- Email: [email protected]
826 ANTIVIRAL TREATMENT OF HCV CARRIERS WITH NORMAL ALT
05G. VIRAL HEPATITIS – G) HEPATITIS C – CLINICAL (THERAPY) 824 ABACAVIR HAS A NEGATIVE IMPACT ON RAPID VIROLOGIC RESPONSE TO PEGYLATED INTERFERON AND RIBAVIRRIN COMBINATION TREATMENT OF HEPATITIS C IN HIV-1 COINFECTED PATIENTS M. Puoti1 , P. Sacchi2 , P. Nasta1 , G. Cariti3 , I. Maida4 , N. Ladisa5 , A. De Bona6 , C. Iannacone7 , G. Di Perri3 , M. Toti8 , R. Bruno2 . 1 Department of Infectious Diseases, Spedali Civili, University of Brescia, 2 Infectious Diseases and Topical Medicine, Fondazione Policlinico San Matteo, University of Pavia, 3 Department of Infectious Diseases, Ospedale “Amedeo di Savoia” University of Torino, 4 Institute of Infectious Diseases, University of Sassari, 5 Department of Infectious Diseases, Policlinico, University of Bari, 6 Department of Infectious Diseases, “Vita e Salute” University, Ospedale San Raffaele, Milan;, 7 Quintiles Italy, Milano, 8 Department of Infectious Diseases, Ospedale di Grosseto, ITALY E-mail: [email protected];[email protected] Background: Ribavirin use and higher ribavirin doses are associated with accelerated viral decay during the very early phase of ant-HCV therapy. An interference of abacavir with ribavirin intracellular phosphorilation has been hypothesized. Thus, concurrent abacavir use should impair the early phases of viral decay during anti HCV treatment. A negative interaction seem to be confirmed by preliminary data from retrospective studies showing a negative impact of abacavir use on the sustained response to pegylated interferon and ribavirin combination treatment in HIV infected patients with chronic hepatitis C. However this association could be biased by confounders and not due to a reduced potency of anti HCV treatment. Aims and Methods: We analyzed the impact of concurrent abacavir use on the rate of Rapid Virologic Response (HCV-RNA <50 IU/mL after 4 weeks) in 337 patients from a large observational multicenter cohort study treated with ribavirin >10.6 mg/kg/d in combination with Pegylated Interferon alfa 2b 1.5 mcg/Kg or Pegylated Interferon alfa 2a 180 mcg per week and with an available measurement of HCV-RNA after 4 weeks of treatment. Mann Whitney or t-test and Fisher’s exact test were used for bivariate analysis when indicated. Logistic regression was used for multivariate analysis. Results: RVR was observed in 25%. Abacavir was prescribed in 55 subjects (16%): 14% of them showed RVR [OR 0.46 (95 CI 0.21−1.02) p = 0.06]. In multivariate analysis abacavir use was associated with RVR [Adjusted OR 0.43 (95 CI 0.18−0.99) p = 0.049] after adjusting for HCV genotype, age, HCV-RNA levels, zidovudine use and ribavirin dose per Kg of body weight. Abacavir use was not associated with a lower decline of haemoglobin after 4 weeks (mean±SD was 2.1±1.5 g/L in those treated with abacavir vs. 2.0±1.3 g/L in those not exposed to abacavir). Conclusions: Abacavir use was associated with an impaired antiviral effect of Pegylated Interferon and ribavirin in HIV infected patients. If this interaction is due to competition for intracellular phosphorilation this should not occur in erythrocytes. In fact haemolytic anaemia that is caused by accumulation of ribavirin triphosphate in red blood cells is not reduced by concurrent abacavir treatment.
