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Epidemiology, natural history, and diagnosis of hepatitis C in the HIV-infected patient

Author
Arthur Y Kim, MD, FIDSA
Section Editor
David L Thomas, MD
Deputy Editor
Allyson Bloom, MD

INTRODUCTION

The intersection of the HIV and hepatitis C virus (HCV) epidemics has significant clinical implications and raises many challenging issues for patients and their health care providers [1]. A thorough understanding of the natural history of liver disease in this complex patient population is critical for optimal management.

The epidemiology, natural history, and diagnosis of hepatitis C in the HIV-infected patient will be discussed here. (See "Evaluation of the HIV-infected patient with chronic hepatitis C virus infection" and "Treatment of hepatitis C virus infection in the HIV-infected patient".)

VIROLOGY OF HCV

Viral kinetics — HIV (a retrovirus) and HCV (a flavivirus) are RNA viruses. The viral kinetics of HIV and HCV have been determined by perturbation of the steady-state between virus production and clearance with potent antiviral agents [2,3]. HIV viral production rates approximate 10(10) virions a day with a half-life of less than six hours [2]. Virion production rates are even greater with HCV, approaching 10(12) virions a day with a virion half-life of 2.7 hours [3].

Viral load — During the chronic stage of either HIV or HCV infection, a relatively stable viral load or "set point" is maintained [4,5]. However, in the setting of combined infection, HCV RNA levels increase after HIV seroconversion and continue to increase over time compared with patients with HCV alone [6,7]. The level of HCV viremia is inversely correlated with lower CD4 counts in most, but not all studies [7,8] and may transiently increase with initiation of antiretroviral therapy (ART) or heavy alcohol use [9]. Overall increases in the HCV viral load do not have implications for the severity of liver-related disease, but do have an impact on treatment response. (See "Evaluation of the HIV-infected patient with chronic hepatitis C virus infection".)

One study evaluated whether higher levels of HCV viremia in HIV-infected patients may be related to immunosuppression [10]. The researchers reasoned that if high levels of replication were due to decreased immune selective pressure, then a reduced rate of nucleotide changes would be expected within the virus itself. However, in an investigation of HCV envelope sequences in 79 patients, with or without HIV coinfection, no significant divergence was demonstrated over time between the two groups. Another way HIV infection may increase HCV replication is through the virus itself; one in vitro study demonstrated that the envelope protein of HIV (gp120) increased HCV replication through engagement of cellular coreceptors of HIV (ie, CXCR4 or CCR5) [11].

                              

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Literature review current through: Nov 2016. | This topic last updated: Mon Dec 01 00:00:00 GMT+00:00 2014.
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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. Ho DD, Neumann AU, Perelson AS, et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995; 373:123.
  3. Neumann AU, Lam NP, Dahari H, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282:103.
  4. Piatak M Jr, Saag MS, Yang LC, et al. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science 1993; 259:1749.
  5. Nguyen TT, Sedghi-Vaziri A, Wilkes LB, et al. Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection. J Viral Hepat 1996; 3:75.
  6. Thomas DL, Shih JW, Alter HJ, et al. Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users. J Infect Dis 1996; 174:690.
  7. Daar ES, Lynn H, Donfield S, et al. Relation between HIV-1 and hepatitis C viral load in patients with hemophilia. J Acquir Immune Defic Syndr 2001; 26:466.
  8. Ghany MG, Leissinger C, Lagier R, et al. Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs. Dig Dis Sci 1996; 41:1265.
  9. Cooper CL, Cameron DW. Effect of alcohol use and highly active antiretroviral therapy on plasma levels of hepatitis C virus (HCV) in patients coinfected with HIV and HCV. Clin Infect Dis 2005; 41 Suppl 1:S105.
  10. Netski DM, Mao Q, Ray SC, Klein RS. Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression. J Acquir Immune Defic Syndr 2008; 49:136.
  11. Lin W, Weinberg EM, Tai AW, et al. HIV increases HCV replication in a TGF-beta1-dependent manner. Gastroenterology 2008; 134:803.
  12. Goutagny N, Fatmi A, De Ledinghen V, et al. Evidence of viral replication in circulating dendritic cells during hepatitis C virus infection. J Infect Dis 2003; 187:1951.
