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Published in: Infection 1/2016

01-02-2016 | Original Paper

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome

Authors: Christoph Boesecke, Patrick Ingiliz, Thomas Reiberger, Hans-Jürgen Stellbrink, Sanjay Bhagani, Emma Page, Stefan Mauss, Thomas Lutz, Esther Voigt, Marguerite Guiguet, Marc-Antoine Valantin, Axel Baumgarten, Mark Nelson, Martin Vogel, Jürgen K. Rockstroh, The NEAT study group

Published in: Infection | Issue 1/2016

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Abstract

Purpose

With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome.

Methods

303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30).

Results

All patients were male, median age was 39 years. Main routes of transmission were MSM (95 %) and IVDU (3 %). 69 % of patients were infected with HCV GT 1, 4.3 % with GT 2, 10.6 % with GT 3, 16.1 % with GT 4. Overall SVR rate was 69.3 % (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94 % vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR.

Conclusions

Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.
Literature
1.
go back to reference 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:F1–7.CrossRefPubMed 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:F1–7.CrossRefPubMed
2.
go back to reference Fierer D, Fishman S, Uriel A, et al. Characterization of an outbreak of acute HCV infection in HIV-infected men in New York city. In: 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Canada; 2009; abstract 802. Fierer D, Fishman S, Uriel A, et al. Characterization of an outbreak of acute HCV infection in HIV-infected men in New York city. In: 16th Conference on Retroviruses and Opportunistic Infections; Montreal, Canada; 2009; abstract 802.
3.
go back to reference 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;41:31–6.PubMedCentralCrossRefPubMed 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;41:31–6.PubMedCentralCrossRefPubMed
4.
go back to reference Matthews G, Hellard M, Haber P, et al. Characteristics and treatment outcomes among HIV-infected individuals in the Australian trial in acute hepatitis C. Clin Infect Dis. 2009;48:650–8.PubMedCentralCrossRefPubMed Matthews G, Hellard M, Haber P, et al. Characteristics and treatment outcomes among HIV-infected individuals in the Australian trial in acute hepatitis C. Clin Infect Dis. 2009;48:650–8.PubMedCentralCrossRefPubMed
5.
go back to reference Yaphe S, Bozinoff N, Kyle R, Shivkumar S, Pai NP, Klein M. Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review. Sex Transm Infect. 2012;88:558–64.CrossRefPubMed Yaphe S, Bozinoff N, Kyle R, Shivkumar S, Pai NP, Klein M. Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review. Sex Transm Infect. 2012;88:558–64.CrossRefPubMed
6.
7.
go back to reference Jones L, Uriel A, Kaplan D, et al. Natural history and treatment outcome of acute hepatitis C with and without HIV co-infection in a North American cohort. In: AASLD 2008 Meeting; San Francisco, USA; 2008; abstract 1838. Jones L, Uriel A, Kaplan D, et al. Natural history and treatment outcome of acute hepatitis C with and without HIV co-infection in a North American cohort. In: AASLD 2008 Meeting; San Francisco, USA; 2008; abstract 1838.
8.
go back to reference Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284:450–6.CrossRefPubMed Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284:450–6.CrossRefPubMed
9.
go back to reference Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284:450–6.CrossRefPubMed Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284:450–6.CrossRefPubMed
10.
go back to reference Soriano V, Mocroft A, Rockstroh J, et al. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe. J Infect Dis. 2008;198:1337–44.CrossRefPubMed Soriano V, Mocroft A, Rockstroh J, et al. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe. J Infect Dis. 2008;198:1337–44.CrossRefPubMed
11.
go back to reference Gilleece YC, Browne RE, Asboe D, et al. Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin. J Acquir Immune Defic Syndr. 2005;40:41–6.CrossRefPubMed Gilleece YC, Browne RE, Asboe D, et al. Transmission of hepatitis C virus among HIV-positive homosexual men and response to a 24-week course of pegylated interferon and ribavirin. J Acquir Immune Defic Syndr. 2005;40:41–6.CrossRefPubMed
12.
go back to reference 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;60:837–45.PubMedCentralCrossRefPubMed 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;60:837–45.PubMedCentralCrossRefPubMed
13.
14.
go back to reference Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology. 2010;138:e1331–7.CrossRef Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology. 2010;138:e1331–7.CrossRef
15.
go back to reference Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.CrossRefPubMed Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.CrossRefPubMed
16.
go back to reference Grebely J, Petoumenos K, Hellard M, ATAHC Study Group, et al. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology. 2010;52:1216–24.PubMedCentralCrossRefPubMed Grebely J, Petoumenos K, Hellard M, ATAHC Study Group, et al. Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection. Hepatology. 2010;52:1216–24.PubMedCentralCrossRefPubMed
