Guidelines for HIV/hepatitis C virus (HCV)-coinfected patients recommend HCV treatment with pegylated interferon-alfa (PEG-IFN) plus ribavirin (RBV). The adverse effects of IFN/RBV, particularly anemia, may be more common among HIV/HCV-coinfected than HCV-monoinfected patients, and are often associated with decreased health-related quality of life (HRQOL), as well as with discontinuation or dose reduction of RBV.
The HIV/HCV Coinfection Study Group evaluated the effectiveness of once-weekly epoetin alfa compared with standard of care (SOC) in correcting anemia, improving HRQOL, and minimizing RBV dose reductions in HIV/HCV-coinfected patients receiving IFN/RBV therapy.
This was a 16-week, open-label, randomized, parallel-group, multicenter study in anemic patients with HIV/HCV coinfection receiving IFN/RBV therapy for an anticipated period of >16 additional weeks. Key inclusion criteria included patient age of 18 to 75 years and hemoglobin (Hb) <12 g/dL or a >2-g/dL decrease in Hb after IFN/RBV initiation. Key exclusion criteria included a history of uncontrolled hypertension or seizure disorder, anemia attributable to another cause, and exposure to any epoetin within three months.
The primary endpoint was to compare the mean change in Hb from baseline (i.e., first dose of study drug in epoetin alfa group, day one in SOC group) to week 16 in the epoetin alfa group with that in the SOC group. Secondary endpoints were mean change in RBV dosage, HRQOL scores, physical and mental health components, and transfusion. Patients were required to complete HRQOL assessments before each visit. Safety assessments included monitoring vital signs, adverse events, alanine aminotransferase (ALT) levels, CD4 counts, HIV viral load, and HCV viral load.
- Sixty-six patients were randomized (34 to the epoetin alfa group and 32 to the SOC group). Baseline characteristics were comparable between the two groups.
- Immediately after randomization (day one/week zero), 14 patients (four epoetin alfa and 10 SOC) dropped out of the study without baseline or follow-up assessments.
- Thirty epoetin alfa patients and 22 SOC patients were included in the modified intent-to-treat (MITT) analysis.
- Twenty (63%) SOC patients and 11 (32%) epoetin alfa patients dropped out during the 16-week study period.
- Mean baseline Hb (+ standard error [SE]) was 11.1 + 0.3 g/dL in the epoetin alfa group and 11.5 + 0.3 g/dL in the SOC group (P = 0.33), and mean increases in Hb from baseline to week 16 were 2.6 + 0.3 g/dL and 0.2 + 0.3 g/dL, respectively (P<0.001).
- No patient had epoetin alfa withheld because of reaching the upper limit of Hb.
- Patients receiving epoetin alfa and zidovudine (ZDV) had a greater mean increase in Hb from baseline to week 16 than those not receiving ZDV [n = 17];
- For SOC patients, the mean change in Hb was similar in ZDV users and nonusers.
- No transfusions occurred.
- Mean RBV doses at initiation of IFN/RBV and at baseline, respectively, were 1,047 and 973 mg/d in the epoetin alfa group and 1,027 and 982 mg/d in the SOC group. At week 16, 67% of epoetin alfa patients and 45% of SOC patients were receiving RBV doses >10.6 mg/kg/d (P = 0.09).
- Epoetin alfa was well tolerated, with most adverse events mild to moderate in severity.
- Patients treated with epoetin alfa had significantly less fatigue (n = 3 [10%]) compared with those in the SOC arm (n = 9 [38%]) (P = 0.02); there was no other significant difference between groups in the incidence of common adverse events.
- Four serious adverse events were reported: one in the epoetin alfa group (constipation, which was considered unrelated to epoetin alfa) and three in the SOC group (chest pain, myocardial infarction, and psychosis).
- There were no reports of thrombovascular events or anti-erythropoietin antibodies related to epoetin alfa.
According to the authors, in this randomized study epoetin alfa effectively corrected anemia in HIV/HCV-coinfected patients treated with IFN/RBV, including those taking ZDV. The magnitude of Hb increase in coinfected patients was similar to that previously observed in IFN/RBV-related anemia in patients with HCV monoinfection.
In contrast to studies in patients with HCV monoinfection, no effect of epoetin on RBV dose was observed. A significant number of SOC patients dropped out after randomization (10 patients) and before week 16 (20 patients), however, substantially limiting our ability to assess the secondary endpoint of RBV dose, because patients and investigators may have selectively discontinued study participation in those SOC patients with worse outcomes.
Improvements in HRQOL scores were greater in patients receiving epoetin alfa, but the small sample size precluded definitive conclusions.
Editor's Note: Reprinted with permission from www.hivandhepatitis.com (first e-published July 22, 2005).
- Sulkowski MS, Dieterich DT, Bini EJ, et al; for the HIV/HCV Coinfection Study Group. Epoetin alfa once weekly improves anemia in HIV/hepatitis C virus-coinfected patients treated with interferon/ribavirin: A randomized controlled trial. J Acquir Immune Defic Syndr. 2005;39(4):504-506.