Skip to main content
SpringerLink
Log in

Antiretroviral Therapy

Pharmacokinetic Considerations in Patients with Renal or Hepatic Impairment

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Hepatic and renal insufficiency due to co-infection, alcoholism, diabetes mellitus, family history, adverse effects of antiretrovirals and other factors are commonly seen in HIV-infected patients. Therefore, the use of antiretrovirals in this patient setting requires attention to the pharmacokinetic issues that clinicians must consider when prescribing highly active antiretroviral therapy for these patients. This review summarizes the current knowledge of the use of antiretrovirals in patients with hepatic or renal impairment, and makes dosing recommendations for this subpopulation of HIV-infected patients.

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
Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Thomas DL. Growing importance of liver disease in HIV-infected persons. Hepatology 2006 Feb; 43 (2 Suppl. 1): S221–9

    Article  PubMed  Google Scholar 

  2. Carr A, Cooper DA. Restoration of immunity to chronic hepatitis B infection in HIV-infected patient on protease inhibitor. Lancet 1997; 349(9057): 995–6

    Article  PubMed  CAS  Google Scholar 

  3. Barreiro P, Martin-Carbonero L, Maida I, et al. Liver fibrosis in HIV-infected patients without chronic viral hepatitis: prevalence, clinical characteristics and potential causes [abstract/poster no. 821]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

    Google Scholar 

  4. Fine DM. Renal disease and toxicities: issues for HIV care providers. Top HIV Med 2006 Dec–2007 Jan; 14(5): 164–9

    PubMed  Google Scholar 

  5. Maponga CC, Ma Q, Slish JC, et al. HIV pharmacotherapy issues, challenges, and priorities in sub-Saharan African countries. Top HIV Med 2007 Jun–Jul; 15(3): 104–10

    PubMed  Google Scholar 

  6. Katz I. Kidney and kidney related chronic diseases in South Africa and chronic disease intervention program experiences. Adv Chronic Kidney Dis 2005 Jan; 12(1): 14–21

    Article  PubMed  Google Scholar 

  7. Back DJ, Burger DM, Flexner CW, et al. The pharmacology of antiretroviral nucleoside and nucleotide reverse transcriptase inhibitors: implications for once-daily dosing. J Acquir Immune Defic Syndr 2005 Aug 1; 39 Suppl. 1: S1–23, quiz S24–5

    Article  PubMed  CAS  Google Scholar 

  8. Piliero PJ. Pharmacokinetic properties of nucleoside/nucleotide reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2004 Sep 1; 37 Suppl. 1: S2–S12

    Article  PubMed  CAS  Google Scholar 

  9. Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents [online]. Rockville (MD): Department of Health and Human Services, 2006 Oct 10. Available from URL: http://aidsinfo.nih.gov/Guidelines/Guide-lineDetail.aspx?.MenuItem=Guidelines&Search=Off&Guide-lineID=7&ClassID=1 [Accessed 2008 Jan 10]

  10. Duggan JM, Sahloff EG, Moudgal VV. Use of highly active antiretroviral therapy in patients with renal insufficiency. Pharmacotherapy 2005 May; 25(5): 698–708

    Article  PubMed  CAS  Google Scholar 

  11. Izzedine H, Launay-Vacher V, Baumelou A, et al. An appraisal of antiretroviral drugs in hemodialysis. Kidney Int 2001 Sep; 60(3): 821–30

    Article  PubMed  CAS  Google Scholar 

  12. Wyles DL, Gerber JG. Antiretroviral drug pharmacokinetics in hepatitis with hepatic dysfunction. Clin Infect Dis 2005 Jan 1; 40(1): 174–81

    Article  PubMed  CAS  Google Scholar 

  13. European Medicines Agency. EPARs for authorised medicinal products for human use: Ziagen [product information; online]. Available from: http://www.emea.europa.eu/humandocs/Humans/EPAR/ziagen/ziagen.htm [Accessed 2007 Dec 19]

  14. Izzedine H, Launay-Vacher V, Aymard G, et al. Pharmacokinetics of abacavir in HIV-1-infected patients with impaired renal function. Nephron 2001 Sep; 89(1): 62–7

    Article  PubMed  CAS  Google Scholar 

  15. Singlas E, Taburet AM, Borsa Lebas F, et al. Didanosine pharmacokinetics in patients with normal and impaired renal function: influence of hemodialysis. Antimicrob Agents Chemother 1992 Jul; 36(7): 1519–24

    Article  PubMed  CAS  Google Scholar 

  16. Knupp CA, Hak LJ, Coakley DF, et al. Disposition of didanosine in HIV-seropositive patients with normal renal function or chronic renal failure: influence of hemodialysis and continuous ambulatory peritoneal dialysis. Clin Pharmacol Ther 1996 Nov; 60(5): 535–42