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825 RESULTS OF A RANDOMIZED CONTROLLED TRIAL ON THE IMPACT OF PROLONGED COMBINATION ANTI-HCV TREATMENT IN HIV/HCV CO-INFECTED PATIENTS M. Puoti1 , B. Zanini1 , A. De Luca2 , G.P. Quinzan3 , R. Allegri4 , R. Bruno5 , A. Orani6 , T. Quirino7 , T. Santantonio8 , G. Pastore8 , G. Cristini4 , F. Suter3 , R. Cauda2 , G. Carosi1 . 1 Institute of Infectious and Tropical Diseases University of Brescia, Brescia, 2 Department of Infectious Diseases, UCSC Rome, Rome, 3 Department of Infectious Diseases Ospedali Riuniti, Bergamo, 4 Department of Infectious Diseases, University of Pavia, Pavia, 5 Department of Infectious Diseases, Lecco, 6 Department of Infectious Diseases, Busto Arsizio, Italy E-mail: [email protected];[email protected] Background: Relapse is frequent in HIV-HCV co-infected persons treated with pegylated interferon and ribavirin. In order to explore the possibility that a prolonged treatment duration could decrease relapse rate in HIV/HCV coinfected patients with a negative HCVRNA at the end of a regular treatment course we have performed a multicenter open randomised controlled trial. Methods: All consecutive patients with a negative HCV RNA (<50 IU/mL Cobas Amplicore Roche) after 24 (Genotype 3) or 48 (genotype 1 and 4) weeks of anti HCV treatment with Pegylated Interferon alfa 2a at 180 mcg/w in combination with weight adjusted ribavirin (800–1200 mg) have been randomised at the 28th (genotype 2 or 3) or 52nd (genotype 1 or 4) week of treatment to stop therapy (Arm A) or to prolong treatment for additional 20 weeks (Arm B). Results: One hundred and twenty patients have been enrolled in this trial from 2002 to 2004 (23% female, 41% with advanced fibrosis and 53% with HCV RNA >6 log IU/mL): 63 were randomized to arm A (25 HCV G1−4) and 57 to arm B (25 HCV G1−4). Twenty-one from Arm B (37%) prematurely stopped treatment: 7 had SAE (3 G1−4) and 14 dropped out (5 G1−4). SVR was obtained in 38 patients (60%) in Arm A (60% in G1−4 and 60% in G2−3) and in 40 (70%) in Arm B (64% in G1−4 and 80% in G2−3) (p > 0.05 Arm A vs Arm B). Per protocol analysis showed a significantly higher SVR rate only in patients with G2−3 (90% vs. 60% p = 0.04). Multivariate analysis showed that baseline HCV RNA >600,000 IU/mL (AOR 0.24, 95% CI 0.1−0.62) and HCV RNA negativization after 4 weeks (Rapid Virologic Response RVR; AOR 4.30, 95 CI 1.67−11.2) were independently associated with SVR. Among the patients with HCV G3 and without RVR or with baseline HCV RNA >600,000 IU/mL 14/29 showed SVR in arm A and 11/13 in Arm B (p = 0.03). Conclusions: An increased duration of anti HCV treatment could be beneficial in patients infected by HCV genotype 2−3 with high baseline viremia and/or without RVR. 826 ANTIVIRAL TREATMENT OF HCV CARRIERS WITH NORMAL ALT C. Puoti1 , A.M. Pellicelli2 , M. Romano3 , R. Guarisco1 , F. Mecenate4 , G. Barbarini5 , E. Mazzoni6 , A. Barlattani7 , A. Picardi8 , A. Paffetti9 , L. Nosotti10 , M.E. Bonaventura9 , R. Villani2 , L. Bellis1 , S. Nicodemo1 , L. Spilabotti1 , F. Soccorsi2 . 1 Department of Internal Medicine and Liver Unit, Marino Hospital, Rome, 2 Liver Unit, S. Camillo-Forlanini Hospital, Rome, 3 Liver Unit, Sandro Pertini Hospital, Rome, 4 Liver Unit, Villa Betania Hospital, Rome, 5 Department of Infectious and Parasitic Diseases, Policlinico S. Matteo, Pavia, 6 Liver Unit, Policlinico Casilino Hospital, Rome, 7 Department of Internal Medicine, S. Giacomo Hospital, Rome, 8 Liver Unit, Campus Biomedico University, Rome, 9 Departments of Infectious Diseases, 1st University of Rome, Rome, 10 Department of Preventive Medicine of Migration, Tourism and Tropical Dermatology, S. Gallicano Hospital, Rome, Italy E-mail: [email protected] Background: Treatment with PEG-IFN plus RBV of HCV carriers with persistently normal ALT levels (PNALT) has been discouraged outside
