Influence of HCV genotype 1 subtypes on the virus response to PEG interferon alpha-2a plus ribavirin therapy.
New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (RBV; 800-1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31-76) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR=  2.98, 95% CI: 1.15-7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31-8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7-26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4-97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.
CHU Toulouse, IFB Purpan, Laboratoire de Virologie, Toulouse, France.
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F
Nicot
L
L
Alric
K
K
Barange
S
S
Métivier
J M
JM
Dramard
J M
JM
Combis
B
B
Castan
J J
JJ
Meurisse
J L
JL
Payen
D
D
Garipuy
H
H
Desmorat
J M
JM
Peron
S
S
Thebault
T
T
Morin
C
C
Renou
P
P
Barel
B
B
Guerin
Y
Y
Imbert
S
S
Sire
K
K
Sauné
E
E
Chatelut
J
J
Izopet
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000821:virology; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000097:blood / Q000627:therapeutic use; D012254:Ribavirin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a