    Article  PubMed  CAS  Google Scholar 

  17. Emtriva® [prescribing information; online]. Foster City (CA): Gilead Sciences, Inc. 2006. Available from URL: http://www.gilead.com/pdf/emtriva_pi.pdf [Accessed 2007 Dec 19]

  18. Frampton JE, Perry CM. Emtricitabine: a review of its use in the management of HIV infection. Drugs 2005; 65(10): 1427–48

    Article  PubMed  CAS  Google Scholar 

  19. van Leeuwen R, Lange JM, Hussey EK, et al. The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study. AIDS 1992 Dec; 6(12): 1471–5

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  21. Bohjanen PR, Johnson MD, Szczech LA, et al. Steady-state pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with end-stage renal disease receiving chronic dialysis. Antimicrob Agents Chemother 2002 Aug; 46(8): 2387–92

    Article  PubMed  CAS  Google Scholar 

  22. Rana KZ, Dudley MN. Clinical pharmacokinetics of stavudine. Clin Pharmacokinet 1997 Oct; 33(4): 276–84

    Article  PubMed  CAS  Google Scholar 

  23. Schaad HJ, Petty BG, Grasela DM, et al. Pharmacokinetics and safety of a single dose of stavudine (d4T) in patients with severe hepatic impairment. Antimicrob Agents Chemother 1997 Dec; 41(12): 2793–6

    PubMed  CAS  Google Scholar 

  24. Grasela DM, Stoltz RR, Barry M, et al. Pharmacokinetics of single-dose oral stavudine in subjects with renal impairment and in subjects requiring hemodialysis. Antimicrob Agents Chemother 2000 Aug; 44(8): 2149–53

    Article  PubMed  CAS  Google Scholar 

  25. Taburet AM, Gerard L, Legrand M, et al. Antiretroviral drug removal by haemodialysis. AIDS 2000 May 5; 14(7): 902–3

    Article  PubMed  CAS  Google Scholar 

  26. Kearney BP, Flaherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin Pharmacokinet 2004; 43(9): 595–612

    Article  PubMed  CAS  Google Scholar 

  27. Heffelfinger J, Hanson D, Voetsch A, et al. Renal impairment associated with the use of tenofovir [abstract/poster no. 779]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

    Google Scholar 

  28. Mauss S, Berger F, Schmutz G. Antiretroviral therapy with tenofovir is associated with mild renal dysfunction. AIDS 2005 Jan 3; 19(1): 93–5

    Article  PubMed  CAS  Google Scholar 

  29. Julg BD, Bogner JR, Crispin A, et al. Progression of renal impairment under therapy with tenofovir. AIDS 2005 Aug 12; 19(12): 1332–3

    Article  PubMed  Google Scholar 

  30. Moore RD, Keruly JC, Gallant JE. Tenofovir and renal dysfunction in clinical practice [abstract no. 832]. 4th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)

    Google Scholar 

  31. Gallant JE, Parish MA, Keruly JC, et al. Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. Clin Infect Dis 2005 Apr 15; 40(8): 1194–8

    Article  PubMed  CAS  Google Scholar 

  32. Staszewski S, Pozniak A, Gallant JE, et al. Renal saftey profile of tenofovir DF (TDF)-containing compared to non-TDF-containing regimens in antiretroviral-naive patients with mild renal impairment or hypertension and/or diabetes mellitus [abstract]. 8th International Congress on Drug Therapy in HIV Infection; 2006 Nov 12–16; Glasgow

    Google Scholar 

  33. Hivid® [product information]. Nutley, UK: Roche, 2003

  34. Bazunga M, Tran HT, Kertland H, et al. The effects of renal impairment on the pharmacokinetics of zalcitabine. J Clin Pharmacol 1998 Jan; 38(1): 28–33

    PubMed  CAS  Google Scholar 

  35. Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005 Jun 1; 40(11): 1559–85

    Article  PubMed  Google Scholar 

  36. Taburet AM, Naveau S, Zorza G, et al. Pharmacokinetics of zidovudine in patients with liver cirrhosis. Clin Pharmacol Ther 1990 Jun; 47(6): 731–9

    Article  PubMed  CAS  Google Scholar 

  37. Moore KH, Raasch RH, Brouwer KL, et al. Pharmacokinetics and bioavailability of zidovudine and its glucuronidated metabolite in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group protocol 062). Antimicrob Agents Chemother 1995 Dec; 39(12): 2732–7

    Article  PubMed  CAS  Google Scholar 

  38. Singlas E, Pioger JC, Taburet AM, et al. Zidovudine disposition in patients with severe renal impairment: influence of hemodialysis. Clin Pharmacol Ther 1989 Aug; 46(2): 190–7

