Co-infection with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) is becoming a rampant disparity in HIV-infected patients. The advent of antiretroviral therapy has led to agents that are effective for suppression of both HIV and HBV; however, this can not be extrapolated to patients who are coinfected with HCV. Treatment of HCV disease is often strenuous and can lead to untoward adverse effects. Co-infection with HIV often leads to higher rates of cirrhosis and liver failure in patients with HBV or HCV, compromising antiretroviral treatment in this patient population due to the hepatotoxicity of these agents. The purpose of this review is to familiarize health care providers to the management of HIV infection in patients who are also co-infected with HBV or HCV.
Treatment Action Group. Hepatitis C virus (HCV) and HIV/HCV co-infection. Available at: www.aidsinfonyc.org/tag/coinf/hcv2004/chap1.html. Accessed November 2004.
Alter H, Chung R, Davis G, et al. Clinical care options for hepatitis: annual update 2003. iMed Options2003:65-72.
4.
Thio C. Management of chronic hepatitis B in the HIV-infected patient. AIDS Read. 2004;14:1122-1137.
5.
Bonacini M, Puoti M. Hepatitis C in patients with human immunodeficiency virus infection. Arch Intern Med. 2000;160:3365-3373.
6.
Thio CL, Seaberg EC, Skolasky RL, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002;360:1921-1926.
7.
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2001;34:1225-1241.
8.
Benhamou Y. Antiretroviral therapy and HIV/hepatitis B virus co-infection. Clin Infect Dis. 2004;38(suppl 2):S98-S103.
9.
Benhamou Y, Katlama C, Lunel F, et al. The effects of lamivudine on replication of hepatitis B virus in HIV infected men. Ann Intern Med. 1996;125:705-712.
10.
Dore GJ, Cooper DA, Barrett C, et al. Dual efficacy of lamivudine treatment in human immunodeficiency virus/hepatitis B virus-coinfected persons in a randomized controlled study (CAESAR). The CAESAR Coordinating Committee. J Infect Dis. 1999;180:607-613.
11.
CAESAR Coordinating Committee. Randomized trial of addition of lamivudine or lamivudine plus loviride to zidovudine containing regimens for patients with HIV-1 infection: the CAESAR trial. Lancet. 1997;349:1413-1421.
12.
Bartholamew MM, Jansen RW, Lennox JJ, et al. Hepatitis-B virus resistance to lamivudine given for recurrent infection after orthopedic liver transplantation. Lancet. 1997;349:20-22.
13.
Ling R, Mutimer D, Ahmed M, et al. Selection of mutations in the hepatitis-B virus polymerase during therapy of transplant recipients with lamivudine. Hepatology. 1996;24:711-713.
14.
Dando T, Plosker G. Adefovir dipivoxil: a review of its use in chronic hepatitis B. Drugs. 2003;63:2215-2234.
15.
Marcellin P, Chang TT, Lim SG, et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen positive chronic hepatitis B. N Engl J Med. 2003;348:800-807.
16.
Benhamou Y, Bochet M, Thiabault V, et al. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine resistant hepatitis B virus: an open label pilot study. Lancet. 2001;358:718-723.
17.
Xiong S, Yang H, Westland C, et al. Resistance surveillance of HBeAg chronic hepatitis B patients treated for two years with adefovir dipivoxil. Abstract presented at: 11th International Symposium on Viral Hepatitis and Liver Disease; April 6-10, 2003; Sydney, Australia. Abstract 779.
18.
Perrillo RP, Schiff ER, Davis GL, et al. A randomized controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group. N Engl J Med. 1990;323:295-301.
19.
Wong DK, Cheung AM, O’Rourke K, et al. Effect of alfa-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. Ann Intern Med. 1993;119:312-323.
20.
Brook MG, Karayiannis P, Thomas HC. Which patients with chronic hepatitis B respond to alpha-interferon therapy? A statistical analysis of predictive factors. Hepatology. 1989;10:761-763.
21.
McDonald JA, Carliso L, Karayiannis P, et al. Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha interferon. Hepatology. 1987;7:719-723.
22.
Perrillo R, Tamburro C, Regenstein F, et al. Low-dose, titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus. Gastroenterology. 1995;109:908-916.
23.
Tenofovir (Viread)[package insert]. Foster City, Calif: Gilead Sciences; 2004.
24.
Emtricitabine (Emtriva)[package insert]. Foster City, Calif: Gilead Sciences; 2004.
