December 16, 2001
Anemia is the most frequent blood-related complication in people living with HIV disease. Anemia can cause symptoms of fatigue, including weakness, exercise intolerance, shortness of breath, rapid heart rate, and mental slowing, all symptoms that impair day-to-day functioning and quality of life.
As the use of highly active antiretroviral therapy (HAART) has improved the overall health of patients with HIV, anemia has been perceived as a less important clinical issue. However, anemia remains a very real problem for patients, particularly those with advanced disease who are least able to cope with additional physical setbacks. Anemia also has a detrimental impact on the progression of HIV disease. An inverse relationship exists between anemia and survival among patients with HIV. Recently, it has been shown that HIV-positive patients who recovered from anemia had a significant longer survival time compared to those who remained anemic.
Recombinant human erythropoietin (epoetin alpha, Procrit) is both biologically and immunologically indistinguishable from naturally occurring erythropoietin. This substance stimulates the production of new red blood cells in the bone marrow.
The safety and efficacy of procrit have been well established in a variety of clinical trials, and, over the past decade, it has been used in over one million patients in the U.S.
The thrice-weekly dosing schedule in anemic HIV-positive patients receiving zidovudine (AZT) has been shown to correct the anemia, decrease blood transfusion requirements, and improve quality of life. Once-weekly procrit (40,000 units) has been shown to be similar to thrice-weekly dosing (150 IU/kg) in increasing hemoglobin and improving quality of life in cancer patients receiving chemotherapy.
The present study compared the effect of QW (once-weekly) versus TIW (thrice-weekly) administration of procrit on hemoglobin levels and quality of life (QOL) in HIV-positive patients receiving antiretroviral therapy. The study was done to see if the more convenient once-weekly dosing schedule was as effective as the thrice-weekly schedule.
The present study is similar in design to a study done by the CHAMPS study group and presented at the 39th Annual Meeting of the Infectious Diseases Society of America in October 2001.(1) Michael Saag, M.D. et al. in the CHAMPS study showed that once-weekly dosing for 16 weeks increased hemoglobin by at least 1 g/dL in 75% of the patients with a mean rise in hemoglobin of 2.7 g/dL.
The once-weekly procrit-dosing schedule was found to be efficacious in HIV-positive patients on antiretroviral therapy with or without AZT and across all races. Procrit increased hemoglobin levels independent of baseline CD4 cell count, viral load, and change in CD4 cell count, indicating its effects are independent of these parameters. As the hemoglobin increased, quality of life improved proportionately in a statistically significant fashion. The maximum increase in quality of life parameters occurred when the hemoglobin was increased to 10-12 g/dL.
In the present study, Dr. Grossman and colleagues report an interim analysis of 174 anemic (hemoglobin < 12 g/dL) HIV-positive patients randomized to receive procrit either once weekly or thrice weekly.
Improvement in hemoglobin levels and quality of life were found to be similar for both dosing regimens with no statistically significant differences noted. This randomized prospective open-label study provided a direct comparison of therapeutic efficacy and tolerability of once-weekly versus thrice-weekly administration of procrit in anemic HIV-positive patients. The mean increase in hemoglobin was 2.4 g/dL in the TIW group and 2.8 g/dL in the QW group. These results clearly indicate that, as in the CHAMPS study, the more convenient once-weekly dosing schedule is equally effective as thrice-weekly in increasing hemoglobin levels and improving quality of life. Both once-weekly and thrice-weekly administration of procrit was found to be safe and well tolerated.
Taken together, these two studies in HIV-positive anemic patients, coupled with similar findings in anemic cancer patients receiving chemotherapy, indicate that the convenient once-weekly dosing of procrit is comparable to thrice-weekly dosing in:
in patients with HIV, regardless of AZT use, CD4 cell count, or plasma viral load.
The importance of this study for both physicians and patients is that it provides further evidence of the efficacy and safety of the more convenient once-weekly dosing schedule. Further, the study suggests that the effect is seen independent of the use of AZT or prognostic markers such as CD4 cell count or plasma viral load.
Dosing convenience has frequently been linked to adherence and consequently this more convenient, equally efficacious regimen would be expected to improve compliance. Medication regimens for patients with HIV disease are frequently complex and rigorous. Any improvement in dosing convenience would be warmly welcomed by both prescribing physicians and people living with HIV.