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Treatment of chronic hepatitis B in the HIV-infected patient

Kenneth E Sherman, MD, PhD
Chloe L Thio, MD
Section Editor
David L Thomas, MD
Deputy Editor
Jennifer Mitty, MD, MPH


The use of potent antiretroviral therapy (ART) to treat HIV infection has led to declining rates of opportunistic infections and the need to manage other causes of morbidity in HIV-infected individuals, such as end-stage liver disease secondary to chronic hepatitis B virus (HBV) infection. The treatment and prevention of HBV infection has taken on great significance in light of the negative impact HIV has on the natural history of chronic HBV infection. In coinfected patients, HBV infection is best treated with oral antiviral agents that can also be used to treat HIV. Once initiated, they are continued indefinitely in most individuals to maintain suppression of both viruses.

This topic will review the treatment of chronic HBV infection in the HIV-infected host. Other relevant topics include:

(See "Epidemiology, clinical manifestations, and diagnosis of hepatitis B in the HIV-infected patient".)

(See "Pretreatment evaluation of chronic hepatitis B virus infection in the HIV-infected patient".)

(See "Monitoring the HIV-infected patient with chronic hepatitis B virus infection".)


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Literature review current through: Sep 2016. | This topic last updated: Oct 7, 2016.
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  1. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguideline s/adult_oi.pdf (Accessed on November 04, 2015).
  2. Günthard HF, Saag MS, Benson CA, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel. JAMA 2016; 316:191.
  3. European guidelines for treatment of HIV-infected adults. http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html (Accessed on January 14, 2015).
  4. World Health Organization. Guidelines for the prevention, care and treatment of persons living with chronic hepatitis B http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf?ua=1 (Accessed on March 23, 2015).
  5. 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://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf (Accessed on July 14, 2016).
  6. Stockdale AJ, Phillips RO, Beloukas A, et al. Liver Fibrosis by Transient Elastography and Virologic Outcomes After Introduction of Tenofovir in Lamivudine-Experienced Adults With HIV and Hepatitis B Virus Coinfection in Ghana. Clin Infect Dis 2015; 61:883.
  7. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013; 381:468.
  8. Soriano V, Poveda E, Vispo E, Barreiro P. Hepatitis B in HIV-infected patients. Clin Liver Dis 2013; 17:489.
  9. Colin JF, Cazals-Hatem D, Loriot MA, et al. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology 1999; 29:1306.
  10. Di Martino V, Thevenot T, Colin JF, et al. Influence of HIV infection on the response to interferon therapy and the long-term outcome of chronic hepatitis B. Gastroenterology 2002; 123:1812.
  11. Thio CL. Hepatitis B and human immunodeficiency virus coinfection. Hepatology 2009; 49:S138.
  12. Puoti M, Torti C, Bruno R, et al. Natural history of chronic hepatitis B in co-infected patients. J Hepatol 2006; 44:S65.
  13. Thio CL, Seaberg EC, Skolasky R Jr, et al. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet 2002; 360:1921.
  14. Puoti M, Spinetti A, Ghezzi A, et al. Mortality for liver disease in patients with HIV infection: a cohort study. J Acquir Immune Defic Syndr 2000; 24:211.
  15. 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; 19:593.
  16. Crane M, Oliver B, Matthews G, et al. Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy. J Infect Dis 2009; 199:974.
  17. Cohen Stuart JW, Velema M, Schuurman R, et al. Occult hepatitis B in persons infected with HIV is associated with low CD4 counts and resolves during antiretroviral therapy. J Med Virol 2009; 81:441.
