title: Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients.
abstract: The objective of this study was to find very early viral kinetic markers to predict nonresponse to hepatitis C virus (HCV) therapy in a group of human immunodeficiency virus (HIV)/HCV-coinfected patients. Twenty-six patients (15 HCV genotype-1 and 11 genotype-3) were treated with a 48-week regimen of peginterferon-alfa-2a (PEG-IFN) (180 μg/week) and weight-based ribavirin (11 mg/kg/day). Samples were collected at baseline; 4, 8, 12, 18, 24, 30, 36 and 42 h; days 2, 3, 4, 7, 8, 15, 22, 29, 43 and 57 then weekly and monthly. Five patients discontinued treatment. Seven patients (27%) achieved a sustained virological response (SVR). Nadir HCV RNA levels were observed 1.6 ± 0.3 days after initiation of therapy, followed by a 0.3- to 12.9-fold viral rebound until the administration of the second dose of PEG-IFN, which were not associated with SVR or HCV genotype. A viral decline <1.19 log for genotype-1 and <0.97 log for genotype-3, 2 days after starting therapy, had a negative predictive value (NPV) of 100% for SVR. The day 2 virological response had a similar positive predictive value for SVR as a rapid virological response at week 4. In addition, a second-phase viral decline slope (i.e., measured from day 2 to 29) <0.3 log/week had a NPV = 100% for SVR. We conclude that first-phase viral decline at day 2 and second-phase viral decline slope (<0.3 log/week) are excellent predictors of nonresponse. Further studies are needed to validate these viral kinetic parameters as early on-treatment prognosticators of nonresponse in patients with HCV and HIV.
authors.affiliation: University of São Paulo Hospital das Clínicas, Infectious Diseases Department-Hepatitis Unit, São Paulo, Brazil. evaldostanislau@uol.com.br
authors.forename: E S A
authors.initials: ES
authors.lastname: Araújo
authors.forename: H
authors.initials: H
authors.lastname: Dahari
authors.forename: A U
authors.initials: AU
authors.lastname: Neumann
authors.forename: N
authors.initials: N
authors.lastname: de Paula Cavalheiro
authors.forename: C E
authors.initials: CE
authors.lastname: Melo
authors.forename: E S
authors.initials: ES
authors.lastname: de Melo
authors.forename: T J
authors.initials: TJ
authors.lastname: Layden
authors.forename: S J
authors.initials: SJ
authors.lastname: Cotler
authors.forename: A A
authors.initials: AA
authors.lastname: Barone
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a