Epoetin-alfa improves interferon/ribavirin-associated anaemia

Anaemia is the most common haematologic disorder in HIV-infected patients. Combination IFN/RBV therapy for chronic HCV infection is known to induce anaemia as well; therefore, co-infected patients may be at higher risk for developing anaemia. It has been demonstrated that anaemia in HIV and HCV mono-infected patients can be treated with epoetin-alfa (EPO, Procrit). This is the first prospective, randomised study to evaluate the effect of EPO in anaemic HIV-HCV co-infected patients.

An open-label, randomised, parallel group study was conducted in 52 anaemic HIV-HCV-co-infected patients receiving IFN/RBV. Patients who had Hb ≤12 g/dL or who experienced an Hb decrease of at least 2g/dL from the start of IFN/RBV therapy were randomised to receive either EPO 40,000 IU subcutaneously once per week or no EPO (standard of care) for 16 weeks. The primary objective of this study was to evaluate the Hb response between EPO and standard of care groups at week 16.

An interim analysis was conducted in 41 patients (n = 22 [EPO], n = 19 [standard of care]). Baseline characteristics were similar between the two groups: mean age, 46.4 years; 83% men; mean weight, 80.1 kg; 10% no ARV; 90% on HAART; 54% on AZT-containing regimen; mean CD4+, 404.1 cells/µL [range 51 to 1062]. The mean duration from start of IFN/RBV therapy to randomization was 12 weeks.

The mean change in Hb from baseline to week 16 was 2.8+/-0.3 g/dL in the EPO group vs 0.4+/-0.3 g/dL in the standard of care group (p <0.001; table). AZT patients receiving EPO had a similar Hb response compared with non-AZT patients receiving EPO.

Serious adverse effects occurred in one EPO patient (constipation) and two standard of care patients (substernal chest pain, psychosis). A total of five (23%) EPO patients and seven (37%) standard of care patients dropped out within 16 weeks due to: IFN/RBV discontinuation (five EPO, three standard of care), patient request (three standard of care), lost to follow-up (one standard of care).

The authors conclude: “Anaemic HIV-HCV co-infected patients receiving IFN/RBV therapy demonstrated significant increases in Hb at week 16 with EPO compared with standard of care. Similar Hb increases have been demonstrated in HIV and HCV mono-infected patients treated with EPO.”

Comment

Erythropoietin (EPO) for ribavirin induced anemia is off label in Europe, but in the UK and Germany some doctors use it, and will try to avoid dose reductions if at all possible.

G-CSF is approved for treating leukopenia in HIV-positive patients, but this is minor issue in HCV-treatment, because severe infections are rare. There is a larger study in HCV-monoinfected patients showing a good effect on haemoglobin and a clear improvement in physical performance and QoL (AASLD 2003).

Dieterich D et al. Epoetin-Alfa administered once weekly improves anaemia in HIV-HCV co-infected patients treated with interferon/ribavirin therapy: a prospective, randomised study. 11th CROI 2004, Abstract 824 (poster).