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clinical trials. Only one trial (Zeuzem 2004) evaluated the efficacy of this therapy in PNALT; however, HCV-1 subjects were treated with low RBV dose (800 mg/day). Thus, the efficacy of the approved dosage of RBV (1000–1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Simulations based on generalised additive model (GAM) analysis suggest that SVR in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of ribavirin is administered (Snoeck et al, 2007). Aims of this study were (i) to evaluate the overall virological responses (EoTR, SVR) to combined antiviral treatment in HCV patients with PNALT, and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000–1200 mg/day) might achieve higher EVR than those obtained in previous RCT with lower RBV doses. Patients. 88 PNALT (53 females, range 22−60 yrs) were studied. 32 patients did harbour HCV type 1, 46 HCV-2, and 10 had HCV-3. Liver biopsy was performed in 72 patients, showing minimal fibrosis in all but 3 patients (F0−F1 Metavir). All patients received PEG interferon alfa2a 180 mg/wk plus RBV 800 mg/day for 24 wks (HCV 2 and 3 patients) or 1000–1200 mg/day for 48 wks (HCV-1 patients, according to bw). Persistent ALT normality was defined by at least 3 normal values two months apart over a 6 mo. observation period. Results: EoTR was seen in 81/88 pts (82%; 84% of HCV-1, 100% of HCV-2, 90% of HCV-3). To date, SVR has been evaluated in 63 pts (24 HCV-1 and 39 HCV-2); virological response was maintained in 37/39 HCV-2 patients (SVR 95%) and in 20/24 HCV-1 patients (83%). Side effects were not different from those observed among patients with elevated ALT levels treated in the same period. Conclusions. Antiviral treatment with PEG IFN plus RBV is safe and effective in patients with PNALT. Using standard RBV doses in patients with HCV-1, rates of SVR higher than those seen in patients with abnormal ALT can be achieved.
827 EFFICACY OF PEGINTERFERON ALPHA-2a AND RIBAVIRIN IN HIV/HCV CO-INFECTED PATIENTS: SUBANALYSIS OF HEPATYS, FRENCH NATIONAL SURVEY I. Ravaux1 , D. Ouzan2 , M. Rosenheim3 , M. Doffoel4 , P. Marcellin5 , J.M. Pawlotsky6 , C. Hayem7 , A. Pinta7 , M. Vray8 , M. Bourliere9 . 1 Infectious disease department, la Conception Hospital, Marseille, 2 Hepatology Unit, Tzank Institut, St Laurent du Var, 3 Infectious Disease Department, Piti´e-Salpˆetri`ere Hospital, Paris, 4 Hepatology Department, Civil Hospital, Strasbourg, 5 Hepatology Department, Beaujon Hospital, Clichy, 6 Virology Department, Henri Mondor Hospital, Creteil, 7 Roche, Neuilly, 8 Pasteur Institute, Paris, 9 Hepatology department, Saint-Joseph Hospital, France E-mail: [email protected] Background: In 2003, a longitudinal, multicenter prospective survey was initiated in order to assess the use and efficacy of Peginterferon alpha-2a in real life in chronic hepatitis C patients. Methods: Between November 2003 and December 2004, 334 physicians involved in C hepatitis management have included patients for whom a Peginterferon alpha-2a treatment was decided. Clinical and biological data were recorded at baseline and every three months, as well as PCR three months after the end of treatment for sustained virological response (SVR) evaluation. Results: Data from a total of 2101 patients were analyzed. Among