    Article  PubMed  CAS  Google Scholar 

  39. Ma Q, Okusanya OO, Smith PF, et al. Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors. Expert Opin Drug Metab Toxicol 2005 Oct; 1(3): 473–85

    Article  PubMed  CAS  Google Scholar 

  40. Csajka C, Marzolini C, Fattinger K, et al. Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharmacol Ther 2003 Jan; 73(1): 20–30

    Article  PubMed  CAS  Google Scholar 

  41. Ma Q, Okusanya OO, Smith PF, et al. Pharmacokinetic drug interactions with non-nucleoside reverse transcriptase inhibitors. Expert Opin Drug Metab Toxicol 2005 Oct; 1(3): 473–85

    Article  PubMed  CAS  Google Scholar 

  42. Intelence® [prescribing information; online]. Raritan (NJ): Tibotec Therapeutics, 2008. Available from URL: http://www.tibotectherapeutics.com/tibotectherapeutics/documents/TMC125_20080118_USPI_USPPI_v1_0.pdf [Accessed 2008 Feb 1]

  43. Sustiva® [prescribing information; online]. Princeton (NJ): Bristol Myers Squibb Company, 2006. Available from URL: http://packageinserts.bms.com/pi/pi_sustiva.pdf [Accessed 2008 Feb 1]

  44. Angel-Moreno-Maroto A, Suarez-Castellano L, Hernandez-Cabrera M, et al. Severe efavirenz-induced hypersensitivity syndrome (not-DRESS) with acute renal failure. J Infect 2006 Feb; 52(2): e39–40

    Article  PubMed  Google Scholar 

  45. Rivero A, Mira JA, Pineda JA. Liver toxicity induced by non-nucleoside reverse transcriptase inhibitors. J Antimicrob Chemother 2007; 59: 342–6

    Article  PubMed  CAS  Google Scholar 

  46. Kappelhoff BS, van Leth F, Robinson PA, et al. Are adverse events of nevirapine and efavirenz related to plasma concentrations? Antivir Ther 2005; 10(4): 489–98

    PubMed  CAS  Google Scholar 

  47. Barreiro P, Rodriguez-Novoa S, Labarga P, et al. Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C. J Infect Dis 2007 Apr 1; 195(7): 973–9

    Article  PubMed  CAS  Google Scholar 

  48. Viramune® [prescribing information; online]. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc., 2007. Available from URL: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetn&tfolderPath=/Prescribing+Information/PIs/Viramune/Viramune.pdf [Accessed 2008 Feb 1]

  49. Knudtson E, Para M, Boswell H, et al. Drug rash with eosinophilia and systemic symptoms syndrome and renal toxicity with a nevirapine-containing regimen in a pregnant patient with human immunodeficiency virus. Obstet Gynecol 2003 May; 101 (5 Pt 2): 1094–7

    Article  PubMed  Google Scholar 

  50. Rescriptor® [prescribing information; online]. New York: Pfizer, Inc., 2006. Available from URL: http://www.pfizer.com/files/products/uspi_rescriptor.pdf [Accessed 2008 Feb 1]

  51. Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2004 Dec; 48(12): 4680–6

    Article  PubMed  CAS  Google Scholar 

  52. Vingerhoets J, Azijn H, Fransen E, et al. TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol 2005 Oct; 79(20): 12773–82

    Article  PubMed  CAS  Google Scholar 

  53. Nadler JP, Berger DS, Blick G, et al. Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS 2007 Mar 30; 21(6): F1–10

    Article  PubMed  CAS  Google Scholar 

  54. Moyle GJ, Back D. Principles and practice of HIV-protease inhibitor pharmacoen-hancement. HIV Med 2001 Apr; 2(2): 105–13

    Article  PubMed  CAS  Google Scholar 

  55. Crixivan® [prescribing information; online]. Whitehouse Station (NJ): Merck & Co., Inc, 2004 [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/c/crixivan/crixivan_pi.pdf [Accessed 2007 Dec 19]

  56. Reyataz® [prescribing information; online]. Princeton (NJ): Bristol-Myers Squibb, 2006. Available from URL: http://packageinserts.bms.com/pi/pi_reyataz.pdf [Accessed 2007 Dec 19]

  57. Viracept® [prescribing information; online]. La Jolla (CA): Agouron Pharmaceuticals, Inc., 2007. Available from URL: http://www.pfizer.com/files/products/uspi_viracept.pdf [Accessed 2007 Dec 19]

  58. Best B, Haubrich R. Tipranavir: a protease inhibitor for multi-drug resistant HIV-1. Expert Opin Investig Drugs 2006 Jan; 15(1): 59–70

