HCV Load Decay in First Day of PegIFN Treatment Predicts Long-Term Failure

HCV Load Decay in First Day of PegIFN Treatment Predicts Long-Term Failure

49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy), September 12-15, 2009, San Francisco

Mark Mascolini

In a small study of people coinfected with HIV and hepatitis C virus (HCV), no one who failed to attain at least a 0.9-log drop in HCV load during the first 24 hours of pegylated interferon (PegIFN) plus ribavirin had a sustained virologic response (SVR) after completing treatment [1], or "Patients who do not reach 0.9 log decay at 24 hours will not achieve SVR". Pedro Cahn and colleagues at the Argentinean Reference Center for AIDS in Buenos Aires suggest that this cutoff may prove valuable in guiding treatment of HCV infection in people with HIV, especially in resource-poor settings. But results of this 20-person, single-center study require confirmation in larger, more diverse populations.

Up to 60% of HIV/HCV-coinfected people fail to respond to PegIFN/ribavirin, especially those with HCV genotypes 1 and 4 (from Jules: in a study but in the clinic coinfected genotype 1 patients often do much worse than 40% SVR, sometimes 15-20% SVR). To ascertain the impact of HCV dynamics on SVR, Cahn and coworkers collected HCV samples from 20 coinfected people before they started PegIFN/ribavirin, 24 hours after they started, and 4, 12, 24, 48, and 72 weeks after they started.

Nineteen of the 20 patients were taking antiretroviral therapy, 17 were men, 15 had HCV genotype 1, 10 had a Metavir score of F3-F4 (bridging fibrosis to cirrhosis), and CD4 count averaged 545.

HCV load at 24 hours was significantly greater in people with SVR than in those without SVR (1.6 +/- 0.2 versus 0.5 +/- 0.4 log). Receiver operating characteristic (ROC) curve analysis determined that a 0.9-log HCV decay was the best cutoff to discriminate between sustained virologic responders and nonresponders.

That cutoff had a 100% negative predictive value for SVR (95% confidence interval [CI] 66.2% to 100%), meaning no one without at least a 0.9-log decay in 24 hours reached an SVR. Positive predictive value of the 0.9-log cutoff was 71.4% (95% CI 29.3% to 95.5%). Sensitivity of the 0.9-log cutoff in predicting SVR was 100% (95% CI 48% to 100%) and specificity 81.8% (95% CI 48.2% to 97.2%).

Cahn and colleagues suggest that the 0.9-log 24-hour response cutoff could be particularly helpful in patients with other predictors of poor response or with a high risk of toxicity from PegIFN/ribavirin.

Reference
1. Laufer N, Bolcic F, Socias E, et al. Early changes in HCV viral load during the first 24 hours of treatment exhibit a very high negative predictive value of sustained virological response in HCV/HIV coinfected patients. 49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy). September 12-15, 2009. San Francisco. Abstract H-213.