Hepatitis C virus RNA kinetics during the initial 12 weeks treatment with pegylated interferon-alpha 2a and ribavirin according to virological response.
To optimize treatment of chronic hepatitis C early identification of patients who will not achieve a sustained virological response (SVR) is desirable. We investigated hepatitis C virus (HCV) RNA kinetics at day 1 (in 15 patients; genotypes 1 and non-1, 9 and 6 respectively) at weeks 1, 4 and 12 (in 53 patients; genotypes 1 and non-1, 19 and 34, respectively) during treatment with pegylated interferon alpha-2a and ribavirin. Patients with SVR had a significantly more pronounced mean log10 decline from baseline in HCV RNA levels at weeks 1 and 4 compared with patients who failed to achieve SVR (1.99 vs 0.85 at week 1, P = 0.0003 and 2.89 vs 1.72 at week 4, P = 0.0159), whereas no difference was noted after day 1. For patients with a 2-log10 decrease in HCV RNA levels at day 7, the positive predictive value (PPV) for a SVR was 92%, whereas week 12 was the best time point for predicting a later nonresponse [negative predictive value (NPV) 92%] in patients failing to achieve a 2-log10 drop. For patients with genotype non-1 and a 2-log10 decrease in HCV RNA levels the PPV for a SVR was 89% week 1, and 79% weeks 4 and 12. The corresponding NPV for patients with genotype non-1 were 43, 40 and 100% respectively. During treatment with pegylated interferon alpha-2a plus ribavirin the HCV RNA decline at week 1 was an accurate predictor of SVR in patients who had achieved a 2-log10 drop in HCV RNA levels, whereas the lack of such decline week 12 was an accurate marker of a nonresponse.
Carlsson
T
T
Division of Infectious Diseases, Karolinska University Hospital (Solna and Huddinge), Karolinska Institutet, Stockholm, Sweden.
Reichard
O
O
Norkrans
G
G
Bläckberg
J
J
Sangfelt
P
P
Wallmark
E
E
Weiland
O
O
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014766:Viremia / Q000188:drug therapy
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