    Article  PubMed  CAS  Google Scholar 

  59. Dong BJ, Cocohoba JM. Tipranavir: a protease inhibitor for HIV salvage therapy. Ann Pharmacother 2006 Jul–Aug; 40(7–8): 1311–21

    PubMed  CAS  Google Scholar 

  60. Shurtleff AC. TMC-114 (Tibotec). Curr Opin Investig Drugs 2004 Aug; 5(8): 879–86

    PubMed  CAS  Google Scholar 

  61. Slish JC, Catanzaro LM, Ma Q, et al. Update on the pharmacokinetic aspects of antiretroviral agents: implications in therapeutic drug monitoring. Curr Pharm Des 2006; 12(9): 1129–45

    Article  PubMed  CAS  Google Scholar 

  62. Invirase® [prescribing information; online]. Nutley (NJ): Roche Laboratories Inc., 2007. Available from URL: http://www.rocheusa.com/products/invirase/pi.pdf [Accessed 2008 Feb 1]

  63. Kaletra® [prescribing information; online]. North Chicago (IL): Abbott Laboratories, 2007. Available from URL: http://www.rxabbott.com/pdf/kaletratabpi.pdf [Accessed 2007 Dec 19]

  64. Cordon-Cardo C, O’Brien JP, Casals D, et al. Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc Natl Acad Sci USA 1989 Jan; 86(2): 695–8

    Article  PubMed  CAS  Google Scholar 

  65. Pileri SA, Sabattini E, Falini B, et al. Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas. Histopathology 1991 Aug; 19(2): 131–40

    Article  PubMed  CAS  Google Scholar 

  66. Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987 Nov; 84(21): 7735–8

    Article  PubMed  CAS  Google Scholar 

  67. Fellay J, Marzolini C, Meaden ER, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet 2002 Jan 5; 359(9300): 30–6

    Article  PubMed  CAS  Google Scholar 

  68. Agenerase® [prescribing information; online]. Research Triangle Park (NC): GlaxoSmithKline, 2005. Available from URL: http://www.gsk.com/products/prescription_medicines/us/agenerase_us.htm [Accessed 2007 Dec 19]

  69. Okusanya O, Forrest A, DiFrancesco R, et al. Compartmental pharmacokinetic analysis of oral amprenavir with secondary peaks. Antimicrob Agents Chemother 2007 May; 51(5): 1822–6

    Article  PubMed  CAS  Google Scholar 

  70. Veronese L, Rautaureau J, Sadler BM, et al. Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function. Antimicrob Agents Chemother 2000 Apr; 44(4): 821–6

    Article  PubMed  CAS  Google Scholar 

  71. Breilh D, Guinguene S, de Ledinghen V, et al. Pharmacokinetics of boosted protease inhibitors and non nucleoside reverse transcriptase inhibitors in HCV-HIV co-infected patients [abstract no. 946; online]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA). Available from URL: http://www.retroconference.org/2007/PDFs/946.pdf [Accessed 2008 Feb 5]

    Google Scholar 

  72. Brewster U, Perazella M. Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. Am J Kidney Dis 2004; 44(5): e81–4

    PubMed  Google Scholar 

  73. Chang HR, Pella PM. Atazanavir urolithiasis. N Engl J Med 2006 Nov 16; 355(20): 2158–9

    Article  PubMed  CAS  Google Scholar 

  74. Pacanowski J, Poirier JM, Petit I, et al. Atazanavir urinary stones in an HIV-infected patient. AIDS 2006 Oct 24; 20(16): 2131

    Article  PubMed  Google Scholar 

  75. Chan-Tack KM, Truffa MM, Struble KA, et al. Atazanavir-associated nephrolithiasis: cases from the US Food and Drug Administration’s Adverse Event Reporting System. AIDS 2007 May 31; 21(9): 1215–8

    Article  PubMed  CAS  Google Scholar 

  76. Gentle DL, Stoller ML, Jarrett TW, et al. Protease inhibitor-induced urolithiasis. Urology 1997 Oct; 50(4): 508–11

    Article  PubMed  CAS  Google Scholar 

  77. Dieleman JP, Gyssens IC, van der Ende ME, et al. Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients. AIDS 1999 Mar 11; 13(4): 473–8

    Article  PubMed  CAS  Google Scholar 

  78. Bossi P, Peytavin G, Lamotte C, et al. High indinavir plasma concentrations in HIV-positive patients co-infected with hepatitis B or C virus treated with low doses of indinavir and ritonavir (400/100 mg twice a day) plus two nucleoside reverse transcriptase inhibitors. AIDS 2003 May 2; 17(7): 1108–10

    Article  PubMed  Google Scholar 

  79. Peng JZ, Pulido F, Causemaker SJ, et al. Pharmacokinetics of lopinavir/ritonavir in HIV/hepatitis C virus-coinfected subjects with hepatic impairment. J Clin Pharmacol 2006 Mar; 46(3): 265–74