  18. Price H, Dunn D, Pillay D, et al. Suppression of HBV by tenofovir in HBV/HIV coinfected patients: a systematic review and meta-analysis. PLoS One 2013; 8:e68152.
  19. Boyd A, Lasnier E, Molina JM, et al. Liver fibrosis changes in HIV-HBV-coinfected patients: clinical, biochemical and histological effect of long-term tenofovir disoproxil fumarate use. Antivir Ther 2010; 15:963.
  20. Martín-Carbonero L, Teixeira T, Poveda E, et al. Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analogues. AIDS 2011; 25:73.
  21. Puoti M, Cozzi-Lepri A, Paraninfo G, et al. Impact of lamivudine on the risk of liver-related death in 2,041 HBsAg- and HIV-positive individuals: results from an inter-cohort analysis. Antivir Ther 2006; 11:567.
  22. Benhamou Y, Tubiana R, Thibault V. Tenofovir disoproxil fumarate in patients with HIV and lamivudine-resistant hepatitis B virus. N Engl J Med 2003; 348:177.
  23. Dore GJ, Cooper DA, Pozniak AL, et al. Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus. J Infect Dis 2004; 189:1185.
  24. Núñez M, Pérez-Olmeda M, Díaz B, et al. Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine. AIDS 2002; 16:2352.
  25. Nelson M, Portsmouth S, Stebbing J, et al. An open-label study of tenofovir in HIV-1 and Hepatitis B virus co-infected individuals. AIDS 2003; 17:F7.
  26. Ristig MB, Crippin J, Aberg JA, et al. Tenofovir disoproxil fumarate therapy for chronic hepatitis B in human immunodeficiency virus/hepatitis B virus-coinfected individuals for whom interferon-alpha and lamivudine therapy have failed. J Infect Dis 2002; 186:1844.
  27. Bihl F, Martinetti G, Wandeler G, et al. HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons. BMC Gastroenterol 2015; 15:79.
  28. Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015; 385:2606.
  29. Murakami E, Wang T, Park Y, et al. Implications of efficient hepatic delivery by tenofovir alafenamide (GS-7340) for hepatitis B virus therapy. Antimicrob Agents Chemother 2015; 59:3563.
  30. Agarwal K, Fung SK, Nguyen TT, et al. Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection. J Hepatol 2015; 62:533.
  31. Liu Y, Mitchell BC, Dinh P, et al. Antiviral activity of tenofovir alafenamide (TAF) against drug resistant HBV isolates in vitro. Presented at the American Association for the Study of Liver Diseases. San Francisco. 2015
  32. Gallant J, Brunetta J, Crofoot G, et al. Efficacy and Safety of Switching to a Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) in HIV-1/Hepatitis B Coinfected Adults. J Acquir Immune Defic Syndr 2016.
  33. Chan HLY et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016 Sep 22
  34. Buti M et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016 Sep 22;
  35. Tenney DJ, Rose RE, Baldick CJ, et al. Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology 2009; 49:1503.
  36. Hoff J, Bani-Sadr F, Gassin M, Raffi F. Evaluation of chronic hepatitis B virus (HBV) infection in coinfected patients receiving lamivudine as a component of anti-human immunodeficiency virus regimens. Clin Infect Dis 2001; 32:963.
  37. Snow, A, Harris, J, Borroto-Esoda, K, et al. Emtricitabine therapy for hepatitis infection in HIV+ patients co-infected with hepatitis B virus: efficacy and genotypic findings in antiretroviral treatment-naive patients. Presented at the 11th Conference on Retroviruses and Opportunistic Infections, Boston, MA Abstract #836.
  38. 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.
  39. Benhamou Y, Katlama C, Lunel F, et al. Effects of lamivudine on replication of hepatitis B virus in HIV-infected men. Ann Intern Med 1996; 125:705.
  40. Matthews GV, Bartholomeusz A, Locarnini S, et al. Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy. AIDS 2006; 20:863.
  41. Benhamou Y, Bochet M, Thibault V, et al. Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients. Hepatology 1999; 30:1302.
