title: Viral kinetics and early prediction of nonresponse to peg-IFN-alpha-2b plus ribavirin in HCV genotypes 1/4 according to HIV serostatus.
abstract: To evaluate, among 70 hepatitis C virus (HCV)-monoinfected and 36 human immunodeficiency virus (HIV)-coinfected naïve patients with genotypes 1/4 receiving weight-adjusted pegylated interferon-alpha-2b/ribavirin, viral kinetics and the feasibility to predict treatment failure measuring early HCV-RNA decreases. HCV-RNA was assessed at baseline, weeks 4, 12 and 24. Receiver operating characteristic (ROC) curves were calculated to determine the most sensitive cut-off values of viral decrease at week 4 predicting treatment failure. Baseline predictors of failure were evaluated by univariate and multivariate analyses. Despite similar baseline HCV-RNA (5.75 vs 5.72 log(10)IU/ml, P = 0.6), HCV monoinfection led to significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.3 log(10)IU/ml, P = 0.01), 12 (2.3 vs 3.5 log(10)IU/ml, P = 0.01) and 24 (1.4 vs 3.3 log(10)IU/ml, P = 0.001) and a higher rates of viral clearance at weeks 24 (60%vs 36%, P = 0.02), 48 (46%vs 25%, P = 0.03) and 72 (37%vs 17%). The lack of achieving an HCV-RNA decrease of at least 1 log(10) at week 4 was highly predictive of treatment failure for HCV-monoinfected patients (Se 100%, Sp 50%, positive predictive value (PPV) 57%, negative predictive value (NPV) 100%, ROC curve area, 0.86 [95% confidence interval (CI) 0.77-0.95], but not for HCV/HIV-coinfected patients (cut-off, 0 log(10), Se 100%, Sp 27%, PPV 21%, NPV 100%, ROC curve area, 0.71 (95% CI 0.49-0.93). HIV coinfection was independently associated with failure (odds ratio 2.95, 95% CI 1.08-8.04, P = 0.01). Thus the magnitude of HCV-RNA decreases at week 4 correlated with treatment response. Significant differences in viral kinetics and cut-off values predicting nonresponse suggest a slower HCV clearance rate in HIV coinfection, which was independently associated with treatment failure.
authors.affiliation: Service of Infectious Diseases, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain. amoreno.hrc@salud.madrid.org
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: R
authors.initials: R
authors.lastname: Bárcena
authors.forename: S
authors.initials: S
authors.lastname: García-Garzón
authors.forename: L
authors.initials: L
authors.lastname: Moreno
authors.forename: C
authors.initials: C
authors.lastname: Quereda
authors.forename: A
authors.initials: A
authors.lastname: Muriel
authors.forename: J
authors.initials: J
authors.lastname: Zamora
authors.forename: M L
authors.initials: ML
authors.lastname: Mateos
authors.forename: M J
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: A
authors.initials: A
authors.lastname: Antela
authors.forename: S
authors.initials: S
authors.lastname: Diz
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: S
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006678:HIV / Q000276:immunology; D006679:HIV Seropositivity / Q000378:metabolism / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011446:Prospective Studies; D012367:RNA, Viral / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b