. 192, 1381-1386 (2005).
49. Orrick J, Steinhart C. Atazanavir. Ann. Pharmacother. 38, i664-1674 (2004).
50. Chan-Tack KM, Truff MM, Struble KA, Birnkrant DB. Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration's Adverse Event Reporting System. AIDS 21, 1215-1218 (2007).
51. Isentress®, product information. Whitehouse Station, NJ, USA, October 2007.
52. Luber AD, Brower R, Kim D, Silverman R, Peloquin CA, Frank I. Steady-state pharmacokinetics of once-daily fosamprenavir/ritonavir and atazanavir/ritonavir alone and in combination with 20 mg omeprazole in healthy volunteers. HIV Med. 8, 457-464 (2007).
53. Lexiva®, product information. Research Triangle Park, NC, USA. Oct 2007.
54. Falcoz C, Jenkins JM, Bye C et al. Pharmacokinetics of GW433908, a prodrug of amprenavir in healthy male volunteers. J. Clin. Pharmacol. 42, 887-898 (2002).
55. Eron J Jr, Yeni P, Gathe J Jr et al. The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomized non-inferiority trial. Lancet 368, 476-482 (2006).
56. Gathe JC, Ive P, Wood R et al. SOLO: 48-week efficacy and safety comparison of once-daily fosamprenavir/ritonavir versus twice-daily nelfinavir in naive HIV-1-infected patients. AIDS 18, 1529-1537 (2004).
57. MacManus S, Yates PJ, Elston RC, White S, Richards N, Snowden W. GW433908/ritonavir once daily in antiretroviral therapy-naive HIV-infected patients: absence of protease resistance at 48 weeks. AIDS 18, 651-655 (2004).
58. Rodriguez-French A, Boghossian J, Gray GE et al. The NEAT study: a 48-week open-label study to compare the antiviral efficacy and safity of GW433908 versus nelfinavir in antiretroviral therapy-naive HIV-1 infected patients. J. Acquir. Immune Defic. Syndr. 35, 22-32 (2004).
59. Kashuba AD, Tierney C, Downey GF et al. Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS 19, 145-152 (2005).
60. Zhou SF, Xue CC, Yu XQ Li C, Wang G. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther. Drug Monit. 29, 687-710 (2007).
61. Wertheimer B4 Freedberg KA, Walensky RP, Yazdanapah Y, Losina E. Therapeutic drug monitoring in HIV treatment: a literature review. HIV Clin. Trials 7, 59-69 (2006).
62. Justesen US. Therapeutic drug monitoring and HIV antiretroviral therapy. Basic Clin. Pharmacol. Toxicol. 98, 20-31 (2006).
63. Aptivus®, product information. Ridgefield, CT, USA (2007).
64. Chen L, Sabo JP, Philip E et al. Steady-state disposition of the nonpeptictic protease inhibitor tipranavir when coadministered with ritonavir. Antimirrob. Agents Chemother. 2436-2444 (2007).
65. Gathe J, Cooper DA, Farthing C et al. Efficacy of the protease inhibitors tipranavir plus ritonavir in treatment-experienced patients: 24-week analysis from the RESIST-1 trial. Clin. Infect. Dis. 43, 1337-1346 (2006).
66. Cahn P, Villacian J, Lazzarin A et al. Ritonavir-boosted tipranavir demonstrates superior efficacy to ritonavir-boosted protease inhibitors in treatment-experienced HIV-infected patients: 24-week results of the RESIST-2 trial. Clin. Infect. Dis. 43, 1347-1356 (2006).
67. Naeger LK, Struble KA. Food and drug administration analysis of tipranavir clinical resistance in HIV-1-infected treatment-experienced patients. AIDS 21, 179-185 (2007).
68. 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. 81, 13845-13851 (2007).
69. Prezista™, product information. Raritan, NJ, USA, October 2006.
70. Sekar V, Kestens D, Spinosa-Guzman S et al. The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ ritonavir in HIV-negative healthy volunteers. J. Clin. Pharmacol. 47, 479-484 (2007).
71. Clotet B, Bellos N, Molina JM et al. Efficacy and safety of darunavir-ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: a pooled subgroup analysis of data from two randomized trials. Lancet 369, 1169-1178 (2007).
72. Molina JM, Cohen C, Katlama C. Safety and efficacy or darunavir (TMC114) with low-dose ritonavir in treatment-experienced patients: 24-week results of POWER 3. J. Acquir. Immune Defic. Syndr. 46(1), 24-31 (2007).
73. Hill A, Moyle G. Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials. HIV Med. 8, 259-264 (2007).
74. Madruga JV, Berger D, McMurchie M et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomized controlled Phase III trial. Lancet 370, 49-58 (2007).
75. DeJesus E, Oritz R, Khanlou H et al. Efficacy and safety of darunavir/ritonavir vs. lopinavir/ritonavir in antiretroviral treatment-naive HIV-1-infected patients at week 48: ARTEMIS. Presented at: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA, 17-20 September 2007 (Abstract H-718b).
76. Tennenberg A. Dear Healthcare Professional Letter. In: Important Drug Warning. Tibotec Therapeutics, March (2008).
77. Hogeland GW, Swindells S, McNabb JC et al. Lopinavir/ritonavir reduces bupropion plasma concentrations in healthy subjects. Clin. Pharmacol. Ther. 81, 69-75 (2007).
78. Bertz R, Foit C, Chiu Y-L et al. Multiple-dose Kaletra (lopinavir/ ritonavir) does not affect the pharmacokinetics of the CYP2D6 probe, desipramine. Presented at: 9th Conference on Retraviruses and Opportunistic Infections. Seattle, VA, USA, 24-28 February 2002 (Abstract #433-W).