Background:  Positive serum HCV RNA after 6 months of pegylated interferon (peg-IFN) and ribavirin correlates with failure in HCV mono-infection. Measuring early viral decline during therapy may identify non-responders. If HCV/HIV-co-infected patients follow the same behavior remains undetermined. We compared in a group of genotypes 1/4 HCV patients, according to HIV serostatus, the sixth-month response rates, viral kinetics, and the feasibility to predict sixth-month failure measuring viral decay at week 4.

Methods:  Prospective study of 106 untreated HCV patients and genotype 1 (n = 98) or 4 (n = 8) after 24 weeks of weight-adjusted peg-IFN-α-2b and ribavirin:  group 1, 70 HCV mono-infected; group 2, 36 HCV/HIV-co-infected. HCV-RNA was measured at day 0, and weeks 4, 12, and 24. ROC curves were calculated in both groups to determine the most sensitive cutoff value of viral decay at week 4 predicting sixth-month failure. Univariate and multivariate analysis were also performed to assess baseline predictors of sixth-month failure.

Results:  Baseline HCV-RNA values were similar (5.75 vs 5.71 log₁₀, p = 0.6), but HCV mono-infected patients achieved a significantly higher rate of sixth-month response (60 vs 36%, p = 0.02), and significantly lower HCV-RNA values at weeks 4 (3.7 vs 4.1 log₁₀ , p = 0.02), 12 (2.3 vs 3.5 log₁₀ , p = 0.01) and 24 (1.4 vs 3.2 log₁₀, p = 0.001). The most sensitive cutoff values of viral decline at week 4 predicting sixth-month failure were 1 log₁₀ from baseline for group 1 (20/28, 71%; Se 100%, Sp 74%, PPV 85%, NPV 100%), ROC curve area, 0.96 (95%CI:  0.92 to 1.00) vs 0 log₁₀ (no decline or increase from baseline) for group 2 (8/23, 35%; Se 100%, Sp 83%, PPV 76%, NPV 100%), ROC curve area, 0.79 (95%CI:  0.64 to 0.95). After univariate and multivariate analysis, only HIV-co-infection was found as an independent predictor of sixth-month failure (HR 2.6, 95%CI:  1.1 to 6.0, p = 0.02). Sex, age, ALT, or HCV RNA levels, or histological severity (higher fibrosis or IAH scores, cirrhosis), did not.

Conclusions:  In HCV patients receiving peg-IFN-α-2b and ribavirin serum HCV-RNA decays at week 4 are correlated to sixth-month failure both in HCV mono-infection and HCV/HIV co-infection, and might allow early discontinuation in a significant proportion of nonresponders (71 and 35%). Significant differences in viral dynamics and cutoff values predicting nonresponse suggest a slower viral clearance in HCV/HIV co-infection. Moreover, HIV co-infection arises as an independent predictor of treatment failure.

Keywords: HCV viral Kinetics; HIV-coinfection; pegIFN/RBV