Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

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Abstract

Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were measured. No significant difference in LPS, EndoCAb, Cyt-c levels between HIV and HIV/HCV patients was found. The CK18 level was higher in the HIV/HCV group. Correlation between CD4+ cell count and EndoCAb antibodies was found in HCV positive patients. There was a significant effect of ART on markers for EndoCAb IgA and EndoCAb IgM antibodies in the HIV monoinfected group. Correlation between CD4+ cell count and EndoCAb antibodies and LPS was found in HIV/HCV patients on ART. Coinfection with HCV can lead to more pronounced response in EndoCAb antibody production and higher levels of cell apoptosis markers, despite similar LPS levels. ART has a positive effect on immune activation.

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  • Abad-Fernandez M. Vallejo A. Hernandez-Novoa B. Diaz L. Gutierrez C. Madrid N. Angeles Munoz M. Moreno S. (2013). Correlation between different methods to measure microbial translocation and its association with immune activation in long-term supressed HIV-1 infected individuals. J. Acquir. Immune Defic. Syndr.64 149–153.

  • Albillos A. de la Hera A. Gonzalez M. Moya J.-L. Calleja J.-L. Monserrat J. Riuz-del-Arbol L. Alvarez-Mon M. (2003). Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology37 (1) 208–217.

  • Balagopal A. Phil F. H. Astemborski J. Block T. M. Mehta A. Long R. Kirk G. D. Mehta S. H. Cox A. L. Thomas D. L. Ray S. C. (2008). Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology135 (1) 226–233.

  • Balagopal A. Gama L. Franco V. Russell J. N. Quinn J. Higgins Y. Smeaton L. M. Clements J. E. Thomas D. L. Gupta A. (2012). Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma. PLoS ONE7 (8) 1–8.

  • Brenchley J. M. Price D. A. Schacker T. W. Asher T. E. Silvestri G. Rao S. Kazzaz Z. Bornstein E. Lambotte O. Altmann D. Blazar B. R. Rodriguez B. Teixeira-Johnson L. Landay A. Martin J. N. Hecht F. M. Picker L. J. Lederman M. M. Deeks S. G. Douek D. C. (2006). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature Med.12 1365–1371.

  • Caradonna L. Mastronardi M. L. Magrone T. Cozzolongo R. Cuppone R. Manghisi O. G. Caccavo D. Pellegrino N. M. Amoroso A. Jirillo E. Amati L. (2002). Biological and clinical significance of entotoxemia in the course of hepatitis C virus infection. Curr. Pharmaceut. Des.8 995–1005.

  • Chan C. C. Hwang S. J. Lee F. Y. Wang S. S. Chang F. Y. Li C. P. Chu C. J. Lu R. H. Lee S. D. (1997). Prognostic value of plasma endotoxin levels in patients with cirrhosis. Scand. J. Gastroenterol.32 (9) 942–945.

  • Crane M. Iser D. Lewin S. R. (2012). Human immunodeficiency virus infection and the liver. World J. Hepatol.4 (3) 91–98.

  • Dinh D. M. Volpe G. E. Duffalo C. Bhalchandra S. Tai A. K. Kane A. V. Wanke C. A. Ward H. D. (2015). Intestinal microbiota microbial translocation and systemic inflammation in chronic HIV infection. J. Infect. Dis.211 19–27.

  • Epeldegui M. Magpantay L. Guo Y. Halec G. Cumberland W. G. Yen P. K. Macatangay B. Margolick J. B. Fositch A. F. Wolinsky S. Martinez-Maza O. Hussain S. K. (2018). A prospective study of serum microbial translocation biomarkers and risk of AIDS- related non- Hodgkin lymphoma. AIDS32 (7) 945–954.

  • Epple H.-J. Schneider T. Troeger H. Kunkel D. Allers K. Moos V. Amasheh M. Loddenkemper C. Fromm M. Zeitz M. Schulzke J.-D. (2009). Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV- infected patients. Gut58 220–227.

  • French A. Evans C. T. Agniel D. M. Cohen M. H. Peters M. Landay A. L. Desai S. N. (2013). Microbial translocation and liver disease progression in women coinfected with HIV and hepatitis C virus. J. Infect. Dis.208 679–689.

  • Hansjee N. Kaufmann G. R. Strub C. Weber R. Battegay M. Erb P. (2004). Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes. J. Acquir. Immune Defic. Syndr.36 671–677.

  • Hatano H. (2013). Immune activation and HIV persistence: Considerations for novel therapeutic interventions. AIDS8 (3) 211–216.

  • Jiang W. Lederman M. M. Hunt P. Sieg S. F. Haley K. Rodriguez B. Landay A. Martin J. Sinclair E. Asher A. I. Deeks S. G. Douek D. C. Brenchley J. M. (2009). Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J. Infect. Dis.199 (8) 1177–1185.

  • Jirillo E. Amati L. Caradonna L. Greco B. Cozzolongo R. Cuppone R. Piazzolla G. Caccavo D. Antonaci S. Manghisi O. G. (1998). Soluble (s) CD14 and plasmatic lipopolysaccharides (LPS) in patients with chronic hepatitis C before and after treatment with interferon (IFN)-α. Immunopharmacol. Immunotoxicol.20 (1) 1–14.

  • Kronenberger B. von Wagner M. Herrmann E. Mihm U. Piiper A. Sarrazin C. Zeuzem S. (2005). Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J. Viral Hepat. 12 307–314.