  13. Blackard JT, Kemmer N, Sherman KE. Extrahepatic replication of HCV: insights into clinical manifestations and biological consequences. Hepatology 2006; 44:15.
  14. Lanford RE, Chavez D, Chisari FV, Sureau C. Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR. J Virol 1995; 69:8079.
  15. Blackard JT, Smeaton L, Hiasa Y, et al. Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons. J Infect Dis 2005; 192:258.
  16. Laskus T, Radkowski M, Piasek A, et al. Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: evidence of active replication in monocytes/macrophages and lymphocytes. J Infect Dis 2000; 181:442.
  17. Goletti D, Weissman D, Jackson RW, et al. Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation. J Immunol 1996; 157:1271.
  18. Graham CS, Koziel MJ. Why should hepatitis C affect immune reconstitution in HIV-1-infected patients? Lancet 2000; 356:1865.
  19. Minosse C, Calcaterra S, Abbate I, et al. Possible compartmentalization of hepatitis C viral replication in the genital tract of HIV-1-coinfected women. J Infect Dis 2006; 194:1529.
  20. Nowicki MJ, Laskus T, Nikolopoulou G, et al. Presence of hepatitis C virus (HCV) RNA in the genital tracts of HCV/HIV-1-coinfected women. J Infect Dis 2005; 192:1557.
  21. Holland JJ, De La Torre JC, Steinhauer DA. RNA virus populations as quasispecies. Curr Top Microbiol Immunol 1992; 176:1.
  22. Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 1995; 267:483.
  23. Havlir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med 1996; 124:984.
  24. Davis GL. Hepatitis C virus genotypes and quasispecies. Am J Med 1999; 107:21S.
  25. Sherman KE, Andreatta C, O'Brien J, et al. Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain. Hepatology 1996; 23:688.
  26. Speck RF, Wehrly K, Platt EJ, et al. Selective employment of chemokine receptors as human immunodeficiency virus type 1 coreceptors determined by individual amino acids within the envelope V3 loop. J Virol 1997; 71:7136.
  27. Toyoda H, Kumada T, Nakano S, et al. Quasispecies nature of hepatitis C virus and response to alpha interferon: significance as a predictor of direct response to interferon. J Hepatol 1997; 26:6.
  28. Sherman KE, Rouster SD, Stanford S, et al. Hepatitis C virus (HCV) quasispecies complexity and selection in HCV/HIV-coinfected subjects treated with interferon-based regimens. J Infect Dis 2010; 201:712.
  29. Blackard JT, Hiasa Y, Smeaton L, et al. Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection. J Infect Dis 2007; 195:1765.
  30. McGovern BH, Abu Dayyeh BK, Chung RT. Avoiding therapeutic pitfalls: the rational use of specifically targeted agents against hepatitis C infection. Hepatology 2008; 48:1700.
  31. Kuntzen T, Timm J, Berical A, et al. Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients. Hepatology 2008; 48:1769.
  32. Gaudieri S, Rauch A, Pfafferott K, et al. Hepatitis C virus drug resistance and immune-driven adaptations: relevance to new antiviral therapy. Hepatology 2009; 49:1069.
  33. Staples CT Jr, Rimland D, Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta V.A. (Veterans Affairs Medical Center) Cohort Study (HAVACS): the effect of coinfection on survival. Clin Infect Dis 1999; 29:150.
  34. Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C Virus prevalence among patients infected with Human Immunodeficiency Virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis 2002; 34:831.
  35. Garfein RS, Vlahov D, Galai N, et al. Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses. Am J Public Health 1996; 86:655.
  36. Kim AY, Chung RT. Coinfection with HIV-1 and HCV--a one-two punch. Gastroenterology 2009; 137:795.
  37. Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990; 264:2231.
  38. Thomas DL, Zenilman JM, Alter HJ, et al. Sexual transmission of hepatitis C virus among patients attending sexually transmitted diseases clinics in Baltimore--an analysis of 309 sex partnerships. J Infect Dis 1995; 171:768.
  39. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000; 342:921.
  40. Osmond DH, Padian NS, Sheppard HW, et al. Risk factors for hepatitis C virus seropositivity in heterosexual couples. JAMA 1993; 269:361.
