Abstract
Hepatitis C virus (HCV) is a common opportunistic pathogen especially among Human immunodeficiency virus (HIV) infected patients. Due to incongruous studies, the pathological effect of HCV on HIV induced disease are still not fully understood. While some studies have showed no effect of HCV on HIV infection, others reported a defined role of HCV in aggravating the rates of AIDS-related illnesses and mortality. The explanation of such variances may be due to the host immune response, viral genotypes, sub-type and quasi-species distribution. The factors that complicate the management of HIV/HCV patients are: (1) reduced HCV antibody production, (2) drug interactions, (3) liver disease and (4) different epidemiologic characteristics. However, it is abundantly clear that the morbidity and mortality caused by HCV have increased since the introduction of highly active antiretroviral therapy (HAART) against HIV. In this review, the consequence of HIV/HCV co-infection on host immune response, viral replication, disease progression, mortality and morbidity, viral load, persistence and current treatment options have been discussed. Based on the clinical studies, it is necessary to evaluate the effect of HCV therapy on HIV progression and to provide a fully active HCV treatment for patients receiving HIV treatment. In conclusion, it is recommended to provide fully active HAART therapy in combination with a known HCV therapy.
Similar content being viewed by others
References
AIDSinfo. Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. 2016. http://www.aidsinfonihgov/guidelines.
Askarieh G, Alsiö A, Pugnale P, Negro F, Ferrari C, Neumann AU, et al. Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C. Hepatology. 2010;51(5):1523–30. https://doi.org/10.1002/hep.23509.
Blackard JT, Yang Y, Bordoni P, Sherman KE, Chung RT. Team ACTGS. Hepatitis C virus (HCV) diversity in HIV-HCV-coinfected subjects initiating highly active antiretroviral therapy. J Infect Dis. 2004;189(8):1472–81. https://doi.org/10.1086/382959.
Boesecke C, Rockstroh JK. Acute hepatitis C in patients with HIV. Semin Liver Dis. 2012;32(2):130–7. https://doi.org/10.1055/s-0032-1316468.
Branch AD, Van Natta ML, Vachon M-L, Dieterich DT, Meinert CL, Jabs DA, et al. Mortality in hepatitis C virus-infected patients with a diagnosis of AIDS in the era of combination antiretroviral therapy. Clin Infect Dis. 2012;55(1):137–44. https://doi.org/10.1093/cid/cis404.
Chary A, Winters MA, Kottilil S, Murphy AA, Polis MA, Holodniy M. Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease quasispecies diversity in HIV- and HCV-coinfected patients. J Infect Dis. 2010;202(6):889–93. https://doi.org/10.1086/655784.
Cho H, Kikuchi M, Li Y, Nakamoto N, Amorosa VK, Valiga ME, et al. Induction of multiple immune regulatory pathways with differential impact in HCV/HIV coinfection. Front Immunol. 2014. https://doi.org/10.3389/fimmu.2014.00265.
Cotte L, Braun J, Sogni P, Vincent C, Valantin M-A, Vittecoq D, Michelet C, Batisse D, Morlat P, Gervais A, Pawlotsky J-M, Aboulker J-P, Molina J-M. High end-of-treatment (EOT) response rate with telaprevir-PegIFN-RBV in treatment-experienced HIV coinfected patients with HCV genotype 1: ANRS HC26 TelapreVIH study. In: 64th Annual Meeting of the American Association for the Study of Liver Diseases. 2013.
De Lédinghen V, Barreiro P, Foucher J, Labarga P, Castéra L, Vispo ME, et al. Liver fibrosis on account of chronic hepatitis C is more severe in HIV-positive than HIV-negative patients despite antiretroviral therapy. J Viral Hepat. 2008;15(6):427–33. https://doi.org/10.1111/j.1365-2893.2007.00962.x.
Dieterich D, Rockstroh J, Orkin C, et al. Simeprevir (TMC435) plus peginterferon/ribavirin in patients co-infected with HCV genotype-1 and HIV-1: primary analysis of the C212 study. In: 14th European AIDs conference. 2013.
Dorward J, Garrett N, Scott D, Buckland M, Orkin C, Baily G. Successful treatment of acute hepatitis C virus in HIV positive patients using the European AIDS Treatment Network guidelines for treatment duration. J Clin Virol. 2011;52(4):367–9. https://doi.org/10.1016/j.jcv.2011.08.020.
EACS. European AIDS Clinical Society. Guidelines, Version 7.0. [online]. 2013. http://www.eacsocietyorg/Portals/0/Guidelines_Online.
Fierer DS, Dieterich DT, Mullen MP, Branch AD, Uriel AJ, Carriero DC, et al. Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men. Clin Infect Dis. 2014;58(6):873–9. https://doi.org/10.1093/cid/cit799.