    Article  PubMed  CAS  Google Scholar 

  80. Molt′ J, Valle M, Blanco A, et al. Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis. Clin Pharmacokinet 2007; 46(1): 85–92

    Article  Google Scholar 

  81. Damle B, Hewlett Jr D, Hsyu PH, et al. Pharmacokinetics of nelfinavir in subjects with hepatic impairment. J Clin Pharmacol 2006 Nov; 46(11): 1241–9

    Article  PubMed  CAS  Google Scholar 

  82. Khaliq Y, Gallicano K, Seguin I, et al. Single and multiple dose pharmacokinetics of nelfinavir and CYP2C19 activity in human immunodeficiency virus infected patients with chronic liver disease. Br J Clin Pharmacol 2000; 50(2): 108–15

    Article  PubMed  CAS  Google Scholar 

  83. Regazzi M, Maserati R, Villani P, et al. Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects. Antimicrob Agents Chemother 2005 Feb; 49(2): 643–9

    Article  PubMed  CAS  Google Scholar 

  84. Tachikawa N, Yoshizawa S, Kikuchi Y, et al. Saquinavir therapy in patients with the advanced HIV infection and liver cirrhosis. Jpn J Infect Dis 1999 Aug; 52(4): 177–8

    PubMed  CAS  Google Scholar 

  85. Aptivus® [prescribing information; online]. Ridgefield (CT): Boehringer Ingelheim Pharmaceuticals, Inc., 2005. Available from URL: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Aptivus/l0003515+US+01.pdf [Accessed 2008 Feb 1]

  86. Cooper C, van Heeswijk R, Bilodeau M, et al. The pharmacokinetics (PK) of single-dose and steady-state tipranavir/ritonavir (TPV/r) 500 mg/200 mg in subjects with mild or moderate hepatic impairment [abstract no. 45]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City

    Google Scholar 

  87. Julg B, Bogner JR, Goebel FD. Severe hepatotoxicity associated with the combination of enfuvirtide and tipranavir/ritonavir: case report. AIDS 2006 Jul 13; 20(11): 1563

    Article  PubMed  Google Scholar 

  88. Fuzeon® (enfuvirtide) for injection [prescribing information; online]. Nutley (NJ): Roche Laboratories Inc., 2007 Jan. Available from URL: http://rocheusa.com/products/fuzeon/pi.pdf [Accessed 2008 Jan 10]

  89. Tebras P, Bellos N, Lucasti C, et al. Enfuvirtide does not require dose-adjustment in patients with chronic renal failure: the results of a pharmacokinetic study of enfuvirtide in HIV-1 infected patients with impaired function [poster no. L-108]. 14th Conference on Retroviruses and Opportunistic Infections (CROI); 2007 Feb 25–28; Los Angeles (CA)

    Google Scholar 

  90. Walker DK, Abel S, Comby P, et al. Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV. Drug Metab Dispos 2005 Apr; 33(4): 587–95

    Article  PubMed  CAS  Google Scholar 

  91. Pfizer Inc. Maraviroc tablets NDA 22–128: Antiviral Drugs Advisory Commitee (AVDAC) briefing document [online]. Rockville (MD): US FDA, 2007 Apr 24. Available from URL: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4283bl-01-Pfizer.pdf [Accessed 2008 Jan 10]

    Google Scholar 

  92. Abel S, Ridgway C, Hamlin J, et al. An open, parallel group study to compare the pharmacokinetics, safety and toleration of a single oral dose of maraviroc in subjects with mild and moderate hepatic impairment with subjects with normal hepatic function [abstract no. 2]. 8th International Workshop on Clinical Pharmacology of HIV Therapy; 2007 Apr 16–18; Budapest

    Google Scholar 

  93. Markowitz M, Nguyen B-Y, Gotuzzo E, et al. Rapid onset and durable antiretroviral effect of raltegravir (MK-0518), a novel HIV-1 integrase inhibitor, as part of combination ART in treatment HIV-1 infected patients: 48-week data [abstract no. TUAB104]. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; Sydney

    Google Scholar 

  94. Bica I, McGovern B, Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001 Feb 1; 32(3): 492–7

    Article  PubMed  CAS  Google Scholar 

  95. Cacoub P, Geffray L, Rosenthal E, et al. Mortality among human immunodeficiency virus-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases, in 1995 and 1997. Clin Infect Dis 2001 Apr 15; 32(8): 1207–14

    Article  PubMed  CAS  Google Scholar 

  96. Martin-Carbonero L, Soriano V, Valencia E, et al. Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses 2001 Nov 1; 17(16): 1467–71