  41. Tohme RA, Holmberg SD. Is sexual contact a major mode of hepatitis C virus transmission? Hepatology 2010; 52:1497.
  42. Eyster ME, Alter HJ, Aledort LM, et al. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med 1991; 115:764.
  43. Soto B, Rodrigo L, Garcia-Bengoechea M, et al. Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency virus infection in the index case. A multicentre study of 423 pairings. J Intern Med 1994; 236:515.
  44. Wyld R, Robertson JR, Brettle RP, et al. Absence of hepatitis C virus transmission but frequent transmission of HIV-1 from sexual contact with doubly-infected individuals. J Infect 1997; 35:163.
  45. Garg S, Taylor LE, Grasso C, Mayer KH. Prevalent and incident hepatitis C virus infection among HIV-infected men who have sex with men engaged in primary care in a Boston community health center. Clin Infect Dis 2013; 56:1480.
  46. Raymond HF, Hughes A, O'Keefe K, et al. Hepatitis C prevalence among HIV-positive MSM in San Francisco: 2004 and 2008. Sex Transm Dis 2011; 38:219.
  47. Osmond DH, Charlebois E, Sheppard HW, et al. Comparison of risk factors for hepatitis C and hepatitis B virus infection in homosexual men. J Infect Dis 1993; 167:66.
  48. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999; 341:556.
  49. Urbanus AT, van de Laar TJ, Stolte IG, et al. Hepatitis C virus infections among HIV-infected men who have sex with men: an expanding epidemic. AIDS 2009; 23:F1.
  50. Wandeler G, Gsponer T, Bregenzer A, et al. Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic. Clin Infect Dis 2012; 55:1408.
  51. Luetkemeyer A, Hare CB, Stansell J, et al. Clinical presentation and course of acute hepatitis C infection in HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:31.
  52. van de Laar TJ, van der Bij AK, Prins M, et al. Increase in HCV incidence among men who have sex with men in Amsterdam most likely caused by sexual transmission. J Infect Dis 2007; 196:230.
  53. Rauch A, Rickenbach M, Weber R, et al. Unsafe sex and increased incidence of hepatitis C virus infection among HIV-infected men who have sex with men: the Swiss HIV Cohort Study. Clin Infect Dis 2005; 41:395.
  54. Fierer DS, Uriel AJ, Carriero DC, et al. Liver fibrosis during an outbreak of acute hepatitis C virus infection in HIV-infected men: a prospective cohort study. J Infect Dis 2008; 198:683.
  55. Centers for Disease Control and Prevention (CDC). Sexual transmission of hepatitis C virus among HIV-infected men who have sex with men--New York City, 2005-2010. MMWR Morb Mortal Wkly Rep 2011; 60:945.
  56. Serpaggi J, Chaix ML, Batisse D, et al. Sexually transmitted acute infection with a clustered genotype 4 hepatitis C virus in HIV-1-infected men and inefficacy of early antiviral therapy. AIDS 2006; 20:233.
  57. Danta M, Brown D, Bhagani S, et al. Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS 2007; 21:983.
  58. Götz HM, van Doornum G, Niesters HG, et al. A cluster of acute hepatitis C virus infection among men who have sex with men--results from contact tracing and public health implications. AIDS 2005; 19:969.
  59. Vanhommerig J, Lambers F, Schinkel J, et al. Risk Factors for Sexual Transmission of Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: A Case-Control Study. Open Forum Infect Dis 2015; 2:ofv115.
  60. Witt MD, Seaberg EC, Darilay A, et al. Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011. Clin Infect Dis 2013; 57:77.
  61. Polis CB, Shah SN, Johnson KE, Gupta A. Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. Clin Infect Dis 2007; 44:1123.
  62. Ridzon R, Gallagher K, Ciesielski C, et al. Simultaneous transmission of human immunodeficiency virus and hepatitis C virus from a needle-stick injury. N Engl J Med 1997; 336:919.
  63. Yonkers NL, Rodriguez B, Post AB, et al. HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells. J Infect Dis 2006; 194:391.
  64. Kim AY, Lauer GM, Ouchi K, et al. The magnitude and breadth of hepatitis C virus-specific CD8+ T cells depend on absolute CD4+ T-cell count in individuals coinfected with HIV-1. Blood 2005; 105:1170.
  65. Rohrbach J, Robinson N, Harcourt G, et al. Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy. Gut 2010; 59:1252.
  66. Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12:1365.