these patients, 108 (5%) where HIV co-infected followed in hospital (87%) and in liberal practice (13%). Patients demography was as follows: mainly men (67%), mean age (±SD) 42 (±6) years, mean weight 67 (±13) Kg and 69% had a past history of injecting drug abuse. Regarding HIV infection, CD4 cells median was 407/mm3 and 84% of the patients received antiretroviral treatment. Previous or actual depression was present in 36% of the patients and an antidepressant treatment was prescribed in 26%. Almost every patient (93%, 100/108) had a liver disease evaluation, 81% (88/108) by liver biopsy. Cirrhosis was present in 23%. Genotypic
repartition was as follows: G1 48%, G2 4%, G3 35%, G4 11%, G5 1%. Majority of patients (64%) had never been treated. Higher doses of ribavirin (1000/1200 mg/day) were prescribed in 45% of the patients. SVR rates were obtained overall in 45% (37/83) and in 50% (24/48) of naive patients (36% for G1, 69% for G2,3). Patients with moderate or severe fibrosis had lower SVR rates compared to patients with minimal or no fibrosis: F0 100% (2/2), F1 67% (12/18), F2 44% (8/18) F3 42% (8/19) F4 31% (5/16). Conclusion: Efficacy of Peginterferon alpha-2a plus ribavirin used in real conditions in HIV/HCV co-infected patients is comparable to Presco trial results. 828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE K.R. Reddy1 , D. Messinger2 , M. Popescu3 , S.J. Hadziyannis4 . 1 Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; 2 IST GmbH, Mannheim, Germany; 3 Roche, Basel, Switzerland; 4 Henry Dunant Hospital, Athens, Greece E-mail: [email protected] Background: The demographics of HCV infection are shifting, with an increasing number of patients now over 50 years of age. To assess the impact of age on sustained virological response (SVR) we analyzed the data from two large phase III studies of PEG-IFN a-2a (40KD) plus ribavirin (RBV) (NV15942 and NV15801). Methods: Patients included in this analysis were HCV genotype 1 and had received 48 weeks of treatment with PEG-IFN a-2a (40KD) 180 mg/wk plus RBV 1000/1200 mg/day. SVR was defined as undetectable HCV RNA by qualitative PCR after 24 weeks of untreated follow-up. Results: Overall, the SVR rate in patients 50 years was 52% (n = 438) and 39% in the 131 patients who were >50 years (p = 0.007). SVR rates in patients aged >50 years were heterogeneous and varied according to previously well-established prognostic factors. In particular, SVR rates were higher in older patients without advanced fibrosis (44%), those with low baseline serum HCV RNA levels (57%), those patients who received 80% of the planned dose of PEG-IFN (53%) and those patients who received 60% of the planned dose of RBV (53%). Age did not influence whether patients completed therapy (76% of patients 50 years vs. 73% of patients >50 years [p = 0.6]). However, there was a trend towards lower cumulative PEG-IFN exposure in older patients (7235 mg in patients 50 vs. 6868 mg in patients >50 years [p = 0.0986]) and a significantly lower cumulative RBV exposure in older patients (304 g in patients 50 vs. 252 g in patients >50 [p < 0.0001]). In our study more patients >50 years had dose reductions resulting in <60% of target RBV exposure than patients 50 years (38% vs. 22%). Discontinuation rates due to any AE were similar in those 50 years (11%) and those >50 years (12%). Conclusions: SVR rates in subgroups of older patients with positive prognostic factors (such as those without advanced fibrosis, low HCV RNA levels) are comparable to younger patients, especially if high rates of adherence can be maintained.
