OBJECTIVE It is not known whether the probability of achieving sustained virological response (SVR) can be determined on the basis of the magnitude of HCV viral decline over the first 4 weeks of Peg-IFN/RBV treatment of HIV/HCV co-infected patients who fail to achieve a rapid virological response (RVR). METHODS HIV patients co-infected with HCV genotype 1 naïve to Peg-IFN/RBV treatment were included. HCV viral decline from baseline to week 4 was graded. The positive predictive value (PPV) for SVR was evaluated according to the magnitude of HCV viral decline at week 4. RESULTS One hundred and fifty patients were included. Thirty-four (22.6%) patients achieved RVR, 33 of these (PPV [CI 95%]; 97.05% [86.34-99.85]) achieved SVR. In those patients who did not achieve RVR, the probability to achieving SVR was graded according to the magnitude of viral decline at week 4 (>2 log10 [55.5%], >2.5 log10 [73.3%] and >3 log10 [75%]). The combination of undetectable and magnitude of decline (>2.5 log10) had a PPV for SVR of 89.8% (CI 95%; 0.794-0.964). CONCLUSIONS The combination of undetectable HCV viral load and magnitude of decline at week 4 has a high PPV for SVR and identified a higher number of potential Peg-IFN/RBV responders.