  67. Balagopal A, Philp FH, Astemborski J, et al. Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology 2008; 135:226.
  68. Balagopal A, Ray SC, De Oca RM, et al. Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution. AIDS 2009; 23:2397.
  69. Allison RD, Katsounas A, Koziol DE, et al. Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV. J Infect Dis 2009; 200:619.
  70. Volkmann X, Fischer U, Bahr MJ, et al. Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver. Hepatology 2007; 46:1498.
  71. Babu CK, Suwansrinon K, Bren GD, et al. HIV induces TRAIL sensitivity in hepatocytes. PLoS One 2009; 4:e4623.
  72. 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; 32:492.
  73. 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.
  74. 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/lvguidelines/adult_oi.pdf (Accessed on April 20, 2015).
  75. Berenguer J, Rodríguez E, Miralles P, et al. Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and Hepatitis C virus. Clin Infect Dis 2012; 55:728.
  76. Danta M, Semmo N, Fabris P, et al. Impact of HIV on host-virus interactions during early hepatitis C virus infection. J Infect Dis 2008; 197:1558.
  77. Kim AY, Schulze zur Wiesch J, Kuntzen T, et al. Impaired hepatitis C virus-specific T cell responses and recurrent hepatitis C virus in HIV coinfection. PLoS Med 2006; 3:e492.
  78. Thomson EC, Fleming VM, Main J, et al. Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men. Gut 2011; 60:837.
  79. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999; 30:1054.
  80. Monga HK, Rodriguez-Barradas MC, Breaux K, et al. Hepatitis C virus infection-related morbidity and mortality among patients with human immunodeficiency virus infection. Clin Infect Dis 2001; 33:240.
  81. Kirk GD, Mehta SH, Astemborski J, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study. Ann Intern Med 2013; 158:658.
  82. Fierer DS, Dieterich DT, Fiel MI, et al. Rapid progression to decompensated cirrhosis, liver transplant, and death in HIV-infected men after primary hepatitis C virus infection. Clin Infect Dis 2013; 56:1038.
  83. Konerman MA, Mehta SH, Sutcliffe CG, et al. Fibrosis progression in human immunodeficiency virus/hepatitis C virus coinfected adults: prospective analysis of 435 liver biopsy pairs. Hepatology 2014; 59:767.
  84. Sulkowski MS, Mehta SH, Torbenson MS, et al. Rapid fibrosis progression among HIV/hepatitis C virus-co-infected adults. AIDS 2007; 21:2209.
  85. Macías J, Berenguer J, Japón MA, et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with human immunodeficiency virus/hepatitis C virus. Hepatology 2009; 50:1056.
  86. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis 2001; 33:562.
  87. Sterling RK, Contos MJ, Sanyal AJ, et al. The clinical spectrum of hepatitis C virus in HIV coinfection. J Acquir Immune Defic Syndr 2003; 32:30.
  88. Martinez-Sierra C, Arizcorreta A, Díaz F, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. Clin Infect Dis 2003; 36:491.
  89. McGovern BH, Ditelberg JS, Taylor LE, et al. Hepatic steatosis is associated with fibrosis, nucleoside analogue use, and hepatitis C virus genotype 3 infection in HIV-seropositive patients. Clin Infect Dis 2006; 43:365.
  90. Gaslightwala I, Bini EJ. Impact of human immunodeficiency virus infection on the prevalence and severity of steatosis in patients with chronic hepatitis C virus infection. J Hepatol 2006; 44:1026.
  91. Sterling RK, Contos MJ, Smith PG, et al. Steatohepatitis: Risk factors and impact on disease severity in human immunodeficiency virus/hepatitis C virus coinfection. Hepatology 2008; 47:1118.
  92. Macías J, Berenguer J, Japón MA, et al. Hepatic steatosis and steatohepatitis in human immunodeficiency virus/hepatitis C virus-coinfected patients. Hepatology 2012; 56:1261.
  93. Limketkai BN, Mehta SH, Sutcliffe CG, et al. Relationship of liver disease stage and antiviral therapy with liver-related events and death in adults coinfected with HIV/HCV. JAMA 2012; 308:370.
  94. Macías J, Márquez M, Téllez F, et al. Risk of liver decompensation among HIV/hepatitis C virus-coinfected individuals with advanced fibrosis: implications for the timing of therapy. Clin Infect Dis 2013; 57:1401.
