Comparison of High Ribavirin Induction Versus Standard Ribavirin Dosing, Plus Peginterferon-alpha for the Treatment of Chronic Hepatitis C in HIV-Infected Patients: The PERICO Trial
Por:
Labarga, P, Barreiro, P, da Silva, A, Guardiola, JM, Rubio, R, Aguirrebengoa, K, Miralles, P, Portu, J, Tellez, MJ, Morano, L, Castro, A, Pineda, JA, Terron, A, Hernandez-Quero, J, Marino, A, Rios, MJ, Echeverria, S, Asensi, V, Vispo, E, Soriano, V
Publicada:
15 sep 2012
Resumen:
Background. Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection.
Methods. HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-alpha-2a (180 mu g/d) plus either RBV standard dosing (1000 or 1200 mg/d if < 75 or >= 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin beta (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response.
Results. A total of 357 patients received >= 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 mu g/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR.
Conclusions. A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.
Filiaciones:
Labarga, P:
Hosp Carlos III, Madrid 28029, Spain
Barreiro, P:
Hosp Carlos III, Madrid 28029, Spain
da Silva, A:
Hosp Xeral Cies CHUVI, Vigo, Spain
Guardiola, JM:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Rubio, R:
Hosp 12 Octubre, E-28041 Madrid, Spain
Aguirrebengoa, K:
Hosp Cruces, Bilbao, Spain
Miralles, P:
Hosp Gen Gregorio Maranon, Madrid, Spain
Portu, J:
Hosp Txagorritxu, Vitoria, Spain
Tellez, MJ:
Hosp Clin San Carlos, Madrid, Spain
Morano, L:
Hosp Meixoeiro CHUVI, Vigo, Spain
Castro, A:
CHUAC, Coruna, Spain
Pineda, JA:
Hosp Valme, Seville, Spain
Terron, A:
Hosp Jerez, Jerez de la Frontera, Spain
Hernandez-Quero, J:
Hosp Clin San Cecilio, Granada, Spain
Marino, A:
Hosp Arquitecto Marcide, Ferrol, Spain
Rios, MJ:
Hosp Virgen de la Macarena, Seville, Spain
Echeverria, S:
Hosp Marques de Valdecilla, Santander, Spain
Asensi, V:
Hosp Cent Asturias, Asturias, Spain
Vispo, E:
Hosp Carlos III, Madrid 28029, Spain
Soriano, V:
Hosp Carlos III, Madrid 28029, Spain
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