Mortality in hepatitis C virus-infected patients with a diagnosis of AIDS in the era of combination antiretroviral therapy

Andrea D Branch, Mark L Van Natta, Marie-Louise Vachon, Douglas T Dieterich, Curtis L Meinert, Douglas A Jabs, Studies of the Ocular Complications of AIDS Research Group, Andrea D Branch, Mark L Van Natta, Marie-Louise Vachon, Douglas T Dieterich, Curtis L Meinert, Douglas A Jabs, Studies of the Ocular Complications of AIDS Research Group

Abstract

Background: Before the introduction of combination antiretroviral therapy (cART), patients infected with the human immunodeficiency virus (HIV) rarely died of liver disease. In resource-rich countries, cART dramatically increased longevity. As patients survived longer, hepatitis C virus (HCV) infection became a leading cause of death; however, because patients with AIDS continue to have 5-fold greater mortality than non-AIDS patients, it is unclear whether HCV infection increases mortality in them.

Methods: In this investigation, which is part of the Longitudinal Studies of the Ocular Complications of AIDS, plasma banked at enrollment from 2025 patients with AIDS as defined by the Centers for Disease Control and Prevention were tested for HCV RNA and antibodies.

Results: Three hundred thirty-seven patients had HCV RNA (chronic infection), 91 had HCV antibodies and no HCV RNA (cleared infection), and 1597 had no HCV markers. Median CD4(+) T-cell counts/µL were 200 (chronic), 193 (cleared), and 175 (no markers). There were 558 deaths. At a median follow-up of 6.1 years, patients with chronic HCV had a 50% increased risk of mortality compared with patients with no HCV markers (relative risk [RR], 1.5; 95% confidence interval [CI], 1.2-1.9; P = .001) in an adjusted model that included known risk factors. Mortality was not increased in patients with cleared infection (RR, 0.9; 95% CI, .6-1.5; P = .82). In patients with chronic HCV, 20.4% of deaths were liver related compared with 3.8% in patients without HCV.

Conclusions: Chronic HCV infection is independently associated with a 50% increase in mortality among patients with a diagnosis of AIDS, despite competing risks. Effective HCV treatment may benefit HIV/HCV-coinfected patients with AIDS.

Figures

Figure 1.
Figure 1.
Kaplan-Meier survival curves indicate that chronic hepatitis C virus infection was associated with an increased mortality risk. Abbreviation: HCV, hepatitis C virus.