    Article  PubMed  CAS  Google Scholar 

  97. Rosenthal E, Poiree M, Pradier C, et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). AIDS 2003 Aug 15; 17(12): 1803–9

    Article  PubMed  Google Scholar 

  98. Brau N. Chronic hepatitis C in patients with HIV/AIDS: a new challenge in antiviral therapy. J Antimicrob Chemother 2005 Dec; 56(6): 991–5

    Article  PubMed  CAS  Google Scholar 

  99. Saillour F, Dabis F, Dupon M, et al. Prevalence and determinants of antibodies to hepatitis C virus and markers for hepatitis B virus infection in patients with HIV infection in Aquitaine. Groupe d’Epidemiologie Clinique du SIDA en Aquitaine. BMJ 1996 Aug 24; 313(7055): 461–4

    Article  PubMed  CAS  Google Scholar 

  100. El-Serag HB, Giordano TP, Kramer J, et al. Survival in hepatitis C and HIV coinfection: a cohort study of hospitalized veterans. Clin Gastroenterol Hepatol 2005 Feb; 3(2): 175–83

    Article  PubMed  Google Scholar 

  101. Giordano TP, Kramer JR, Souchek J, et al. Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus: a cohort study, 1992–2001. Arch Intern Med 2004 Nov 22; 164(21): 2349–54

    Article  PubMed  Google Scholar 

  102. Kramer JR, Giordano TP, Souchek J, et al. Hepatitis C coinfection increases the risk of fulminant hepatic failure in patients with HIV in the HAART era. J Hepatol 2005 Mar; 42(3): 309–14

    Article  PubMed  Google Scholar 

  103. Greub G, Ledergerber B, Battegay M, et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 2000 Nov 25; 356(9244): 1800–5

    Article  PubMed  CAS  Google Scholar 

  104. Konopnicki D, Mocroft A, de Wit S, et al. Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 2005 Mar 24; 19(6): 593–601

    Article  PubMed  Google Scholar 

  105. Thio CL, Seaberg EC, Skolasky Jr R, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002 Dec 14; 360(9349): 1921–6

    Article  PubMed  Google Scholar 

  106. Mocroft A, Soriano V, Rockstroh J, et al. Is there evidence for an increase in the death rate from liver-related disease in patients with HIV? AIDS 2005 Dec 2; 19(18): 2117–25

    Article  PubMed  Google Scholar 

  107. Mehta SH, Thomas DL, Torbenson M, et al. The effect of antiretroviral therapy on liver disease among adults with HIV and hepatitis C coinfection. Hepatology 2005 Jan; 41(1): 123–31

    Article  PubMed  Google Scholar 

  108. Tural C, Fuster D, Tor J, et al. Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients. J Viral Hepat 2003 Mar; 10(2): 118–25

    Article  PubMed  CAS  Google Scholar 

  109. Weber R, Sabin C, Friis-Moller N, et al. Exposure to antiretroviral therapy and the risk of liver-related death: is there an association? Results from the D:A:D study [abstract no. 770]. 13th Conference of Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)

    Google Scholar 

  110. Saves M, Vandentorren S, Daucourt V, et al. Severe hepatic cytolysis: incidence and risk factors in patients treated by antiretroviral combinations. Aquitaine Cohort, France, 1996–1998. Groupe d’Epidemiologie Clinique de Sida en Aquitaine (GECSA). AIDS 1999 Dec 3; 13(17): F115–21

    Article  PubMed  CAS  Google Scholar 

  111. Sulkowski MS, Thomas DL, Chaisson RE, et al. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000 Jan 5; 283(1): 74–80

    Article  PubMed  CAS  Google Scholar 

  112. den Brinker M, Wit FW, Wertheim-van Dillen PM, et al. Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection. AIDS 2000 Dec 22; 14(18): 2895–902

    Article  Google Scholar 

  113. Mauss S, Stern J, Elgadi M, et al. RESIST 24-week efficacy and safety of tipranavir boosted with ritonavir (TPR/r) in hepatitis B (HBV) or hepatitis C (HCV) co infected patient [poster no. PE13.3.4]. 10th European AIDS Conference; 2005 Nov 17–20; Dublin

    Google Scholar 

  114. Rockstroh J, Sulkowski M, Neubacher D, et al. 24-week efficacy of tipranavir boosted with ritonavir (TPV/r) in hepatitis B (HBV) or hepatitis C (HCV) co-infected patients [abstract no. H-525] 45th Annual Interscience Conference of Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington (DC)

    Google Scholar 

  115. Dicenzo R, Luque A, Larppanichpoonphol P, et al. Association of total bilirubin with indinavir and lopinavir plasma concentrations in HIV-infected patients receiving three different double-boosted dosing regimens. J Antimicrob Chemother 2006 Aug; 58(2): 393–400

