Ultra Rapid Virological Response at Week 2 Predicts Sustained Response in HCV Genotype 3 Patients with High Viral Load: The Get-C Study

Response to interferon-based therapy for hepatitis C early in the course of treatment can help predict which patients will achieve sustained response over the long term. Researchers are interested in predicting in advance which patients will respond, in order to spare likely non-responders the side effects and cost of additional futile treatment.

The aim of the current study, presented at the 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007) in Boston (November 2-6, 2007), was to assess the impact of HCV viral clearance at week 2 of therapy on the sustained virological response (SVR) rate of HCV genotype 3 patients with a high viral load.

The GET-C study is an ongoing study designed to evaluate extended therapy in genotype 3 patients with a high baseline viral load > 400,000 IU/ml. Patients were randomized to receive 1.5 mcg/kg/week pegylated interferon alfa 2b (PegIntron) plus weight-based ribavirin for 24 or 48 weeks.

The Australian investigators assessed the predictive value of week 2 and week 4 response for SVR. Viral load was determined using the Versant HCV RNA 3.0 bDNA assay (Bayer Diagnostics) (limit of detection 615 IU/ml) at baseline and at weeks 2, 4, 12, 24, 36, 48, and 72 (if applicable). Statistical analysis was performed using the Fisher's Exact Chi Square two-tailed test.

Results

• Baseline demographics were similar in treatment responders and non-responders.

• Of the first 43 patients who have completed therapy and follow up, 42 had week 2 virological data available.

• Of these 42 patients, 30 (71%) achieved viral suppression to below 615 IU/ml at week 2.

• Of these, 28 had a SVR, for a positive predictive value (PPV) of 93%.

• 12 patients did not clear the virus by week 2.

• Of these, 5 did not achieve a SVR, for a negative predictive value (NPV) of 42%.

• The impact on SVR of achieving a viral load reduction to < 615 IU/ml at week 2 was statistically significant (P = 0.011).

• Of 42 patients, 39 (93%) had a viral load below 615 IU/ml at week 4.

• 7 patients who were HCV positive at week 2 were negative at week 4 and 4 or the 7 achieved a SVR (57%).

Conclusion

The authors concluded, "An ultra rapid virological response at week 2 was highly predictive of SVR (PPV 93%). The data in 42 genotype 3 patients with high viral load suggest that week 2 may be a useful time for predicting SVR."

Further, they wrote, "Patients who fail to attain an undetectable viral load by week 2 have a significantly reduced chance of achieving a SVR and may benefit from extended therapy, which is being evaluated in the GET-C study."

Gastroenterology Department, Monash Medical Centre, Melbourne, VIC, Australia; Auckland Hospital, Auckland, New Zealand; Royal Adelaide Hospital, Adelaide, SA, Australia; VIDRL, Melbourne, VIC, Australia; Schering Plough Pty Ltd, Sydney, NSW, Australia.

11/09/07

Reference
S Pianko, W Sievert, E Gane, and others. Ultra Rapid Virologic Response Predicts Sustained Virologic Response in HCV Infected Patients with Genotype 3 and High Viral Load: The Get-C Study. 58th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2007). Boston, MA. November 2-6, 2007. Abstract (poster) 349.