  95. Silver D, Karnik G, Osinusi A, et al. Effect of HIV on liver fibrosis among HCV-infected African Americans. Clin Infect Dis 2013; 56:1280.
  96. Salmon-Ceron D, Rosenthal E, Lewden C, et al. Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité 2005 study. J Hepatol 2009; 50:736.
  97. Merchante N, Merino E, López-Aldeguer J, et al. Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain. Clin Infect Dis 2013; 56:143.
  98. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med 2008; 148:728.
  99. Puoti M, Bruno R, Soriano V, et al. Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS 2004; 18:2285.
  100. Kramer JR, Kowalkowski MA, Duan Z, Chiao EY. The effect of HIV viral control on the incidence of hepatocellular carcinoma in veterans with hepatitis C and HIV coinfection. J Acquir Immune Defic Syndr 2015; 68:456.
  101. Bräu N, Fox RK, Xiao P, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study. J Hepatol 2007; 47:527.
  102. Lo Re V 3rd, Kallan MJ, Tate JP, et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study. Ann Intern Med 2014; 160:369.
  103. Anderson JP, Tchetgen Tchetgen EJ, Lo Re V 3rd, et al. Antiretroviral therapy reduces the rate of hepatic decompensation among HIV- and hepatitis C virus-coinfected veterans. Clin Infect Dis 2014; 58:719.
  104. Pineda JA, García-García JA, Aguilar-Guisado M, et al. Clinical progression of hepatitis C virus-related chronic liver disease in human immunodeficiency virus-infected patients undergoing highly active antiretroviral therapy. Hepatology 2007; 46:622.
  105. Pineda JA, Aguilar-Guisado M, Rivero A, et al. Natural history of compensated hepatitis C virus-related cirrhosis in HIV-infected patients. Clin Infect Dis 2009; 49:1274.
  106. Lo Re V 3rd, Wang L, Devine S, et al. Hepatic decompensation in patients with HIV/Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) triple infection versus HIV/HCV coinfection and the effect of anti-HBV nucleos(t)ide therapy. Clin Infect Dis 2014; 59:1027.
  107. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 2007; 146:87.
  108. Chen TY, Ding EL, Seage Iii GR, Kim AY. Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression. Clin Infect Dis 2009; 49:1605.
  109. Merchante N, Girón-González JA, González-Serrano M, et al. Survival and prognostic factors of HIV-infected patients with HCV-related end-stage liver disease. AIDS 2006; 20:49.
  110. Bräu N, Salvatore M, Ríos-Bedoya CF, et al. Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy. J Hepatol 2006; 44:47.
  111. Thein HH, Yi Q, Dore GJ, Krahn MD. Natural history of hepatitis C virus infection in HIV-infected individuals and the impact of HIV in the era of highly active antiretroviral therapy: a meta-analysis. AIDS 2008; 22:1979.
  112. Anderson KB, Guest JL, Rimland D. Hepatitis C virus coinfection increases mortality in HIV-infected patients in the highly active antiretroviral therapy era: data from the HIV Atlanta VA Cohort Study. Clin Infect Dis 2004; 39:1507.
  113. 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; 356:1800.
  114. Pascual-Pareja JF, Caminoa A, Larrauri C, et al. HAART is associated with lower hepatic necroinflammatory activity in HIV-hepatitis C virus-coinfected patients with CD4 cell count of more than 350 cells/microl at the time of liver biopsy. AIDS 2009; 23:971.
  115. Thorpe J, Saeed S, Moodie EE, et al. Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection. AIDS 2011; 25:967.
  116. Shafran SD. Early initiation of antiretroviral therapy: the current best way to reduce liver-related deaths in HIV/hepatitis C virus-coinfected patients. J Acquir Immune Defic Syndr 2007; 44:551.
  117. Berenguer J, Bellón JM, Miralles P, et al. Association between exposure to nevirapine and reduced liver fibrosis progression in patients with HIV and hepatitis C virus coinfection. Clin Infect Dis 2008; 46:137.
  118. Macías J, Castellano V, Merchante N, et al. Effect of antiretroviral drugs on liver fibrosis in HIV-infected patients with chronic hepatitis C: harmful impact of nevirapine. AIDS 2004; 18:767.