    Article  PubMed  CAS  Google Scholar 

  116. Seminari E, Gentilini G, Galli L, et al. Higher plasma lopinavir concentrations are associated with a moderate rise in cholestasis markers in HIV-infected patients. J Antimicrob Chemother 2005 Oct; 56(4): 790–2

    Article  PubMed  CAS  Google Scholar 

  117. Quirk E, McLeod H, Powderly W. The pharmacogenetics of antiretroviral therapy: a review of studies to date. Clin Infect Dis 2004 Jul 1; 39(1): 98–106

    Article  PubMed  CAS  Google Scholar 

  118. Zucker SD, Qin X, Rouster SD, et al. Mechanism of indinavir-induced hyperbilirubinemia. Proc Natl Acad Sci U S A 2001 Oct 23; 98(22): 12671–6

    Article  PubMed  CAS  Google Scholar 

  119. Rayner CR, Esch LD, Wynn HE, et al. Symptomatic hyperbilirubinemia with indinavir/ritonavir-containing regimen. Ann Pharmacother 2001 Nov; 35(11): 1391–5

    Article  PubMed  CAS  Google Scholar 

  120. Verdon R, Daudon M, Albessard F, et al. Indinavir-induced cholelithiasis in a patient infected with human immunodeficiency virus. Clin Infect Dis 2002 Sep 1; 35(5): e57–9

    Article  PubMed  Google Scholar 

  121. Sanne I, Piliero P, Squires K, et al. Results of a phase 2 clinical trial at 48 weeks (AI424-007): a dose-ranging, safety, and efficacy comparative trial of atazanavir at three doses in combination with didanosine and stavudine in antiretroviral-naive subjects. J Acquir Immune Defic Syndr 2003 Jan 1; 32(1): 18–29

    Article  PubMed  CAS  Google Scholar 

  122. Rodriguez Novoa S, Barreiro P, Rendon A, et al. Plasma levels of atazanavir and the risk of hyperbilirubinemia are predicted by the 3435C→T polymorphism at the multidrug resistance gene 1. Clin Infect Dis 2006 Jan 15; 42(2): 291–5

    Article  Google Scholar 

  123. Smith DE, Jeganathan S, Ray J. Atazanavir plasma concentrations vary significantly between patients and correlate with increased serum bilirubin concentrations. HIV Clin Trials 2006 Jan–Feb; 7(1): 34–8

    Article  PubMed  Google Scholar 

  124. Canta F, Marrone R, Bonora S, et al. Pharmacokinetics and hepatotoxicity of lopinavir/ritonavir in non-cirrhotic HIV and hepatitis C virus (HCV) co-infected patients [letter]. J Antimicrob Chemother 2005 Feb; 55(2): 280–1

    Article  PubMed  CAS  Google Scholar 

  125. Gonzalez-Requena D, Nunez M, Jimenez-Nacher I, et al. Short communication: liver toxicity of lopinavir-containing regimens in HIV-infected patients with or without hepatitis C coinfection. AIDS Res Hum Retroviruses 2004 Jul; 20(7): 698–700

    Article  PubMed  CAS  Google Scholar 

  126. Solas C, Lafeuillade A, Halfon P, et al. Discrepancies between protease inhibitor concentrations and viral load in reservoirs and sanctuary sites in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2003 Jan; 47(1): 238–43

    Article  PubMed  CAS  Google Scholar 

  127. Livry C, Binquet C, Sgro C, et al. Acute liver enzyme elevations in HIV-1-infected patients. HIV Clin Trials 2003 Nov–Dec; 4(6): 400–10

    Article  PubMed  Google Scholar 

  128. Meraviglia P, Schiavini M, Castagna A, et al. Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation. HIV Med 2004 Sep; 5(5): 334–43

    Article  PubMed  CAS  Google Scholar 

  129. Acosta EP, Gerber JG. Position paper on therapeutic drug monitoring of antiretroviral agents. AIDS Res Hum Retroviruses 2002 Aug 10; 18(12): 825–34

    Article  PubMed  CAS  Google Scholar 

  130. Burger DM, Hugen PW, Aarnoutse RE, et al. Treatment failure of nelfinavircontaining triple therapy can largely be explained by low nelfinavir plasma concentrations. Ther Drug Monit 2003 Feb; 25(1): 73–80

    Article  PubMed  CAS  Google Scholar 

  131. Wertheimer BZ, Freedberg KA, Walensky RP, et al. Therapeutic drug monitoring in HIV treatment: a literature review. HIV Clin Trials 2006 Mar–Apr; 7(2): 59–69