  • Lopez-Cortes L. F. Trujillo-Rodriguez M. Baez-Palomo A. Benmarzouk-Hidalgo O. J. Dominguez-Molina B. Milanes-Guisado Y. Espinosa N. Viciana P. Gutierrez-Valencia A. (2018). Eradication of hepatitis C virus (HCV) reduces immune activation microbial trans-location and the HIV DNA level in HIV/HCV-coinfected patients. J. Infect. Dis.218 (4) 624–632.

  • Macias J. Japon M. A. Saez C. Palacios R. B. Mira J. A. Garcia-Garcia J. A. Merchante N. Vergara S. Lozano F. Gomez-Mateos J. Pineda J. A. (2005). Increased hepatocyte Fas expression and apoptosis in HIV and hepatitis C virus infection. J. Infect. Dis.192 1566–1576.

  • Marchetti G. Bellistri G. M. Borghi E. Tincati C. Ferramosca S. La Francesca M. Morace G. Gori A. d`Arminio Monforte A. (2008). Microbial translocation is associated with sustained failure in CD+ T-cell reconstitution in HIV-infected patients on long-term highly active anti-retroviral therapy. AIDS22 2035–2044.

  • Marchetti G. Cozzi-Lepri A. Merlini E. Bellistri G. M. Castagna A. Galli M. Verrucchi G. Antinori A. Costantini A. Giacometti A. di Caro A. D’arminio Monforte A. (2011). Microbial translocation predicts disease progression of HIV- infected antiretroviral- naïve patients with high CD4+ cell count. AIDS25 1385–1394.

  • Marchetti G. Tincati C. Silvestri G. (2013). Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin. Microbiol. Rev.26 2–18.

  • Marquez M. Romero-Cores P. Montes-Oca M. Martin-Aspas A. Soto-Cardenas M.-J. Guerrero F. Fernandez-Gutierrez C. Giron-Gonzalez J.-A. (2015). Immune activation response in chronic HIV-infected patients: Influence of hepatitis C virus coinfection. PLoS ONE10 (3) 1–15.

  • Marks M. A. Rabkin C. S. Engels E. A. Busch E. Kopp W. Rager H. Goedert J. J. Chaturvedi A. K. (2012). Markers of microbial translocation and risk of AIDS-related lymphoma. AIDS27 469–474.

  • Mhawej M.-J. Brunet-Francois C. Fonteneau R. Ernst D. Ferre V. Stan G.-B. Raffi F. Moog C. H. (2009). Apoptosis characterizes immunological failure of HIV infected patients. Control Eng. Practice17 798–804.

  • Nien H.-C. Hsu S.-J. Su T.-H. Yang P.-J. Sheu J.-C. Wang J.-T. Chow L.-P. Chen C.-L. Kao J.-H. Yang W.-S. (2017). High serum lipopolysaccharide-binding protein level in chronic hepatitis C viral infection is reduced by anti-viral treatments. PLoS ONE12 (1) 1–11.

  • Novati S. Sacchi P. Cima S. Zuccaro V. Columpsi P. Pagani L. Filice G. Bruno R. (2015). General issues on microbial translocation in HIV-infected patients. Eur. Rev. Med. Pharmacol. Sci19 866–878.

  • de Oliveira Pinto L. M. Lecoeur H. Ledru E. Rapp C. Patey O. Gougeon M.-L. (2002). Lack of control of T cell apoptosis under HAART. Influence of therapy regimen in vivo and in vitro. AIDS16 329–339.

  • Parfieniuk-Kowerda A. Lapinski T. W. Rogalska-Plonska M. Swiderska M. Panasiuk A. Jaroszewicz J. Flisika R. (2013). Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C. Liver Int.34 544–550.

  • Roger P.-M. Breittmayer J.-P. Durant J. Sanderson F. Ceppi C. Brignone C. Cua E. Clevenbergh P. Fuzibet J.-G. Pesce A. Bernard A. Dellamonica P. (2002). Early CD4+ T cell recovery in human immunodeficiency virus-infected patients receiving effective therapy is related to a down-regulation of apoptosis and not to proliferation. J. Infect. Dis. 185 463–470.

  • Rohrbach J. Stickel F. Schmid P. Thormann W. Kovari H. Scherrer A. Gunthard H. F. Vuichard D. Cavassini M. Ambrosioni J. Bernasconi E. Furrer H. Rauch A. (2013). Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals. Antiviral Ther.19 149–159.

  • Sandler N. G. Wand H. Roque A. Law M. Nason M. C. Nixon D. E. Pedersen C. Ruxrungtham K. Lewin S. R. Emery S. Neaton J. D. Brenchley J. M. Deeks S. G. Sereti I. Douek D. C. (2011). Plasma levels of soluble CD14 independently predict mortality in HIV patients. J. Infect. Dis. 203 780–790.

  • Sandler N. G. Douek D. C. (2012). Microbial translocation in HIV infection: Causes consequences and treatment opportunities. Nature Rev. Microbiol.10 655–666.

  • Seidel N. Volkmann X. Langer F. Flemming P. Manns M. P. Schulze-Osthoff K. Bantel H. (2005). The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum. Hepatology42 113–120.

  • Vassallo M. Mercie P. Cottalorda J. Ticchioni M. Dellamonica P. (2012). The role of lipopolysaccharide as a marker of immune activation in HIV-1 infected patients: A systematic literature review. Virology J.9 (174) 1–8.

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