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825 RESULTS OF A RANDOMIZED CONTROLLED TRIAL ON THE IMPACT OF PROLONGED COMBINATION ANTI-HCV TREATMENT IN HIV/HCV CO-INFECTED PATIENTS M. Puoti1 , B. Zanini1 , A. De Luca2 , G.P. Quinzan3 , R. Allegri4 , R. Bruno5 , A. Orani6 , T. Quirino7 , T. Santantonio8 , G. Pastore8 , G. Cristini4 , F. Suter3 , R. Cauda2 , G. Carosi1 . 1 Institute of Infectious and Tropical Diseases University of Brescia, Brescia, 2 Department of Infectious Diseases, UCSC Rome, Rome, 3 Department of Infectious Diseases Ospedali Riuniti, Bergamo, 4 Department of Infectious Diseases, University of Pavia, Pavia, 5 Department of Infectious Diseases, Lecco, 6 Department of Infectious Diseases, Busto Arsizio, Italy E-mail: [email protected];[email protected] Background: Relapse is frequent in HIV-HCV co-infected persons treated with pegylated interferon and ribavirin. In order to explore the possibility that a prolonged treatment duration could decrease relapse rate in HIV/HCV coinfected patients with a negative HCVRNA at the end of a regular treatment course we have performed a multicenter open randomised controlled trial. Methods: All consecutive patients with a negative HCV RNA (<50 IU/mL Cobas Amplicore Roche) after 24 (Genotype 3) or 48 (genotype 1 and 4) weeks of anti HCV treatment with Pegylated Interferon alfa 2a at 180 mcg/w in combination with weight adjusted ribavirin (800–1200 mg) have been randomised at the 28th (genotype 2 or 3) or 52nd (genotype 1 or 4) week of treatment to stop therapy (Arm A) or to prolong treatment for additional 20 weeks (Arm B). Results: One hundred and twenty patients have been enrolled in this trial from 2002 to 2004 (23% female, 41% with advanced fibrosis and 53% with HCV RNA >6 log IU/mL): 63 were randomized to arm A (25 HCV G1−4) and 57 to arm B (25 HCV G1−4). Twenty-one from Arm B (37%) prematurely stopped treatment: 7 had SAE (3 G1−4) and 14 dropped out (5 G1−4). SVR was obtained in 38 patients (60%) in Arm A (60% in G1−4 and 60% in G2−3) and in 40 (70%) in Arm B (64% in G1−4 and 80% in G2−3) (p > 0.05 Arm A vs Arm B). Per protocol analysis showed a significantly higher SVR rate only in patients with G2−3 (90% vs. 60% p = 0.04). Multivariate analysis showed that baseline HCV RNA >600,000 IU/mL (AOR 0.24, 95% CI 0.1−0.62) and HCV RNA negativization after 4 weeks (Rapid Virologic Response RVR; AOR 4.30, 95 CI 1.67−11.2) were independently associated with SVR. Among the patients with HCV G3 and without RVR or with baseline HCV RNA >600,000 IU/mL 14/29 showed SVR in arm A and 11/13 in Arm B (p = 0.03). Conclusions: An increased duration of anti HCV treatment could be beneficial in patients infected by HCV genotype 2−3 with high baseline viremia and/or without RVR. 826 ANTIVIRAL TREATMENT OF HCV CARRIERS WITH NORMAL ALT C. Puoti1 , A.M. Pellicelli2 , M. Romano3 , R. Guarisco1 , F. Mecenate4 , G. Barbarini5 , E. Mazzoni6 , A. Barlattani7 , A. Picardi8 , A. Paffetti9 , L. Nosotti10 , M.E. Bonaventura9 , R. Villani2 , L. Bellis1 , S. Nicodemo1 , L. Spilabotti1 , F. Soccorsi2 . 1 Department of Internal Medicine and Liver Unit, Marino Hospital, Rome, 2 Liver Unit, S. Camillo-Forlanini Hospital, Rome, 3 Liver Unit, Sandro Pertini Hospital, Rome, 4 Liver Unit, Villa Betania Hospital, Rome, 5 Department of Infectious and Parasitic Diseases, Policlinico S. Matteo, Pavia, 6 Liver Unit, Policlinico Casilino Hospital, Rome, 7 Department of Internal Medicine, S. Giacomo Hospital, Rome, 8 Liver Unit, Campus Biomedico University, Rome, 9 Departments of Infectious Diseases, 1st University of Rome, Rome, 10 Department of Preventive Medicine of Migration, Tourism and Tropical Dermatology, S. Gallicano Hospital, Rome, Italy E-mail: [email protected] Background: Treatment with PEG-IFN plus RBV of HCV carriers with persistently normal ALT levels (PNALT) has been discouraged outside