17.
go back to reference Vogel M, Boesecke C, Rockstroh JK. Acute hepatitis C infection in HIV-positive patients. Curr Opin Infect Dis. 2011;24(1):1–6.CrossRefPubMed Vogel M, Boesecke C, Rockstroh JK. Acute hepatitis C infection in HIV-positive patients. Curr Opin Infect Dis. 2011;24(1):1–6.CrossRefPubMed
18.
go back to reference Vogel M, Page E, Matthews G, et al. Use of week 4 HCV RNA after acute HCV infection to predict chronic HCV infection. In: 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, California, USA; 2010; abstract 640. Vogel M, Page E, Matthews G, et al. Use of week 4 HCV RNA after acute HCV infection to predict chronic HCV infection. In: 17th Conference on Retroviruses and Opportunistic Infections; San Francisco, California, USA; 2010; abstract 640.
19.
go back to reference Gerlach JT, Diepolder HM, Zachoval R, et al. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003;125:80–8.CrossRefPubMed Gerlach JT, Diepolder HM, Zachoval R, et al. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003;125:80–8.CrossRefPubMed
20.
go back to reference The European AIDS Treatment Network (NEAT). Acute Hepatitis C Infection Consensus Panel. Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS. 2011;25:399–409. The European AIDS Treatment Network (NEAT). Acute Hepatitis C Infection Consensus Panel. Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference. AIDS. 2011;25:399–409.
21.
go back to reference Deterding K, Gruner NH, Wiegand J, et al. Early versus delayed treatment of acute hepatitis C: the German HEP-NET Acute HCV-III study—a randomized controlled trial. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) 2009: abstract 1047. Deterding K, Gruner NH, Wiegand J, et al. Early versus delayed treatment of acute hepatitis C: the German HEP-NET Acute HCV-III study—a randomized controlled trial. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) 2009: abstract 1047.
22.
go back to reference Nomura H, Sou S, Tanimoto H, et al. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004;39:1213–9.CrossRefPubMed Nomura H, Sou S, Tanimoto H, et al. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004;39:1213–9.CrossRefPubMed
23.
go back to reference Vogel M, Nattermann J, Baumgarten A, et al. Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals. Antivir Ther. 2006;11:1097–101.PubMed Vogel M, Nattermann J, Baumgarten A, et al. Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals. Antivir Ther. 2006;11:1097–101.PubMed
24.
go back to reference Dominguez S, Ghosn J, Valantin MA, et al. Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients. AIDS. 2006;20:1157–61.CrossRefPubMed Dominguez S, Ghosn J, Valantin MA, et al. Efficacy of early treatment of acute hepatitis C infection with pegylated interferon and ribavirin in HIV-infected patients. AIDS. 2006;20:1157–61.CrossRefPubMed
25.
go back to reference Kruk A. Efficacy of acute HCV treatment with peg-interferon alfa-2b and ribavirin in HIV-infected patients. In: 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; Rio de Janeiro; 2005; abstract TuPe1.C01. Kruk A. Efficacy of acute HCV treatment with peg-interferon alfa-2b and ribavirin in HIV-infected patients. In: 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment; Rio de Janeiro; 2005; abstract TuPe1.C01.
26.
go back to reference Piroth L, Larsen C, Binquet C, Steering Committee of the HEPAIG Study, et al. Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: the HEPAIG study. Hepatology. 2010;52:1915–21. doi:10.1002/hep.23959.CrossRefPubMed Piroth L, Larsen C, Binquet C, Steering Committee of the HEPAIG Study, et al. Treatment of acute hepatitis C in human immunodeficiency virus-infected patients: the HEPAIG study. Hepatology. 2010;52:1915–21. doi:10.​1002/​hep.​23959.CrossRefPubMed
27.
go back to reference Laguno M, Martínez-Rebollar M, Perez I, et al. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients. AIDS Res Hum Retroviruses. 2012;28:1294–300.CrossRefPubMed Laguno M, Martínez-Rebollar M, Perez I, et al. Low rate of sustained virological response in an outbreak of acute hepatitis C in HIV-infected patients. AIDS Res Hum Retroviruses. 2012;28:1294–300.CrossRefPubMed
28.
go back to reference Dorward J, Garrett N, Scott D, et al. 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;52:367–9 Epub 2011 Sep 15.CrossRefPubMed Dorward J, Garrett N, Scott D, et al. 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;52:367–9 Epub 2011 Sep 15.CrossRefPubMed
29.
go back to reference Wiegand J, et al. Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute–HCV–II study. Hepatology. 2006;43:250–6.CrossRefPubMed Wiegand J, et al. Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute–HCV–II study. Hepatology. 2006;43:250–6.CrossRefPubMed
30.
go back to reference Arends JE, van Assen S, Stek CJ, et al. Pegylated interferon-α monotherapy leads to low response rates in HIV-infected patients with acute hepatitis C. Antivir Ther. 2011;16:979–88.CrossRefPubMed Arends JE, van Assen S, Stek CJ, et al. Pegylated interferon-α monotherapy leads to low response rates in HIV-infected patients with acute hepatitis C. Antivir Ther. 2011;16:979–88.CrossRefPubMed
