2013, Number 2
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Ann Hepatol 2013; 12 (2)
Response predictors and clinical benefits of hepatitis C retreatment with pegylated interferon and ribavirin in HIV/HCV coinfection
Peribañez-Gonzalez M, Henrique SM, Crivelenti VF, Seixas-Santos NAC, Abrão FP, Focaccia R, Mendes CMC
Language: English
References: 40
Page: 228-235
PDF size: 99.66 Kb.
ABSTRACT
Background. Hepatitis C is a leading cause of mortality among HIV-infected individuals. Therefore, eradication of HCV in this population is a priority. There are scarce data regarding retreatment efficacy of HIV/HCV coinfected patients. The aim of our study was to evaluate efficacy, predictors of response, and long term clinical benefits of sustained virological response (SVR) after hepatitis C retreatment in a population of HIV/HCV coinfected patients.
Material and methods. We evaluated efficacy, safety, and clinical benefits of peginterferon(alfa-2a or alfa-2b) and ribavirin in a restrospective, observational, multicentric study, including 7 HIV/HCV coinfected patients, non-responders to previous treatment with conventional interferon alfa-2a and ribavirin. The primary endpoint of efficacy was SVR, defined as undetectable viral load 24 weeks after end of treatment. Death, liver disease progression, CD4 counts, and AIDS defining illness were the endpoints to access clinical benefits of treatment response.
Results. In our analysis, 31.9% patients reached SVR. Genotypes 2/3 had a significant better SVR (66.7%) compared to genotypes 1/4 (33.3%) (p = 0.022). During follow-up, deaths (6.89%) and hepatic decompensation (28.6%) occurred only in the nonresponder group, while there were no cases of death or hepatic decompensation among the responder group(p = 0.037).
Conclusion. Nearly one third of patients (mainly those with genotypes 2/3) reached SVR after hepatitis C retreatment in this group of HIV/HCV coinfected patients. SVR was protective against hepatic decompensation and death in a two-year follow-up period. Retreatment may be an effective and safe way to eradicate HCV until new anti-HCV drugs become available to this group of patients.
REFERENCES
Benhamou Y, Bochet M, Di Martino V, Charlotte F, Azria F, Coutellier A, Vidaud M, et al. Liver fibrosis progression in HIV and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999; 30: 1054-8.
Alter M. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006; 44(Suppl.): 6-9.
Weber R, Sabin C, Friis-Møller N, Reiss P, El-Sadr WM, Kirk O, Dabis F, et al. Liver-related deaths in persons infected with the HIV: the D:A:D study. Arch Intern Med 2006; 166: 1632-41.
Torriani F, Rodriguez-Torres M, Rockstroh J, Lissen E, Gonzalez-García J, Lazzarin A, Carosi G, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIVinfected patients. N Engl J Med 2004; 351: 438-50.
Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, Morand P,et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients. JAMA 2004; 292: 2839-48.
Laguno M, Murillas J, Blanco JL, Martínez E, Miquel R, Sánchez- Tapias JM, Bargallo X, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS 2004; 18: F27-F36.
Nuñez M , Miralles C, Berdún MA, Losada E, Aguirrebengoa K, Ocampo A, Arazo P, et. al., on behalf of the PRESCO STUDY GROUP. 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.
Martin-Carbonero L, Soriano V, Valencia E, García-Samaniego J, López M, González-Lahoz J. Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients. AIDS Res Hum Retroviruses 2001; 17: 1467-71.
Weber R, Sabin CA, Friis-Møller N, Reiss P, El-Sadr WM, Kirk O, Dabis F, et.al. Liver-Related Deaths in Persons Infected With the Human Immunodeficiency Virus The D:A:D Study: The Data Collection on Adverse Events of Anti-HIV Drugs Study Group*. Arch Intern Med 2006; 166: 1632-41.
Pineda JA, García-García JA, Aguilar-Guisado M, Ríos-Villegas MJ, Ruiz-Morales J, Rivero A, del Valle J,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: 622-30.
Miro JM, Aguero F, Laguno M, Tuset M, Cervera C, Moreno A, Garcia-Valdecasas JC, et al; Hospital Clinic OLT in HIV Working Group. Liver transplantation in HIV/hepatitis coinfection. J HIV Ther 2007; 12: 24-35.
Di Benedetto F, Di Sandro S, De Ruvo N, Berretta M, Montalti R, Guerrini GP, Ballarin R, et al. Human immunodeficiency virus and liver transplantation: our point of view. Transplant Proc 2008; 40: 1965-71.
Mindikoglu AL, Regev A, Magder LS. Impact of human immunodeficiency virus on survival after liver transplantation: analysis of United Network for Organ Sharing database. Transplantation 2008; 85: 359-68.
Duclos-Vallée JC, Roche B, Samuel D. Liver transplantation in patients with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus. Presse Med 2009; 38: 1281-9 [Epub 2009 Jul 1].
Sulkowski M, Pol S, Cooper C, Fainboim H, Slim J, Rivero A, Thompson S, et al. Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients: Interim On-Treatment Results. IDSA Annual Meeting 2011. Boston October 20-23, 2011.
Sulkowski M, Dieterich D, Sherman K, Rockstroh J, Adda N, Mahnke L, Garg V, et al. Interim analysis of a Phase 2a double- blind study of TVR in combination with pegIFN-a2a and RBV in HIV/HCV co-infected patients [Abstract 146LB]. 18th Conference on Retroviruses and Opportunistic Infections. Boston, 2011.