    Article  PubMed  Google Scholar 

  132. Morse GD, Catanzaro LM, Acosta EP. Clinical pharmacodynamics of HIV-1 protease inhibitors: use of inhibitory quotients to optimise pharmacotherapy. Lancet Infect Dis 2006 Apr; 6(4): 215–25

    Article  PubMed  CAS  Google Scholar 

  133. Slish JC, Catanzaro LM, Ma Q, et al. Update on the pharmacokinetic aspects of antiretroviral agents: implications in therapeutic drug monitoring. Curr Pharm Des 2006; 12(9): 1129–45

    Article  PubMed  CAS  Google Scholar 

  134. Flexner C. Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits. Annu Rev Pharmacol Toxicol 2000; 40: 649–74

    Article  PubMed  CAS  Google Scholar 

  135. Anderson PL, Fletcher CV. Clinical pharmacologic considerations for HIV-1 protease inhibitors. Curr Infect Dis Rep 2001 Aug; 3(4): 381–7

    Article  PubMed  Google Scholar 

  136. Murray M. P450 enzymes: inhibition mechanisms, genetic regulation and effects of liver disease. Clin Pharmacokinet 1992 Aug; 23(2): 132–46

    Article  PubMed  CAS  Google Scholar 

  137. Szczech LA, Hoover DR, Feldman JG, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis 2004 Oct 15; 39(8): 1199–206

    Article  PubMed  Google Scholar 

  138. Fine DM. Renal disease and toxicities: issues for HIV care providers. Top HIV Med 2006 Dec; 14(5): 164–9

    PubMed  Google Scholar 

  139. Ross MJ, Klotman PE, Winston JA. HIV-associated nephropathy: case study and review of the literature. AIDS Patient Care STDs 2000 Dec; 14(12): 637–45

    Article  PubMed  CAS  Google Scholar 

  140. Roling J, Schmid H, Fischereder M, et al. HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy. Clin Infect Dis 2006 May 15; 42(10): 1488–95

    Article  PubMed  CAS  Google Scholar 

  141. Gardner LI, Holmberg SD, Williamson JM, et al. HIV epidemiology research study group: development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. J Acquir Immune Defic Syndr 2003 Feb 1; 32(2): 203–9

    Article  PubMed  CAS  Google Scholar 

  142. Szczech LA, Gange SJ, van der Horst C, et al. Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 2002 Jan; 61(1): 195–202

    Article  PubMed  Google Scholar 

  143. Winston JA, Klotman ME, Klotman PE. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection. Kidney Int 1999 Mar; 55(3): 1036–40

    Article  PubMed  CAS  Google Scholar 

  144. Tokars JI, Frank M, Alter MJ, et al. National surveillance of dialysis-associated diseases in the United States, 2000. Semin Dial 2002 May–Jun; 15(3): 162–71

    Article  PubMed  Google Scholar 

  145. Eggers PW, Kimmel PL. Is there an epidemic of HIV-associated nephropathy in the ESRD program? J Am Soc Nephrol 2004 Sep; 15(9): 2477–85

    Article  PubMed  Google Scholar 

  146. US Renal Data System. 2003 annual data report: atlas of end-stage renal disease in the United States. Bethesda (MD): National Institutes of Diabetes and Digestive and Kidney Diseases, 2003

    Google Scholar 

Download references

Acknowledgements

Dr Morse is supported in part by grant #5R01DA015024-02 from the US National Institute on Drug Abuse and grant #5UO1A127658-16 from the US National Institute of Allergy and Infectious Diseases. Dr Dicenzo is supported in part by grant #5UO1A127658-16 from the US National Institute of Allergy and Infectious Diseases. Dr McCabe is a UB-Novartis Drug Development Fellow. Dr Catanzaro has received speaker’s honoraria from Abbott Laboratories, Inc. and Gilead Science, Inc. within the past 5 years. Dr Sheth is an HIV Pharmacotherapy Specialty Resident supported through Ryan White Title I funding. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Department of Pharmacy Practice and Pharmacotherapy Research Center, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA

    Sarah M. McCabe, Qing Ma, Judianne C. Slish, Linda M. Catanzaro, Neha Sheth, Robert DiCenzo & Gene D. Morse

  2. Immunodeficiency Services, Erie County Medical Center, Buffalo, New York, USA

    Judianne C. Slish, Linda M. Catanzaro, Neha Sheth & Gene D. Morse

Authors
  1. Sarah M. McCabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qing Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Judianne C. Slish
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Linda M. Catanzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Neha Sheth
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert DiCenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gene D. Morse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gene D. Morse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McCabe, S.M., Ma, Q., Slish, J.C. et al. Antiretroviral Therapy. Clin Pharmacokinet 47, 153–172 (2008). https://doi.org/10.2165/00003088-200847030-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200847030-00002

Keywords

Search

Navigation