Growth Factors for Neutropenia and Anemia Effective in Coinfected Patients

Neutropenia (low white blood cell count) and anemia (low red blood cell count or low hemoglobin level) are potentially dose-limiting side effects of interferon and ribavirin, respectively. Studies in HCV-monoinfected people have shown that use of blood cell growth factors can allow maintenance of full-dose hepatitis C treatment, resulting in improved response rates. http://www.hivandhepatitis.com/2006icr/ddw/docs/060606_a.html

This prospective study assessed whether adjunct therapy with growth factors is also effective in HIV/HCV coinfected individuals. The trial included 103 coinfected patients being treated for hepatitis C for the first time with 1.5 mcg/kg/week pegylated interferon (Peg-Intron) plus 13±2 mg/kg/day ribavirin; 84% had genotype 1 HCV and 43% were African-American, a population that normally has lower average neutrophil counts compared with whites.

Participants were randomly assigned to one of two strategies to manage blood cell deficiencies:

• Reduced doses of pegylated interferon and/or ribavirin.
• Growth factor supplementation using granulocyte colony-stimulating factor (G-CSF) and/or erythropoietin alfa (EPO).

At baseline, subjects had hemoglobin levels of at least 11 g/dL (mean 14.53 g/dL) and absolute neutrophil counts (ANC) of at least 1,200 cells/mm³ (mean 2396 cells/mm³).

Patients whose hemoglobin level dropped by 3 g/dL or more, or whose hemoglobin fell to 10 g/dL or less, either had their ribavirin dose reduced to 10 mg/kg/day or received 40,000 U/week EPO. Patients whose ANC fell to 750 cells/mm³ or less either had their pegylated interferon dose reduced to 1.0 mcg/kg/week or received 5 mg/kg twice weekly G-CSF.

Results

By the fourth week on anti-HCV therapy, 44 patients (43%) had developed anemia, 20 in the dose-reduction arm and 24 in the growth factor arm. The maximal mean hemoglobin decline did not differ significantly between the two groups (3.51±1.43 g/dL vs 3.17±1.5 g/dL, respectively). The maximal mean hemoglobin increase after intervention was smaller in the dose-reduction arm compared with the growth factor group (1.7±1.05 g/dL vs 2.53±1.83 g/dL, respectively), but the difference was not statistically significant.

After two weeks, 30 patients had developed neutropenia, 17 in the dose-reduction arm and 13 in the growth factor arm. The maximal mean ANC decline also did not differ significantly between the two groups (1146.5±377 cells/mm³ vs 937.75±642.1 cells/mm³, respectively). The maximal mean ANC increase after intervention was smaller in the dose-reduction arm compared with the growth factor arm (219 ± 1031.29 cells/mm³ vs 738.38 ± 1180.65 cells/mm³, respectively), but here again, the difference was not significant.

Conclusion

The researchers concluded that “growth factor supplementation and dose reduction appear to be equally effective for the management of neutropenia and anemia in HIV/HCV coinfected individuals” treated with pegylated interferon plus ribavirin.

However, the magnitude of the increases in hemoglobin and neutrophil count after intervention suggests that growth factors might prove to be statistically superior in a larger study.

6/06/06