Kasserra C, Hughes E, Treitel M, Gupta S, Edward O’Mara. Clinical Pharmacology of BOC: Metabolism, Excretion, and Drug-Drug Interactions. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011) [Abstract 118]. Boston, February 27-March 2, 2011.
van Heeswijk R, Vandevoorde A, Boogaerts G, Vangeneugden T, de Paepe E, Pólo R, Van Solingen-Ristea R, et al. Pharmacokinetic Interactions between ARV Agents and the Investigational HCV Protease Inhibitor TVR in Healthy Volunteers [Abstract 119]. 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011). Boston, February 27-March 2, 2011.
Myers RP, Benhamou Y, Bochet M, Thibault V, Mehri D, Poynard T. Pegylated interferon alpha 2b and ribavirin in HIV/hepatitis C virus-co-infected non-responders and relapsers to IFN-based therapy. AIDS 2004; 18: 75-9.
Rodriguez-Torres M, Rodriguez-Orengo JF, Rios-Bedoya CF, Fernández-Carbia A, González-Lassalle E, Salgado-Mercado R, Marxuach-Cuétara AM. Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy. J Clin Virol 2007; 38: 32-8.
Crespo M, Mira A, Pineda J, Van den Eyden E, Rios-Villegas MJ, Collado A, Girón-González JA, et.al. Efficacy of Pegilated Interferon and Ribavirin for retreatment of chronic HCV infection in HIV co-infected patientsfailing a previous standard interferon based regimen. J Antimicrob Chemother 2008; 62: 793-6.
Labarga P, Vispo E, Barreiro P, Rodríguez-Novoa S, Pinilla J, Morello J, Martín-Carbonero L, et al. Rate and Predictors of Success in the Retreatment of Chronic Hepatitis C Virus in HIV/Hepatitis C Virus Coinfected Patients With Prior Nonresponse or Relapse. J Acquir Immune Defic Syndr 2010; 53: 364-8.
Labarga P, Barreiro P, Mira JA, Vispo E, Rallón N, Neukam K, Camacho A, et al. Impact of IL28B polymorphisms on response to peginterferon and ribavirin in HIV-hepatitis C virus-coinfected patients with prior nonresponse or relapse. AIDS 2011; 25: 1131-3.
Berenguer J, Alvarez-Pellicer J, Martín PM, López-Aldeguer J, Von-Wichmann MA, Quereda C, Mallolas J, et al., and The GESIDA3603/5607 Study Group. 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.
Hornberger J, Torriani FJ, Dieterich DT, Bräu N, Sulkowski MS, Torres MR, Green J, Patel K, et al. Cost effectiveness of peginterferon alfa-2a (40kDa) plus ribavirin in patients with HIV and hepatitis C virus co-infection. J Clin Virol 2006; 36: 283-91.
Sroczynski G., Esteban E, Conrads-Frank A., Schwarzer R, Mühlberger N, Wright D, Zeuzem S, Siebert U. Long-term effectiveness and cost-effectiveness of antiviral treatment in hepatitis C. J Viral Hepat 2010; 17: 34-50.
Kuehne FC, Bethe U, Freedberg K, Goldie SJ. Treatment for Hepatitis C Virus in Human Immunodeficiency Virus-Infected Patients Clinical Benefits and Cost-effectiveness. Arch Intern Med 2002; 162: 2545-56.
Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde.Departamento de DST, Aids e Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para o tratamento da hepatite viral crônica B e coinfecções. Brasília: Ministério da Saúde, 2005.
CDC 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. MMWR 1992; 41(No. RR-17).
Nicot F, Legrand-Abravanel F, Lafont T, Dubois M, Sauné K, Pasquier C, Chatelut E, Izopet J. Serum Concentration of Ribavirin and Pegylated Interferon and Viral Responses in Patients Infected. With HIV and HCV. J Med Virol 2008; 80: 1523-9.
Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 2004; 4: 583-94.
Macias J, Japon MA, Saez C, Palacios RB, Mira JA, García-García JA, Merchante N, et al. Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection. J Infect Dis 2005; 192: 1566-76.
Balagopal A, Philp FH, Astemborski J, Block TM, Mehta A, Long R, Kirk GD, et al. Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology 2008; 135: 226-33.
Balagopal A, Raya SC, De Ocab R M, Sutcliffe CG, Vivekanandan P, Higgins Y, Mehta SH, et al. Kupffer cells are depleted with HIVimmunodeficiency and partially recovered with antiretroviral immune reconstitution. AIDS 2009; 23: 2397-404.
Miller MF, Haley C, Koziel MJ, Rowley CF. Impact of hepatitis C virus on immune restoration in HIV-infected patients who start highly active antiretroviral therapy: a metaanalysis. Clin Infect Dis 2005; 41: 713-20.
Nunez M, Soriano V, Lopez M, Ballesteros C, Cascajero A, González-Lahoz J, Benito JM. Coinfection with hepatitis C virus increases lymphocyte apoptosis in HIV-infected patients. Clin Infect Dis 2006; 43: 1209-12.
Körner C, Krämer B, Schulte D, Coenen M, Mauss S, Fätkenheuer G, Oldenburg J, et al. Effects of HCV co-infection on apoptosis of CD4+ T-cells in HIV-positive patients. Clin Sci (Lond) 2009; 116: 861-70.
Gonzalez VD, Landay AL, Sandberg JK. Innate immunity and chronic immune activation in HCV/HIV-1 co-infection. Clin Immunol 2010; 135: 12-25 [Epub 2010 Jan 25].
Körner C, Tolksdorf F, Riesner K, Krämer B, Schulte D, Nattermann J, Rockstroh JK, Spengler U. Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fasinduced apoptosis in viraemic and HAART-controlled HIV-1-positive patients. Antivir Ther 2011; 16: 1047-55.
Kim AY, Chung RT. Coinfection With HIV-1 and HCV-A One-Two Punch. Gastroenterology 2009; 137: 795-814.