García-Álvarez M, Berenguer J, Jiménez-Sousa MA, Pineda-Tenor D, Aldámiz-Echevarria T, Tejerina F, et al. Mx1, OAS1 and OAS2 polymorphisms are associated with the severity of liver disease in HIV/HCV-coinfected patients: a cross-sectional study. Sci Rep. 2017;7:41516. https://doi.org/10.1038/srep41516.
Global Health Observatory (GHO) data. http://www.who.int/gho/hiv/en/. Last accessed on 25.12.2017.
Gonzalez FA, Van den Eynde E, Perez-Hoyos S, Navarro J, Curran A, Burgos J, et al. Liver stiffness and aspartate aminotransferase levels predict the risk for liver fibrosis progression in hepatitis C virus/HIV-coinfected patients. HIV Med. 2015;16(4):211–8. https://doi.org/10.1111/hiv.12197.
Gupta P, Liu B, Wu JQ, Soriano V, Vispo E, Carroll AP, et al. Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection. Virology. 2014;450–451:336–49. https://doi.org/10.1016/j.virol.2013.12.026.
Jabara CB, Hu F, Mollan KR, Williford SE, Menezes P, Yang Y, et al. Hepatitis C Virus (HCV) NS3 sequence diversity and antiviral resistance-associated variant frequency in HCV/HIV coinfection. Antimicrob Agents Chemother. 2014;58(10):6079–92. https://doi.org/10.1128/aac.03466-14.
Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368(20):1867–77. https://doi.org/10.1056/NEJMoa1214854.
Kaczmarek DJ, Kokordelis P, Krämer B, Glässner A, Wolter F, Goeser F, et al. Alterations of the NK cell pool in HIV/HCV co-infection. PLoS ONE. 2017;12(4):e0174465. https://doi.org/10.1371/journal.pone.0174465.
Kim AY, Chung RT. Coinfection with HIV-1 and HCV—a one-two punch. Gastroenterology. 2009;137(3):795–814. https://doi.org/10.1053/j.gastro.2009.06.040.
Kong L, Welge JA, Powell EA, Blackard JT. HIV infection of hepatocytes results in a modest increase in hepatitis C virus expression in vitro. PLoS ONE. 2014;9(2):e83728. https://doi.org/10.1371/journal.pone.0083728.
Lacombe K, Rockstroh J. HIV and viral hepatitis coinfections: advances and challenges. Gut. 2012;61(Suppl 1):i47–58. https://doi.org/10.1136/gutjnl-2012-302062.
Lambers FAE, Prins M, Thomas X, Molenkamp R, Kwa D, Brinkman K, et al. Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM. AIDS. 2011;25(17):F21–7. https://doi.org/10.1097/QAD.0b013e32834bac44.
Lawitz E, Lalezari JP, Hassanein T, Kowdley KV, Poordad FF, Sheikh AM, et al. Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial. Lancet Infect Dis. 2013;13(5):401–8. https://doi.org/10.1016/s1473-3099(13)70033-1.
Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014;383(9916):515–23. https://doi.org/10.1016/s0140-6736(13)62121-2.
Liberto MC, Zicca E, Pavia G, Quirino A, Marascio N, Torti C, et al. Virological mechanisms in the coinfection between HIV and HCV. Mediators Inflamm. 2015;2015:320532. https://doi.org/10.1155/2015/320532.
Lin W, Weinberg EM, Tai AW, Peng LF, Brockman MA, Kim K-A, et al. HIV increases HCV replication in a TGF-beta1-dependent manner. Gastroenterology. 2008;134(3):803–11. https://doi.org/10.1053/j.gastro.2008.01.005.
Luo X, Fan Y, Park I-W, He JJ. Exosomes are unlikely involved in intercellular Nef transfer. PLoS ONE. 2015;10(4):e0124436. https://doi.org/10.1371/journal.pone.0124436.
Marco A, Esteban JI, Solé C, da Silva A, Ortiz J, Roget M, et al. Hepatitis C virus reinfection among prisoners with sustained virological response after treatment for chronic hepatitis C. J Hepatol. 2013;59(1):45–51. https://doi.org/10.1016/j.jhep.2013.03.008.
Martin TCS, Martin NK, Hickman M, Vickerman P, Page EE, Everett R, et al. Hepatitis C virus reinfection incidence and treatment outcome among HIV-positive MSM. AIDS. 2013;27(16):2551–7. https://doi.org/10.1097/QAD.0b013e32836381cc.
Nakano T, Lau GMG, Lau GML, Sugiyama M, Mizokami M. An updated analysis of hepatitis C virus genotypes and subtypes based on the complete coding region. Liver Int. 2012;32(2):339–45. https://doi.org/10.1111/j.1478-3231.2011.02684.x.
Omland LH, Jepsen P, Weis N, Christensen PB, Laursen AL, Nielsen H, 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(4):261–8. https://doi.org/10.1111/j.1365-2893.2009.01175.x.