  119. Yoo TW, Donfield S, Lail A, et al. Effect of hepatitis C virus (HCV) genotype on HCV and HIV-1 disease. J Infect Dis 2005; 191:4.
  120. Daar ES, Lynn H, Donfield S, et al. Hepatitis C virus load is associated with human immunodeficiency virus type 1 disease progression in hemophiliacs. J Infect Dis 2001; 183:589.
  121. Tedaldi EM, Baker RK, Moorman AC, et al. Influence of coinfection with hepatitis C virus on morbidity and mortality due to human immunodeficiency virus infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2003; 36:363.
  122. Hernando V, Perez-Cachafeiro S, Lewden C, et al. All-cause and liver-related mortality in HIV positive subjects compared to the general population: differences by HCV co-infection. J Hepatol 2012; 57:743.
  123. Sulkowski MS, Moore RD, Mehta SH, et al. Hepatitis C and progression of HIV disease. JAMA 2002; 288:199.
  124. Rockstroh JK, Mocroft A, Soriano V, et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis 2005; 192:992.
  125. Piroth L. Coinfection with hepatitis C virus and HIV: more than double trouble. Clin Infect Dis 2009; 49:623.
  126. van der Helm J, Geskus R, Sabin C, et al. Effect of HCV infection on cause-specific mortality after HIV seroconversion, before and after 1997. Gastroenterology 2013; 144:751.
  127. Sherman KE, O'Brien J, Gutierrez AG, et al. Quantitative evaluation of hepatitis C virus RNA in patients with concurrent human immunodeficiency virus infections. J Clin Microbiol 1993; 31:2679.
  128. Dorrucci M, Pezzotti P, Phillips AN, et al. Coinfection of hepatitis C virus with human immunodeficiency virus and progression to AIDS. Italian Seroconversion Study. J Infect Dis 1995; 172:1503.
  129. Kovacs A, Karim R, Mack WJ, et al. Activation of CD8 T cells predicts progression of HIV infection in women coinfected with hepatitis C virus. J Infect Dis 2010; 201:823.
  130. Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999; 179:859.
  131. Potter M, Odueyungbo A, Yang H, et al. Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy. AIDS 2010; 24:1857.
  132. Hull MW, Rollet K, Odueyungbo A, et al. Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis 2012; 54:1798.
  133. Claassen CW, Diener-West M, Mehta SH, et al. Discordance between CD4+ T-lymphocyte counts and percentages in HIV-infected persons with liver fibrosis. Clin Infect Dis 2012; 54:1806.
  134. Dong HV, Cortés YI, Shiau S, Yin MT. Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS 2014; 28:2119.
  135. O'Neill TJ, Rivera L, Struchkov V, et al. The effect of HIV-hepatitis C co-infection on bone mineral density and fracture: a meta-analysis. PLoS One 2014; 9:e101493.
  136. Lucas GM, Jing Y, Sulkowski M, et al. Hepatitis C viremia and the risk of chronic kidney disease in HIV-infected individuals. J Infect Dis 2013; 208:1240.
  137. Kakinami L, Block RC, Adams MJ, et al. Risk of cardiovascular disease in HIV, hepatitis C, or HIV/hepatitis C patients compared to the general population. Int J Clin Pract 2013; 67:6.
  138. Sosner P, Wangermez M, Chagneau-Derrode C, et al. Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus co-infection. Atherosclerosis 2012; 222:274.
  139. Masiá M, Padilla S, Robledano C, et al. Evaluation of endothelial function and subclinical atherosclerosis in association with hepatitis C virus in HIV-infected patients: a cross-sectional study. BMC Infect Dis 2011; 11:265.
  140. Freiberg MS, Chang CC, Skanderson M, et al. The risk of incident coronary heart disease among veterans with and without HIV and hepatitis C. Circ Cardiovasc Qual Outcomes 2011; 4:425.
  141. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group, Weber R, Sabin C, et al. HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study. Antivir Ther 2010; 15:1077.
  142. Strader DB, Wright T, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004; 39:1147.
  143. Bani-Sadr F, Barange K, Daoud F, et al. Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis. HIV Med 2009; 10:417.
  144. Bonacini M, Lin HJ, Hollinger FB. Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquir Immune Defic Syndr 2001; 26:340.
