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艾滋病病毒感染者丙型肝炎病毒感染的治疗

Author
Jürgen Kurt Rockstroh, MD
Section Editor
David L Thomas, MD
Deputy Editor
Allyson Bloom, MD
Translators
张绪清, 主任医师，教授

引言

艾滋病病毒感染者发生丙型肝炎病毒(hepatitis C virus, HCV)感染的后果较为严重，包括肝病进展加速、终末期肝病发生率较高，以及肝功能失代偿后寿命缩短，特别是对于更晚期的免疫缺陷患者[1]。在强效抗逆转录病毒治疗(antiretroviral therapy, ART)的时代，终末期肝病仍是共感染HCV的艾滋病病毒感染者死亡的一个重大原因[2,3]。

本专题将介绍人类免疫缺陷病毒(human immunodeficiency virus, HIV)/HCV共感染患者的治疗。这类患者人群的流行病学、自然病程、诊断和评估将在别处讨论。 (参见“HIV感染者中丙型肝炎的流行病学、自然病程与诊断”和“慢性丙型肝炎病毒感染的HIV感染者的评估”)

指南

美国肝病研究协会(American Association for the Study of Liver Diseases, AASLD)与美国感染病学会(Infectious Diseases Society of America, IDSA)在2014年联合发布了HCV感染的诊断和治疗指南，在国际抗病毒学会-美国的协作下，该指南正在持续更新，该指南可通过www.hcvguidelines.org获取[4]。另外，美国卫生与公共服务部的指南就成人和青少年抗逆转录病毒药物的应用对共感染的治疗进行了详述[5]。本专题所讨论的内容基本与这些指南基本一致。

此外，欧洲肝脏研究协会(European Association for the Study of the Liver, EASL)HCV指南在2015年进行了更新[6]，欧洲临床艾滋病学会的共感染指南在2014年进行了更新[7]。

定义

根据患者的暴露情况和既往的治疗反应，已采用了具体的术语来界定患者人群：

                              