25.
Nunez M, Perez-Ormeda M, Diaz B, et al. Activity of tenofovir disoproxil fumarate on hepatitis B virus replication in HIV coinfected patients failing or partially responding to lamivudine. AIDS. 2002;16:2352-2354.
26.
Nelson M, Portsmouth S, Stebbing J, et al. An open-label study of tenofovir disoproxil fumarate in HIV-1 and hepatitis B coinfected individuals. AIDS. 2003;17:F7-F10.
27.
Benhamou Y, Tubiana R, Thiabault V. Tenofovir disoproxil fumarate in patients with HIV and lamivudine resistant virus. N Engl J Med. 2003;348:171-178.
28.
Dore GJ, Cooper DA, Pozniak AL, et al. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naïve and experienced patients coinfected with HIV-1 and hepatitis B virus. JInfect Dis. 2004;189:1185-1192.
29.
Gish R, Leung NW, Wang C, et al. Antiviral activity, safety, and incidence of resistance in chronically infected hepatitis B patients given once daily emtricitabine for 2 years [abstract]. Hepatology. 2002;36(4 pt 2):372A-372A. Abstract 636.
30.
Manns M, McHutchison J, Gordon S, et al. Peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for intinal treatment of hepatitis C: a randomized trial. Lancet. 2001;358:958-965.
31.
Fried M, Shiffman M, Reddy K, et al. Peginterferon alpha-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.
32.
Sharara A, Hunt C, Hamilton J. Hepatitis C. Ann Intern Med. 1996;125:658-668.
33.
Sulkowski M, Thomas D. Hepatitis C in the HIV-infected person. Ann Intern Med. 2003;138:197-207.
34.
Peginterferon alfa-2a (Pegasys) [package insert]. Nutley, NJ: Hoffman-LaRoche; October 2002.
35.
Ribavirin (Copegys)[package insert]. Nutley, NJ: Roche Laboratories; May 2004.
36.
Chung R, Anderson J, Volberding P, et al. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-co-infected persons. N Engl J Med. 2004;351:451-459.
37.
Torriani F, Rodriguez-Torres M, Rockstrohl J, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438-450.
38.
McHutchinson J, Patel K. Future treatment of hepatitis C. Hepatology. 2002;36:S245-S252.
39.
DiBisceglie A, McHutchinson J, Rice C. New therapeutic strategies for hepatitis C. Hepatology. 2002;35:224-231.
40.
Dev A, Patel K, McHutchinson J. Future treatment of hepatitis C: what’s around the corner?Infect Med. 2004;21:28-36.
41.
Leroux-Roels G, Depla E, Hulstaert F, et al. A candidate therapeutic vaccine for chronic hepatitis C infection based on envelope 1 protein: tolerability and immunogenicity in healthy adult volunteers [abstract]. Hepatology. 2000;34(suppl 2):449A-449A.
42.
Albers I, Hartman H, Bircher J, et al. Superiority of the Child-Pugh classification to quantitative liver function tests for assessing prognosis of liver cirrhosis. Sc and J Gastroenterol. 1989;24:269-276.
43.
Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. October 29, 2004. Available at: http://AIDSinfo.nih.gov.
44.
Montaner J, Cote C, Harris M, et al. Nucleoside-related mitochondiral toxicity among HIV-infected patients receiving antiretroviral therapy: insights from the evaluation of venous lactic acid and peripheral blood mitochondrial DNA. Clin Infect Dis. 2004;38(suppl 2):s73-s79.
45.
Stavudine (Zerit)[package insert]. New York, NY: Bristol-Myers Squibb; June 2004.
46.
Didanosine (Videx)[package insert]. New York, NY: Bristol-Myers Squibb; January 2004.
47.
Dieterich D, Robinson P, Love J, et al. Drug-induced liver injury associated with the use of nonnucleoside reverse-transcriptase inhibitors. Clin Infect Dis. 2004;38(suppl 2):S80-S89.
48.
Bourezane Y, Salard D, Hoen B, Vandel S, Drobacheff C, Laurent R. DRESS (drug rash with eosinophilia and systemic symptoms) syndrome associated with nevirapine therapy. Clin Infect Dis. 1998;27:1321-1322.
49.
Fiske WD, Benedek IH, Brennan JM, et al. Pharmacokinetics of efavirenz in subjects with chronic liver disease. Abstract presented at: Sixth Conference on Retroviruses and Opportunistic Infections; February 1999; Chicago, Ill. Abstract 367.
