Treatment of Anemia with Aranesp® (Darbepoetin-alfa) Given Once Every Two Weeks in HIV Seropositive Patients.

Background: Anemia is common in patients (pts) infected with the Human Immunodeficiency Virus (HIV). In these pts, anemia is associated with diminished quality of life (QoL) and is an independent prognostic factor for mortality. Aranesp^® (darbepoetin-alfa) is a recombinant erythropoiesis-stimulating protein with extended serum half-life allowing for less frequent dosing than conventional recombinant erythropoietin. We studied Aranesp^® in anemic HIV-positive pts to evaluate safety, hemoglobin (Hgb) response, and quality of life (QoL).

Methods: Entry criteria included HIV infection, Hgb < 11.5 g/dL, and adequate renal and liver function. Patients with anemia due to bleeding, malignancy, B12, folate, or iron deficiency were excluded. Aranesp^® 3.0 mg/kg was given sc every 2 weeks (Q2W) for 24 weeks. Treatment response was defined as Hgb increase of ≥ 1.5 g/dL from baseline sustained for ≥ 4 weeks duration at any time during the study. If no response by wk 8, Aranesp^® was escalated to 5.0 μg/kg.

Results: Thirteen female and 10 male pts have been enrolled to date. Median age was 43 years (range 27–67), median entry Hgb was 10.6 g/dL (range 8.6–11.5), and median CD4 count was 197 cells/mm³ (range 29–821). Nine (39%) pts had a prior clinical AIDS-defining illness or opportunistic infection, 19 (87%) pts received concurrent HAART therapy; 11 (58%) were receiving a zidovudine- containing regimen with either combivir (n=6) or trizivir (n=5). Aranesp^® was well tolerated. The only treatment-associated side effect was mild pain at the injection site. Pts who received ≥ 8 wks of Aranesp^® were analyzed (n=20). 17 of the 20 pts (85%) had a Hgb response (median duration 12+ weeks [range 4+ to 22+]). One of these pts required a dose escalation. Evaluation of change in QoL using a Linear Analog Scale in 20 evaluable patients showed a mean improvement in energy level (+23.2 mm), activity level (+19.8 mm) and overall QoL (+15.5 mm) over the first 8 wks of treatment.

Conclusions: In HIV-infected pts with anemia, Aranesp^® at a dose of 3.0 mg/kg Q2W is well tolerated, is associated with a Hgb response in the majority of pts, effectively maintains Hgb levels, and improves QoL. Further work is on-going.