  145. Thio CL, Nolt KR, Astemborski J, et al. Screening for hepatitis C virus in human immunodeficiency virus-infected individuals. J Clin Microbiol 2000; 38:575.
  146. Chamie G, Bonacini M, Bangsberg DR, et al. Factors associated with seronegative chronic hepatitis C virus infection in HIV infection. Clin Infect Dis 2007; 44:577.
  147. Mehta SH, Cox A, Hoover DR, et al. Protection against persistence of hepatitis C. Lancet 2002; 359:1478.
  148. http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/ucm217553.htm (Accessed on October 17, 2011).
  149. Smith BD, Drobeniuc J, Jewett A, et al. Evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus. J Infect Dis 2011; 204:825.
  150. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
  151. Thomson EC, Nastouli E, Main J, et al. Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV. AIDS 2009; 23:89.
  152. Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014; 58:1.
  153. Linas BP, Wong AY, Schackman BR, et al. Cost-effective screening for acute hepatitis C virus infection in HIV-infected men who have sex with men. Clin Infect Dis 2012; 55:279.
  154. Laurence JC. Hepatitis A and B immunizations of individuals infected with human immunodeficiency virus. Am J Med 2005; 118 Suppl 10A:75S.
  155. Nelson M, Matthews G, Brook MG, et al. BHIVA guidelines on HIV and chronic hepatitis: coinfection with HIV and hepatitis C virus infection (2005). HIV Med 2005; 6 Suppl 2:96.
  156. Alberti A, Clumeck N, Collins S, et al. Short statement of the first European Consensus Conference on the treatment of chronic hepatitis B and C in HIV co-infected patients. J Hepatol 2005; 42:615.
  157. Bonfanti P, Valsecchi L, Parazzini F, et al. Incidence of adverse reactions in HIV patients treated with protease inhibitors: a cohort study. Coordinamento Italiano Studio Allergia e Infezione da HIV (CISAI) Group. J Acquir Immune Defic Syndr 2000; 23:236.
  158. Cooper CL, Parbhakar MA, Angel JB. Hepatotoxicity associated with antiretroviral therapy containing dual versus single protease inhibitors in individuals coinfected with hepatitis C virus and human immunodeficiency virus. Clin Infect Dis 2002; 34:1259.
  159. 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; 14:2895.
  160. Núñez M, Lana R, Mendoza JL, et al. Risk factors for severe hepatic injury after introduction of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001; 27:426.
  161. Reisler R, Burman W, et al. Incidence of grade IV events, AIDS, and mortality in a large multicenter cohort receiving HAART, Abstract #36. In: 9th Conference on Retroviruses and Opportunistic Infections, Foundation for Retrovirology and Human Health, Seattle, WA 2002.
  162. Vento S, Garofano T, Renzini C, et al. Enhancement of hepatitis C virus replication and liver damage in HIV-coinfected patients on antiretroviral combination therapy. AIDS 1998; 12:116.
  163. Puoti M, Torti C, Ripamonti D, et al. Severe hepatotoxicity during combination antiretroviral treatment: incidence, liver histology, and outcome. J Acquir Immune Defic Syndr 2003; 32:259.
  164. French AL, Benning L, Anastos K, et al. Longitudinal effect of antiretroviral therapy on markers of hepatic toxicity: impact of hepatitis C coinfection. Clin Infect Dis 2004; 39:402.
  165. Savès 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 dEpidémiologie Clinique de Sida en Aquitaine (GECSA). AIDS 1999; 13:F115.
  166. Servoss JC, Kitch DW, Andersen JW, et al. Predictors of antiretroviral-related hepatotoxicity in the adult AIDS Clinical Trial Group (1989-1999). J Acquir Immune Defic Syndr 2006; 43:320.
  167. Mariné-Barjoan E, Saint-Paul MC, Pradier C, et al. Impact of antiretroviral treatment on progression of hepatic fibrosis in HIV/hepatitis C virus co-infected patients. AIDS 2004; 18:2163.
  168. John M, Flexman J, French MA. Hepatitis C virus-associated hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease? AIDS 1998; 12:2289.
  169. Vispo E, Fernández-Montero JV, Labarga P, et al. Low risk of liver toxicity using the most recently approved antiretroviral agents but still increased in HIV-hepatitis C virus coinfected patients. AIDS 2013; 27:1187.