Background:  Anemia is the most frequent and limiting side effect of ribavirin (RBV) in the treatment of chronic hepatitis C virus (HCV) infection. In HIV/HCV-co-infected patients, the use of zidovudine (AZT) may further increase the risk of anemia. The effect of anemia and AZT use on anti-HCV treatment success has not been well characterized.

Methods:  PRESCO was a multi-center, prospective trial conducted in Spain that evaluated the efficacy and safety of pegylated interferon-alpha2a (pegIFN-a2a) (Pegasys) 180 µg/week plus ribavirin (RBV) 1000 (if body weight <75 kg), 1200 (if body weight ³75 kg) mg/day as treatment of chronic hepatitis C in HIV⁺ subjects with CD4 counts >300 cells/µL. Only patients achieving >2 log drop in HCV RNA at week 12 were allowed to continue on therapy. It lasted for 6 or 12 months in HCV genotypes 2 and 3, and 12 or 18 months in HCV-1 and -4. Severe anemia was defined as a drop in hemoglobin (Hb) levels below 8 g/dL.

Results:  We included 389 patients in the trial (49% HCV-1, 39% HCV-2/3, and 12% HCV-4) of whom 74% were male and on HAART 74. Median age was 40 years; median CD4 = 546 cells/mm³; median baseline Hb levels = 15.5 g/dL. In an intent-to-treat analysis, sustained virological response was achieved in 193 (49%). Severe anemia, either isolated or in the setting of pancytopenia, occurred in 13 (3.3%) patients, but was significantly more frequent in patients taking AZT concomitantly (7 of 85; 8.2%) than in the rest (6 of 304; 2%) (p = 0.01). Premature discontinuations due to severe anemia tended to be more frequent when AZT was co-administered, although differences did not achieve statistical significance:  4 of 85 (4.7%) vs 5 of 304 (1.6%) (p = 0.09). Reductions of RBV dose were significantly more frequently needed among patients taking AZT (25/85; 29.4%) than among the remaining (59 of 304; 19.4%) (p = 0.048). Epoetin was administered to only 1 patient. Interestingly, no association between development of severe anemia, use of AZT or reduction of RBV dosage, and achievement of sustained virological response could be demonstrated.

Conclusions:  Severe anemia was infrequent and did not impact on the achievement of sustained virological response in this trial, which is the largest conducted so far in HIV/HCV-co-infected patients treated with pegIFN+RBV. The use of AZT was associated with higher incidence of severe anemia and more frequent RBV dose reductions. Given the availability of other nucleoside analogues, avoidance of AZT during HCV treatment should be advised.