  42. Bessesen M, Ives D, Condreay L, et al. Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine. Clin Infect Dis 1999; 28:1032.
  43. Locarnini S, Warner N. Major causes of antiviral drug resistance and implications for treatment of hepatitis B virus monoinfection and coinfection with HIV. Antivir Ther 2007; 12 Suppl 3:H15.
  44. Yeh CT, Chien RN, Chu CM, Liaw YF. Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy. Hepatology 2000; 31:1318.
  45. Benhamou Y, Bochet M, Thibault 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.
  46. Benhamou Y, Thibault V, Vig P, et al. Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1. J Hepatol 2006; 44:62.
  47. Piroth L, Sène D, Pol S, et al. Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY). AIDS 2007; 21:1323.
  48. Marcellin P, Boyer N, Colin JF, et al. Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine. Gut 1993; 34:S106.
  49. Hoofnagle JH, Peters M, Mullen KD, et al. Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B. Gastroenterology 1988; 95:1318.
  50. Brook MG, McDonald JA, Karayiannis P, et al. Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response. Gut 1989; 30:1116.
  51. Brook MG, Chan G, Yap I, et al. Randomised controlled trial of lymphoblastoid interferon alfa in Europid men with chronic hepatitis B virus infection. BMJ 1989; 299:652.
  52. Wong DK, Yim C, Naylor CD, et al. Interferon alfa treatment of chronic hepatitis B: randomized trial in a predominantly homosexual male population. Gastroenterology 1995; 108:165.
  53. Porchon C, Kremsdorf D, Pol S, et al. Serum hepatitis C virus RNA and hepatitis B virus DNA in non-A, non-B post-transfusional and sporadic chronic hepatitis. J Hepatol 1992; 16:184.
  54. Bartholomeusz A, Locarnini SA. Antiviral drug resistance: clinical consequences and molecular aspects. Semin Liver Dis 2006; 26:162.
  55. Tenney DJ, Levine SM, Rose RE, et al. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. Antimicrob Agents Chemother 2004; 48:3498.
  56. HHS Panel on antiretroviral guidelines for adults and adolescents includes a fixed-dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide among the recommended regimens for antiretroviral treatment-naive individuals with HIV-1 infection. https://aidsinfo.nih.gov/news/1621/evg-c-ftc-taf-statement-from-adult-arv-guideline-panel (Accessed on November 20, 2015).
  57. Altfeld M, Rockstroh JK, Addo M, et al. Reactivation of hepatitis B in a long-term anti-HBs-positive patient with AIDS following lamivudine withdrawal. J Hepatol 1998; 29:306.
  58. McGovern B. What drives hepatitis B virus-related hepatic flares? Virus, T cells--or a bit of both? Clin Infect Dis 2004; 39:133.
  59. Dore GJ, Soriano V, Rockstroh J, et al. Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption. AIDS 2010; 24:857.
  60. Bellini C, Keiser O, Chave JP, et al. Liver enzyme elevation after lamivudine withdrawal in HIV-hepatitis B virus co-infected patients: the Swiss HIV Cohort Study. HIV Med 2009; 10:12.
  61. Terrault NA, Bzowej NH, Chang KM, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016; 63:261.
  62. Mikulska M, Taramasso L, Giacobbe DR, et al. Case report: management and HBV sequencing in a patient co-infected with HBV and HIV failing tenofovir. J Med Virol 2012; 84:1340.
  63. Ratcliffe L, Beadsworth MB, Pennell A, et al. Managing hepatitis B/HIV co-infected: adding entecavir to truvada (tenofovir disoproxil/emtricitabine) experienced patients. AIDS 2011; 25:1051.
  64. Yang YJ, Shim JH, Kim KM, et al. Assessment of current criteria for primary nonresponse in chronic hepatitis B patients receiving entecavir therapy. Hepatology 2014; 59:1303.
  65. Tourret J, Deray G, Isnard-Bagnis C. Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword? J Am Soc Nephrol 2013; 24:1519.
  66. Gupta SK. Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system. AIDS Patient Care STDS 2008; 22:99.