Labarga, PabloBarreiro, PabloSilva, Alfredo daGuardiola, Josep MaríaRubio, RafaelAguirrebengoa, KoldoMiralles, PilarPortu, JosebaTéllez, María JesúsMorano, LuisCastro-Iglesias, ÁngelesPineda, Juan A.Terrón, AlbertoHernández-Quero, JoséMariño, AnaRíos, María JoséEcheverría, SantiagoAsensi, VíctorVispo, EugeniaSoriano, Vicente2019-01-212019-01-212012-07-17Labraga P, Barreiro P, da Silva A, et al. Comparison of High Ribavirin Induction Versus Standard Ribavirin Dosing, Plus Peginterferon-α for the Treatment of Chronic Hepatitis C in HIV-Infected Patients: The PERICO Trial. J Infect Dis. 2012; 206(6): 961-9680022-1899http://hdl.handle.net/2183/21607[Abstract] 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-α-2a (180 μg/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 β (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 μg/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.engThis is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Infectiuos Diseases following peer review. The version of record is avaliable online at Oxford Academic web.Antiretroviral therapy highly activeAntiviral agentsDose-Response relationshipDrug therapy-CombinationHIV infectionHepacivirusHepatitis CInterferon-alphaPolyethylene glycolsRNA viralRecombinant proteinsRibavirinjournal articleopen access