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clinical trials. Only one trial (Zeuzem 2004) evaluated the efficacy of this therapy in PNALT; however, HCV-1 subjects were treated with low RBV dose (800 mg/day). Thus, the efficacy of the approved dosage of RBV (1000–1200 mg/day) has never been studied in clinical practice in patients with HCV-1 and PNALT. Simulations based on generalised additive model (GAM) analysis suggest that SVR in HCV-1 patients with PNALT significantly increases when the standard weight-adjusted dose of ribavirin is administered (Snoeck et al, 2007). Aims of this study were (i) to evaluate the overall virological responses (EoTR, SVR) to combined antiviral treatment in HCV patients with PNALT, and (ii) to evaluate whether HCV-1 patients with PNALT treated with optimal RBV dosage (1000–1200 mg/day) might achieve higher EVR than those obtained in previous RCT with lower RBV doses. Patients. 88 PNALT (53 females, range 22−60 yrs) were studied. 32 patients did harbour HCV type 1, 46 HCV-2, and 10 had HCV-3. Liver biopsy was performed in 72 patients, showing minimal fibrosis in all but 3 patients (F0−F1 Metavir). All patients received PEG interferon alfa2a 180 mg/wk plus RBV 800 mg/day for 24 wks (HCV 2 and 3 patients) or 1000–1200 mg/day for 48 wks (HCV-1 patients, according to bw). Persistent ALT normality was defined by at least 3 normal values two months apart over a 6 mo. observation period. Results: EoTR was seen in 81/88 pts (82%; 84% of HCV-1, 100% of HCV-2, 90% of HCV-3). To date, SVR has been evaluated in 63 pts (24 HCV-1 and 39 HCV-2); virological response was maintained in 37/39 HCV-2 patients (SVR 95%) and in 20/24 HCV-1 patients (83%). Side effects were not different from those observed among patients with elevated ALT levels treated in the same period. Conclusions. Antiviral treatment with PEG IFN plus RBV is safe and effective in patients with PNALT. Using standard RBV doses in patients with HCV-1, rates of SVR higher than those seen in patients with abnormal ALT can be achieved.
827 EFFICACY OF PEGINTERFERON ALPHA-2a AND RIBAVIRIN IN HIV/HCV CO-INFECTED PATIENTS: SUBANALYSIS OF HEPATYS, FRENCH NATIONAL SURVEY I. Ravaux1 , D. Ouzan2 , M. Rosenheim3 , M. Doffoel4 , P. Marcellin5 , J.M. Pawlotsky6 , C. Hayem7 , A. Pinta7 , M. Vray8 , M. Bourliere9 . 1 Infectious disease department, la Conception Hospital, Marseille, 2 Hepatology Unit, Tzank Institut, St Laurent du Var, 3 Infectious Disease Department, Piti´e-Salpˆetri`ere Hospital, Paris, 4 Hepatology Department, Civil Hospital, Strasbourg, 5 Hepatology Department, Beaujon Hospital, Clichy, 6 Virology Department, Henri Mondor Hospital, Creteil, 7 Roche, Neuilly, 8 Pasteur Institute, Paris, 9 Hepatology department, Saint-Joseph Hospital, France E-mail: [email protected] Background: In 2003, a longitudinal, multicenter prospective survey was initiated in order to assess the use and efficacy of Peginterferon alpha-2a in real life in chronic hepatitis C patients. Methods: Between November 2003 and December 2004, 334 physicians involved in C hepatitis management have included patients for whom a Peginterferon alpha-2a treatment was decided. Clinical and biological data were recorded at baseline and every three months, as well as PCR three months after the end of treatment for sustained virological response (SVR) evaluation. Results: Data from a total of 2101 patients were analyzed. Among these patients, 108 (5%) where HIV co-infected