Park I-W, Fan Y, Luo X, Ryou M-G, Liu J, Green L, et al. HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication. PLoS ONE. 2014;9(6):e99545. https://doi.org/10.1371/journal.pone.0099545.
Parodi C, Belmonte L, Baré P, de Bracco MME, Ruibal-Ares B. Impact of human immune deficiency virus infection on hepatitis C virus infection and replication. Curr HIV Res. 2007;5(1):55–67.
Puoti M, Moioli MC, Travi G, Rossotti R. The burden of liver disease in human immunodeficiency virus-infected patients. Semin Liver Dis. 2012;32(2):103–13. https://doi.org/10.1055/s-0032-1316473.
Rivero-Juarez A, Lopez-Cortes LF, Camacho A, Caruz A, Torres-Cornejo A, Martinez-Dueñas L, et al. The IL28B effect on hepatitis C virus kinetics among HIV patients after the first weeks of pegylated-interferon/ribavirin treatment varies according to hepatitis C virus-1 subtype. AIDS. 2013;27(12):1941–7. https://doi.org/10.1097/QAD.0b013e328360ea1e.
Rockstroh NM, Soriano V, Arastéh K, Guardiola J, Bhagani S, Mallolas J, Tural C, et al. Start verso4 phase 3 trial of faldaprevir plus pegylated interferon α-2a and ribavirin in patients with HIV and HCV genotype-1 co-infection. 64th annual meeting of the American Association for the Study of Liver Diseases. 2013.
Rockstroh J, Teppler H, Zhao J, Sklar P, Harvey C, Strohmaier K, et al. Safety and efficacy of raltegravir in patients with HIV-1 and hepatitis B and/or C virus coinfection. HIV Med. 2012;13(2):127–31. https://doi.org/10.1111/j.1468-1293.2011.00933.x.
Rockstroh JK, Peters L, Grint D, Soriano V, Reiss P, Monforte A, et al. Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV? J Hepatol. 2013;59(2):213–20. https://doi.org/10.1016/j.jhep.2013.04.005.
Sánchez C, Plaza Z, Vispo E, de Mendoza C, Barreiro P, Fernández-Montero JV, et al. Scaling up epidemics of acute hepatitis C and syphilis in HIV-infected men who have sex with men in Spain. Liver Int. 2013;33(9):1357–62. https://doi.org/10.1111/liv.12212.
Sherman KE, Rockstroh J, Thomas D. Human immunodeficiency virus and liver disease: an update. Hepatology. 2015;62(6):1871–82. https://doi.org/10.1002/hep.28150.
Smit C, van den Berg C, Geskus R, Berkhout B, Coutinho R, Prins M. Risk of hepatitis-related mortality increased among hepatitis C virus/HIV-coinfected drug users compared with drug users infected only with hepatitis C virus: a 20-year prospective study. J Acquir Immune Defic Syndr. 2008;47(2):221–5. https://doi.org/10.1097/QAI.0b013e31815d2f59.
Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and genotype assignment web resource. Hepatology. 2014;59(1):318–27. https://doi.org/10.1002/hep.26744.
Soriano V, Sherman KE, Rockstroh J, Dieterich D, Back D, Sulkowski M, et al. Challenges and opportunities for hepatitis C drug development in HIV-hepatitis C virus-co-infected patients. AIDS. 2011;25(18):2197–208. https://doi.org/10.1097/QAD.0b013e32834bbb90.
Thein H-H, 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(15):1979–91. https://doi.org/10.1097/QAD.0b013e32830e6d51.
Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-García J, Lazzarin A, et al. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351(5):438–50. https://doi.org/10.1056/NEJMoa040842.
Vispo E, Fernández-Montero JV, Labarga P, Barreiro P, Soriano V. 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(7):1187–8. https://doi.org/10.1097/QAD.0b013e32835cb815.
Walensky RP, Ross EL, Kumarasamy N, Wood R, Noubary F, Paltiel AD, et al. Cost-effectiveness of HIV treatment as prevention in serodiscordant couples. N Engl J Med. 2013;369(18):1715–25. https://doi.org/10.1056/NEJMsa1214720.
Webster DP, Wojcikiewicz T, Keller M, Castelnovo D, Mistry H, Gilleece Y, et al. Spontaneous clearance and treatment of acute hepatitis C infection in HIV-positive men with 48 weeks of interferon-alpha and ribavirin. Int J STD AIDS. 2013;24(3):179–83. https://doi.org/10.1177/0956462412472317.
Acknowledgements
Authors would like to gratefully acknowledge the facility provided by King Fahd Medical Research Center (KFMRC), King Abdulaziz University, Jeddah, Saudi Arabia.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sohrab, S.S., Suhail, M., Ali, A. et al. Consequence of HIV and HCV co-infection on host immune response, persistence and current treatment options. VirusDis. 29, 19–26 (2018). https://doi.org/10.1007/s13337-018-0424-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13337-018-0424-x