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Literature review current through: 2017-06 . | This topic last updated: 2017-03-13.
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References
Top
  1. McGovern BH. Hepatitis C in the HIV-infected patient. J Acquir Immune Defic Syndr 2007; 45 Suppl 2:S47.
  2. Weber R, Sabin CA, Friis-Møller N, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med 2006; 166:1632.
  3. Smith CJ, Ryom L, Weber R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet 2014; 384:241.
  4. Recommendations for Testing, Managing, and Treating Hepatitis C. Joint panel from the American Association of the Study of Liver Diseases and the Infectious Diseases Society of America. http://www.hcvguidelines.org/ (Accessed on August 01, 2016).
  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 April 08, 2015).
  6. European Association for the Study of the Liver Recommendations on Treatment of Hepatitis C 2015. http://www.easl.eu/medias/cpg/HEPC-2015/Full-report.pdf (Accessed on July 17, 2015).
  7. European AIDS Clinical Society Guidelines. Version 7.1, November 2014. http://www.eacsociety.org/files/guidelines_english_71_141204.pdf (Accessed on January 29, 2015).
  8. Swain MG, Lai MY, Shiffman ML, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010; 139:1593.
  9. Martinot-Peignoux M, Stern C, Maylin S, et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology 2010; 51:1122.
  10. Labarga P, Soriano V, Vispo ME, et al. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. J Infect Dis 2007; 196:670.
  11. Chung RT, Andersen J, Volberding P, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med 2004; 351:451.
  12. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med 2004; 351:438.
  13. Soriano V, Labarga P, Ruiz-Sancho A, et al. Regression of liver fibrosis in hepatitis C virus/HIV-co-infected patients after treatment with pegylated interferon plus ribavirin. AIDS 2006; 20:2225.
  14. Lissen E, Clumeck N, Sola R, et al. Histological response to pegIFNalpha-2a (40KD) plus ribavirin in HIV-hepatitis C virus co-infection. AIDS 2006; 20:2175.
  15. Rodríguez-Torres M, Rodríguez-Orengo JF, Ríos-Bedoya CF, et al. Effect of hepatitis C virus treatment in fibrosis progression rate (FPR) and time to cirrhosis (TTC) in patients co-infected with human immunodeficiency virus: a paired liver biopsy study. J Hepatol 2007; 46:613.
  16. Barreiro P, Labarga P, Martín-Carbonero L, et al. Sustained virological response following HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients. Antivir Ther 2006; 11:869.
  17. Soriano V, Maida I, Núñez M, et al. Long-term follow-up of HIV-infected patients with chronic hepatitis C virus infection treated with interferon-based therapies. Antivir Ther 2004; 9:987.
  18. Berenguer J, Alvarez-Pellicer J, Martín PM, et al. Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology 2009; 50:407.
  19. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. 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.
  20. Cooper CL. De-"Liver"-ing HIV/hepatitis C virus-coinfected patients from antiretroviral hepatotoxicity. J Infect Dis 2007; 196:656.
  21. Mira JA, Rivero-Juárez A, López-Cortés LF, et al. Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis. Clin Infect Dis 2013; 56:1646.
  22. Berenguer J, Zamora FX, Carrero A, et al. Effects of sustained viral response in patients with HIV and chronic hepatitis C and nonadvanced liver fibrosis. J Acquir Immune Defic Syndr 2014; 66:280.
  23. Berenguer J, Alvarez-Pellicer J, Carrero A, et al. Clinical effects of viral relapse after interferon plus ribavirin in patients co-infected with human immunodeficiency virus and hepatitis C virus. J Hepatol 2013; 58:1104.
  24. McHutchison JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998; 339:1485.
  25. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA 2004; 292:2839.
  26. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958.
  27. Núñez M, Miralles C, Berdún MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retroviruses 2007; 23:972.
  28. Vogel M, Ahlenstiel G, Hintsche B, et al. The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive Individuals. Eur J Med Res 2010; 15:102.
  29. Sulkowski MS, Sherman KE, Dieterich DT, et al. Combination therapy with telaprevir for chronic hepatitis C virus genotype 1 infection in patients with HIV: a randomized trial. Ann Intern Med 2013; 159:86.
  30. Sulkowski M, Pol S, Mallolas J, et al. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis 2013; 13:597.
  31. Dieterich D, Rockstroh JK, Orkin C, et al. Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study. Clin Infect Dis 2014; 59:1579.
  32. Sulkowski MS, Naggie S, Lalezari J, et al. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. JAMA 2014; 312:353.
  33. Rodriguez-Torres M, Rodriguez-Orengo J, Gaggar A, et al. Sofosbuvir and peginterferon alfa-2a/ribavirin for treatment-naive genotype 1-4 HCV-infected patients who are coinfected with HIV. Presented at IDWeek 2013, San Francisco, CA, October 2-6, 2013.
  34. Dieterich D, Nelson M, Soriano V, et al. Faldaprevir and pegylated interferon α-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV. AIDS 2015; 29:571.
  35. Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA 2015; 313:1232.
  36. Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA 2015; 313:1223.
  37. Christensen S, Ingiliz P, Hueppe D, et al. German cohort on sofosbuvir based therapy for HCV/HIV- and HCV-infection (GESOCO). Presented at the 22st Conference on Retroviruses and Opportunistic Infections, Seattle, WA, February 23-26, 2015. Abstract #646.
  38. del Bello D, Bichoupan K, Levine C, et al. Real-world data on HIV-positive patients with HCV treatment with sofosbuvir and/or simeprevir. Presented at the 22st Conference on Retroviruses and Opportunistic Infections, Seattle, WA, February 23-26, 2015. Abstract # 647.
  39. Gilmore J, Lynn K, Breen D, et al. Effectiveness of sofosbuvir/simeprevir for HIV/HCV patients in clinical practice. Presented at the 22st Conference on Retroviruses and Opportunistic Infections, Seattle, WA, February 23-26, 2015.
  40. http://www.retroconference.org/2011/Abstracts/42467.htm (Accessed on June 13, 2011).
  41. Basu P, Shah N, Aloysius M. Simeprevir and sofosbuvir with modified doses of ribavirin therapy on telaprevir-experience coinfeced (with HIV) cirrhotics with chronic hepatitis C: A randomized open label clinical pilot study: STOP C. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014. Abstract #993.