followed in hospital (87%) and in liberal practice (13%). Patients demography was as follows: mainly men (67%), mean age (±SD) 42 (±6) years, mean weight 67 (±13) Kg and 69% had a past history of injecting drug abuse. Regarding HIV infection, CD4 cells median was 407/mm3 and 84% of the patients received antiretroviral treatment. Previous or actual depression was present in 36% of the patients and an antidepressant treatment was prescribed in 26%. Almost every patient (93%, 100/108) had a liver disease evaluation, 81% (88/108) by liver biopsy. Cirrhosis was present in 23%. Genotypic
repartition was as follows: G1 48%, G2 4%, G3 35%, G4 11%, G5 1%. Majority of patients (64%) had never been treated. Higher doses of ribavirin (1000/1200 mg/day) were prescribed in 45% of the patients. SVR rates were obtained overall in 45% (37/83) and in 50% (24/48) of naive patients (36% for G1, 69% for G2,3). Patients with moderate or severe fibrosis had lower SVR rates compared to patients with minimal or no fibrosis: F0 100% (2/2), F1 67% (12/18), F2 44% (8/18) F3 42% (8/19) F4 31% (5/16). Conclusion: Efficacy of Peginterferon alpha-2a plus ribavirin used in real conditions in HIV/HCV co-infected patients is comparable to Presco trial results. 828 TREATMENT WITH PEGINTERFERON ALFA-2A (40KD) AND RIBAVIRIN IN OLDER HCV GENOTYPE 1 PATIENTS WITH POSITIVE PROGNOSTIC FACTORS LEADS TO HIGH RATES OF SUSTAINED VIROLOGICAL RESPONSE K.R. Reddy1 , D. Messinger2 , M. Popescu3 , S.J. Hadziyannis4 . 1 Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; 2 IST GmbH, Mannheim, Germany; 3 Roche, Basel, Switzerland; 4 Henry Dunant Hospital, Athens, Greece E-mail: [email protected] Background: The demographics of HCV infection are shifting, with an increasing number of patients now over 50 years of age. To assess the impact of age on sustained virological response (SVR) we analyzed the data from two large phase III studies of PEG-IFN a-2a (40KD) plus ribavirin (RBV) (NV15942 and NV15801). Methods: Patients included in this analysis were HCV genotype 1 and had received 48 weeks of treatment with PEG-IFN a-2a (40KD) 180 mg/wk plus RBV 1000/1200 mg/day. SVR was defined as undetectable HCV RNA by qualitative PCR after 24 weeks of untreated follow-up. Results: Overall, the SVR rate in patients 50 years was 52% (n = 438) and 39% in the 131 patients who were >50 years (p = 0.007). SVR rates in patients aged >50 years were heterogeneous and varied according to previously well-established prognostic factors. In particular, SVR rates were higher in older patients without advanced fibrosis (44%), those with low baseline serum HCV RNA levels (57%), those patients who received 80% of the planned dose of PEG-IFN (53%) and those patients who received 60% of the planned dose of RBV (53%). Age did not influence whether patients completed therapy (76% of patients 50 years vs. 73% of patients >50 years [p = 0.6]). However, there was a trend towards lower cumulative PEG-IFN exposure in older patients (7235 mg in patients 50 vs. 6868 mg in patients >50 years [p = 0.0986]) and a significantly lower cumulative RBV exposure in older patients (304 g in patients 50 vs. 252 g in patients >50 [p < 0.0001]). In our study more patients >50 years had dose reductions resulting in <60% of target RBV exposure than patients 50 years (38% vs. 22%). Discontinuation rates due to any AE were similar in those 50 years (11%) and those >50 years (12%). Conclusions: SVR rates in subgroups of older patients with positive prognostic factors (such as those without advanced fibrosis, low HCV RNA levels) are comparable to younger patients, especially if high rates of adherence can be maintained.