50.
Efavirenz (Sustiva)[package insert]. New York, NY: Bristol Myers Squibb; August 2004.
51.
Sulkowski M, Thomas D, Chaisson R, 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;283:74-80.
52.
Nunez M, Lana R, Mendoza J, et al. Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2001;27:426-431.
53.
Gisolf E, Dreezen C, Danner S, et al, for the Prometheus Study Group. Risk factors for hepatotoxicity in HIV-1 infected patients receiving ritonavir and saquinavir with or without stavudine. Clin Infect Dis. 2000;31:1234-1239.
54.
Sulkowski M. Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors. Clin Infect Dis. 2004;38(suppl 2):S90-S97.
55.
Rutshmann O, Negro F, Hirschel B, et al. Impact of treatment with human immunodeficiency virus (HIV) protease inhibitors on hepatitis C viremia in patients coinfected with HIV. JInfect Dis. 1998;177:783-785.
56.
Benhamou Y, Di Martino V, Bochet M, et al. Factors affecting liver fibrosis in human immunodeficiency virus and hepatitis C virus co-infected patients: impact of protease inhibitor therapy. Hepatology. 2001;34:283-287.
57.
Schapiro JM, Winters MA, Stewart F, et al. The effect of high-dose saquinavir on viral load and CD4+ T-cell counts in HIV-infected patients. Ann Intern Med. 1996;124:1039-1050.
58.
Danner SA, Carr A, Leonard JM, et al, for the European-Australian Collaborative Ritonavir Study Group. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N Engl J Med. 1995;333:1528-1533.
59.
Marzolini C, Telenti A, Decosterd LA, Greub G, Biollaz J, Buclin T. Efavirenz plasma levels can predict treatment failure and central nervous system side effect in HIV-1-infected patients. AIDS. 2001;15:71-75.
60.
Molla A, Korneyeva M, Gao Q, et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med. 1996;2:760-766.
61.
Hsu A, Granneman GR, Witt G, et al. Multiple-dose pharmacokinetics of ritonavir in human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 1997;41:898-905.
62.
Stein DS, Fish DG, Bilello JA, Preston SL, Martineau GL, Drusano GL. A 24-week open-label phase I/II evaluation of the HIV protease inhibitor MK-639 (indinavir). AIDS. 1996;10:485-492.
63.
Harris M, Durakovic C, Rae S, et al. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis. 1998;177:1514-1520.
64.
Murphy R, Sommadossi JP, Lamson M, Hall DB, Myers M, Dusek A. Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons with human immunodeficiency virus type 1. J Infect Dis. 1999;179:1116-1123.
65.
Burger DM, Hoetelmans RMW, Mulder JW, et al. Low plasma levels of indinavir (IDV) are highly predictive of virological treatment failure in patinets using IDV-containing triple therapy. Abstract presented at: 12th World AIDS Conference; June 28-July 3, 1998; Geneva, Switzerland. Abstract 42275.
66.
Pithavala Y, Zhang M, Knowles M, Daniels R, Anderson R, Kerr B. Virologic response-plasma concentration relationship in phase III study of nelfinavir mesylate. Abstract presented at: 12th World AIDS Conference; June 28-July 3, 1998; Geneva, Switzerland. Abstract 12304.
67.
Lorenzi P, Yerly S, Abderrakim K, et al. Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir and saquinavir. AIDS. 1997;11:F95-F99.
68.
Sadler BM, Gillotin C, Stein DS. Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing. Antimicrob Agents Chemother. 2001;45:30-37.
69.
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. 2000;14:1333-1339.
70.
Levin J. Hepatitis C virus (HCV) and HCV/HIV co-infection handbook. Version IV. National Aids Treatment Advocacy Project (NATAP). December 18, 2002. Available at: http://www.natap.org.
71.
De Luca, Andrea MD, Bugarini R, et al. Coinfection with hepatitis viruses and outcome of initial antiretroviral regimens in previously naïve HIV-infected subjects. Arch Intern Med. 2002;162:2125-2132.
72.
den Brinker M, Wit F, Wertheim-vanDillen P, 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;14:2895-2902.
73.
Malavaud B, Dinh B, Bonnet E, et al. Increased incidence of indinavir nephrolithiasis in patients with hepatitis B or C virus infection. Antiretroviral Ther. 2000;5:3-5.