  42. Rockstroh JK, Puoti M, Rodriguez-Torres M, et al. Sofosbuvir and ribavirin therapy for the treatment of HIV/HCV coinfected patients with HCV GT1-4 infection: The PHOTON-1 and 2 trials. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014. Abstract #195.
  43. Naggie S, Cooper C, Saag M, et al. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med 2015; 373:705.
  44. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med 2015; 373:714.
  45. Molina JM, Orkin C, Iser DM, et al. Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet 2015; 385:1098.
  46. Jacobson IM, Gordon SC, Kowdley KV, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013; 368:1867.
  47. Lawitz E. Poordad F, Brainard DM, et al. Sofosbuvir in combination with PegIFN and ribavirin for 12 weeks provides high SVR rates in HCV-infected genotype 2 or 3 treatment-experienced patients with and without compensated cirrhosis: Results from the LONESTAR-2 study. Presented at the 64th annual meeting of the American Association for the Study of Liver Diseases, Washington, DC, November 1-5, 2013.
  48. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015; 61:1127.
  49. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med 2013; 368:1878.
  50. Foster G, Pianko S, Cooper C, et al. Sofosbuvir plus peginterferon/ribavirin for 12 weeks vs sofosbuvir plus ribavirin for 16 or 24 weeks in genotype 3 infected patients and treatment-experienced cirrhostic patients with genotype 2 HCV: The Boson study. Presented at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL), Vienna Austria, April 22-26, 2015. Abstract # L05
  51. Naggie S, Cooper C, Saag M, et al. Ledipasvir/sofosbuvir for 12 weeks in patients coinfected with HCV and HIV-1. Presented at the 22st Conference on Retroviruses and Opportunistic Infections, Seattle, WA, February 23-26, 2015. Abstract #152LB
  52. Rodríguez-Nóvoa S, Morello J, González M, et al. Increase in serum bilirubin in HIV/hepatitis-C virus-coinfected patients on atazanavir therapy following initiation of pegylated-interferon and ribavirin. AIDS 2008; 22:2535.
  53. Balzarini J, Lee CK, Herdewijn P, De Clercq E. Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus. J Biol Chem 1991; 266:21509.
  54. Mauss S. Treatment of viral hepatitis in HIV-coinfected patients-adverse events and their management. J Hepatol 2006; 44:S114.
  55. McGovern B, Bica I. Risk of HAART therapy in hepatitis C. Hepatology 2002; 35:730.
  56. Vispo E, Barreiro P, Pineda JA, et al. Low response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C treated with abacavir. Antivir Ther 2008; 13:429.
  57. Mira JA, López-Cortés LF, Barreiro P, et al. Efficacy of pegylated interferon plus ribavirin treatment in HIV/hepatitis C virus co-infected patients receiving abacavir plus lamivudine or tenofovir plus either lamivudine or emtricitabine as nucleoside analogue backbone. J Antimicrob Chemother 2008; 62:1365.
  58. Laufer N, Laguno M, Perez I, et al. Abacavir does not influence the rate of virological response in HIV-HCV-coinfected patients treated with pegylated interferon and weight-adjusted ribavirin. Antivir Ther 2008; 13:953.
  59. Berenguer J, von Wichmann MA, Quereda C, et al. Effect of accompanying antiretroviral drugs on virological response to pegylated interferon and ribavirin in patients co-infected with HIV and hepatitis C virus. J Antimicrob Chemother 2011; 66:2843.
  60. Harvoni (ledipasvir-sofosbuvir). US FDA approved product information. National Library of Medicine.
  61. German P, Pang PS, Fang L, et al. Drug-drug interaction profile of the fixed-dose combination tablet ledipasvir/sofosbuvir. Presented at the American Association for the Study of Liver Diseases Liver Meeting, Boston MA, November 7-11, 2014. Abstract #1976.
  62. VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets). US FDA approved product information. National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on January 01, 2015).
  63. Khatri A, Wang W, Podsadecki T, et al. Drug-drug interactions of the direct acting antiviral regimen of ABT-450/r, ombitasvir and dasabuvir with emtricitabine+tenofovir, raltegravir, rilpivirine and efavirenz. Presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 5-9, 2014; Washington, DC.
  64. Thomas DL, Bartlett JG, Peters MG, et al. Provisional guidance on the use of hepatitis C virus protease inhibitors for treatment of hepatitis C in HIV-infected persons. Clin Infect Dis 2012; 54:979.
  65. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm291144.htm (Accessed on February 10, 2012).
  66. de Kanter CT, Blonk MI, Colbers AP, et al. Lack of a clinically significant drug-drug interaction in healthy volunteers between the hepatitis C virus protease inhibitor boceprevir and the HIV integrase inhibitor raltegravir. Clin Infect Dis 2013; 56:300.
  67. Hammond KP, Wolfe P, Burton JR Jr, et al. Pharmacokinetic interaction between boceprevir and etravirine in HIV/HCV seronegative volunteers. J Acquir Immune Defic Syndr 2013; 62:67.
  68. Vourvahis M, Plotka A, Kantaridis Cet al. The effect of boceprevir and telaprevir on the pharmacokinetics of maraviroc: an open-label, fixed-sequence study in healthy volunteers. Presented at the 14th International Workshop on Clinical Pharmacology of HIV Therapy, Amsterdam, April 22-24, 2013, Abstract O_17.
  69. http://www.retroconference.org/2012b/Abstracts/45378.htm (Accessed on April 30, 2012).
  70. Rhee E, Feng H-P, Xuan F, et al. Absence of a significant pharmacokinetic interaction between the hepatitis C virus protease inhibitor boceprevir and HIV-1 NNRTI rilpivirine. Presented at the 20th Conference on Retroviruses and Opportunistic Infections, Atlanta, GA, March 3-6, 2013; abstract #537
  71. Schwarze-Zander C, Rockstroh JK. HIV protease inhibitors in combination with boceprevir: are drug-drug interactions the same for all patients? AIDS 2012; 26:1845.
  72. http://www.hep-druginteractions.org/ (Accessed on September 05, 2013).
  73. Fleming CA, Craven DE, Thornton D, et al. Hepatitis C virus and human immunodeficiency virus coinfection in an urban population: low eligibility for interferon treatment. Clin Infect Dis 2003; 36:97.
  74. Mehta SH, Lucas GM, Mirel LB, et al. Limited effectiveness of antiviral treatment for hepatitis C in an urban HIV clinic. AIDS 2006; 20:2361.
  75. Butt AA, Khan UA, Shaikh OS, et al. Rates of HCV treatment eligibility among HCV-monoinfected and HCV/HIV-coinfected patients in tertiary care referral centers. HIV Clin Trials 2009; 10:25.
  76. Taylor LE, Schwartzapfel B, Allen S, et al. Extending treatment for HCV infection to HIV-HCV coinfected individuals with psychiatric illness and drug dependence. Clin Infect Dis 2003; 36:1501.