References

    1. Greub G, Ledergerber B, Battegay M, et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and HCV coinfection: the Swiss HIV cohort study. Lancet. 2000;356:1800–5.
    1. Bica I, McGovern B, Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with HIV infection. Clin Infect Dis. 2001;32:492–7.
    1. Lewden C, Salmon D, Morlat P, et al. Causes of death among HIV-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS. Int J Epidemiol. 2005;34:121–30.
    1. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA. 2008;300:51–9.
    1. Smith C, Sabin CA, et al. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D study. AIDS. 2010;24:1537–48.
    1. 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;166:1632–41.
    1. Rosenthal E, Pialoux G, Bernard N, et al. Liver-related mortality in human-immunodeficiency-virus-infected patients between 1995 and 2003 in the French GERMIVIC Joint Study Group Network (MORTAVIC 2003 study) J Viral Hepat. 2007;14:183–8.
    1. 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;34:831–7.
    1. 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;49:1605–15.
    1. Omland LH, Jepsen P, Weis N, et al. Mortality in HIV-infected injection drug users with active vs cleared hepatitis C virus-infection: a population-based cohort study. J Viral Hepat. 2010;17:261–8.
    1. Centers for Disease Control and Prevention. Basic statistics. Available at: . Accessed 2 November 2011.
    1. Jabs DA, Holbrook JT, Van Natta ML, et al. Risk factors for mortality in patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmol. 2005;112:771–9.
    1. Castro KG, Ward JW, Slutsker L, et al. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Clin Infect Dis. 1993;17:802–10.
    1. Jabs DA, Van Natta ML, Holbrook JT, et al. Longitudinal study of the ocular complications of AIDS: 1. Ocular diagnoses at enrollment. Ophthalmol. 2007;114:780–6.
    1. Jabs DA, Bolton SG, Dunn JP, Palestine AG. Discontinuing anticytomegalovirus therapy in patients with immune reconstitution after combination antiretroviral therapy. Am J Ophthalmol. 1998;126:817–22.
    1. SAS Institute Inc. SAS/STAT User's Guide (Version 8) Cary, NC: SAS Institute Inc; 1999.
    1. Stata Data Analysis and Statistical Software [Software] College Station, TX: StataCorp LP; 2001.
    1. Shores NJ, Maida I, Soriano V, Núñez M. Sexual transmission is associated with spontaneous HCV clearance in HIV-infected patients. J Hepatol. 2008;49:323–8.
    1. Melendez-Morales L, Konkle BA, Preiss L, et al. Chronic hepatitis B and other correlates of spontaneous clearance of hepatitis C virus among HIV-infected people with hemophilia. AIDS. 2007;21:1631–6.
    1. 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;351:438–50.
    1. 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;292:2839–48.
    1. 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;23:972–82.
    1. 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;50:407–13.
    1. 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;196:670–6.
    1. Antonucci G, Girardi E, Cozzi-Lepri A, et al. Role of hepatitis C virus (HCV) viremia and HCV genotype in the immune recovery from highly active antiretroviral therapy in a cohort of antiretroviral-naive HIV-infected individuals. Clin Infect Dis. 2005;40:e101–9.
    1. Potter M, Odueyungbo A, Yang H, Saeed S, Klein MB Canadian Co-infection Cohort Study Investigators. Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy. AIDS. 2010;24:1857–65.
    1. Backus LI, Boothroyd D, Deyton LR. HIV, hepatitis C and HIV/hepatitis C virus co-infection in vulnerable populations. AIDS. 2005;19:S13–9.
    1. Backus LI, Phillips BR, Boothroyd DB, et al. Effects of hepatitis C virus coinfection on survival in veterans with HIV treated with highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2005;39:613–9.
    1. Dolganiuc A, Chang S, Kodys K, et al. Hepatitis C virus (HCV) core protein-induced, monocyte-mediated mechanisms of reduced IFN-alpha and plasmacytoid dendritic cell loss in chronic HCV infection. J Immunol. 2006;177:6758–68.
    1. Lucas M, Vargas-Cuero AL, Lauer GM, et al. Pervasive influence of hepatitis C virus on the phenotype of antiviral CD8+ T cells. J Immunol. 2004;172:1744–53.
    1. Campbell JV, Hagan H, Latka MH, et al. High prevalence of alcohol use among hepatitis C virus antibody positive injection drug users in three US cities. Drug Alcohol Depend. 2006;81:259–65.
    1. Larsen MV, Omland LH, Gerstoft J, et al. Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study. Addiction. 2010;105:529–35.
    1. Cohen MH, Grey D, Cook JA, et al. Awareness of hepatitis C infection among women with and at risk for HIV. J Gen Intern Med. 2007;22:1689–94.
    1. Volk ML, Tocco R, Saini S, Lok AS. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50:1750–55.
    1. Masur H, Kaplan JE, Holmes KK US Public Health Service; Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons–2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. Ann Intern Med. 2002;137:435–78.
    1. George SL, Gebhardt J, Klinzman D, et al. Hepatitis C virus viremia in HIV-infected individuals with negative HCV antibody tests. J Acquir Immune Defic Syndr. 2002;31:154–62.
    1. Axelrod DA, Gheorghian A, Schnitzler MA, et al. The economic implications of broader sharing of liver allografts. Am J Transplant. 2011;11:798–807.

Source: PubMed

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