31.
go back to reference Nunez M, Miralles C, Berdun 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.CrossRefPubMed Nunez M, Miralles C, Berdun 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.CrossRefPubMed
32.
go back to reference Matthews G, Grebely J, Hellard M, et al. Differences in early virological decline in individuals treated within the Australian trial in acute HCV suggest a potential benefit for the use of ribavirin. In: 45th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, Austria; 2010: abstract O60. Matthews G, Grebely J, Hellard M, et al. Differences in early virological decline in individuals treated within the Australian trial in acute HCV suggest a potential benefit for the use of ribavirin. In: 45th Annual Meeting of the European Association for the Study of the Liver (EASL). Vienna, Austria; 2010: abstract O60.
33.
go back to reference Hare B, Marks K, Luetkemeyer A, et al. Kinetically guided PEG Alfa-2a and RBV therapy for HIV+adults with acute HCV infection. In: 17th Conference on Retroviruses and Opportunistic Infection; San-Francisco, California, USA; 2010; abstract 639. Hare B, Marks K, Luetkemeyer A, et al. Kinetically guided PEG Alfa-2a and RBV therapy for HIV+adults with acute HCV infection. In: 17th Conference on Retroviruses and Opportunistic Infection; San-Francisco, California, USA; 2010; abstract 639.
34.
go back to reference Nattermann J, Vogel M, Nischalke HD, et al. Genetic variation in IL28B and treatment-induced clearance of hepatitis C Virus in HIV-positive patients with acute and chronic hepatitis C. J Infect Dis. 2011. Nattermann J, Vogel M, Nischalke HD, et al. Genetic variation in IL28B and treatment-induced clearance of hepatitis C Virus in HIV-positive patients with acute and chronic hepatitis C. J Infect Dis. 2011.
35.
go back to reference Lambers F, van den Berk G, van der Meer J, et al. Treatment outcome of acute HCV infection in HIV-infected MSM: effect of treatment length. In: 17th Conference on Retroviruses and Opportunistic Infections. San-Francisco, California, USA; 2010: abstract 641. Lambers F, van den Berk G, van der Meer J, et al. Treatment outcome of acute HCV infection in HIV-infected MSM: effect of treatment length. In: 17th Conference on Retroviruses and Opportunistic Infections. San-Francisco, California, USA; 2010: abstract 641.
36.
go back to reference Vogel M, Dominguez S, Bhagani S, et al. Treatment of acute HCV infection in HIV-positive patients: experience from a multicentre European cohort. Antivir Ther. 2010;15:267–79.CrossRefPubMed Vogel M, Dominguez S, Bhagani S, et al. Treatment of acute HCV infection in HIV-positive patients: experience from a multicentre European cohort. Antivir Ther. 2010;15:267–79.CrossRefPubMed
37.
go back to reference Fierer DS, Dieterich DT, Mullen MP, et al. Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men. Clin Infect Dis. 2014;58:873–9.PubMedCentralCrossRefPubMed Fierer DS, Dieterich DT, Mullen MP, et al. Telaprevir in the treatment of acute hepatitis C virus infection in HIV-infected men. Clin Infect Dis. 2014;58:873–9.PubMedCentralCrossRefPubMed
38.
go back to reference European AIDS Clinical Society (EACS). Guidelines Version 7.1. November 2014. European AIDS Clinical Society (EACS). Guidelines Version 7.1. November 2014.
39.
go back to reference Tillmann HL, Thompson AJ, Patel K, et al. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology. 2010;139:1586–92 1592.e1.CrossRefPubMed Tillmann HL, Thompson AJ, Patel K, et al. A polymorphism near IL28B is associated with spontaneous clearance of acute hepatitis C virus and jaundice. Gastroenterology. 2010;139:1586–92 1592.e1.CrossRefPubMed
40.
go back to reference Boesecke C, van Assen S, Stellbrink HJ, et al. Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection. J Viral Hepat. 2014;21:780–5.CrossRefPubMed Boesecke C, van Assen S, Stellbrink HJ, et al. Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection. J Viral Hepat. 2014;21:780–5.CrossRefPubMed
41.
go back to reference Grebely J, Hellard M, Applegate T, et al. Virological responses during treatment for recent hepatitis C virus: potential benefit for ribavirin use in HCV/HIV co-infection. AIDS. 2012;26:1653–61.PubMedCentralCrossRefPubMed Grebely J, Hellard M, Applegate T, et al. Virological responses during treatment for recent hepatitis C virus: potential benefit for ribavirin use in HCV/HIV co-infection. AIDS. 2012;26:1653–61.PubMedCentralCrossRefPubMed
Metadata
Title
Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome
Authors
Christoph Boesecke
Patrick Ingiliz
Thomas Reiberger
Hans-Jürgen Stellbrink
Sanjay Bhagani
Emma Page
Stefan Mauss
Thomas Lutz
Esther Voigt
Marguerite Guiguet
Marc-Antoine Valantin
Axel Baumgarten
Mark Nelson
Martin Vogel
Jürgen K. Rockstroh
The NEAT study group
Publication date
01-02-2016
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 1/2016
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-015-0856-9

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