A genetically engineered drug decreases the blood transfusion requirements of some AIDS patients taking the widely used AIDS drug AZT, according to a small study published in today's New England Journal of Medicine.
The drug, recombinant human erythropoietin, stimulates the production of oxygen-carrying red blood cells. It is already available to AIDS patients under a U.S. Food and Drug Administration expanded-access program and may be approved for prescription sales later this year.
AZT therapy is increasingly recommended for AIDS patients and those with pre-AIDS conditions as a means of controlling the human immunodeficiency virus, which causes the disease.
But many patients need to receive blood transfusions or modify their use of the drug because they develop low red blood cell counts, or anemia. A drug that decreases the frequency of AZT-related anemia by stimulating the bone marrow to produce more red blood cells would ease the demand for blood transfusions and allow more patients to benefit from AZT.
Erythropoietin is cloned from a hormone of the same name that is normally present in the body. The researchers found that the AIDS patients with small amounts of erythropoietin in their blood were likely to respond to thrice-weekly injections of the drug while patients with higher concentrations were not. About three-quarters of AIDS patients have low erythropoietin levels, according to Dr. Steven Miles, a senior AIDS investigator at the UCLA Medical Center and one of the authors of the study.
"The drug works," Miles said. "It is very effective as an adjunct to specific therapy for AIDS. Patients may still have the virus and all the complications related to that but this is one less problem they have to deal with."
Miles said ongoing research suggests that advances in AIDS care have increased the potential effectiveness of erythropoietin. Patients are typically treated with lower doses of AZT, or zidovudine, than were used in the study. As a result, anemia is less likely to occur and is easier to reverse. In addition, some AIDS patients can be switched to other drugs that do not cause anemia, such as the experimental drug DDI.
Erythropoietin, marketed under the brand name Epogen by Amgen Inc. in Thousand Oaks, has been successfully used to treat the anemia associated with chronic kidney disease. But the drug is also used by athletes to enhance performance, a practice that researchers believe can be dangerous, even fatal. An excessive number of red blood cells can cause the blood of otherwise healthy people to thicken, creating a risk of strokes and heart attacks.
The study was funded by the Ortho Pharmaceutical Corp. of Raritan, N.J., which has approval from the U.S. Food and Drug Administration to develop erythropoietin as an AIDS-related therapy.
Ortho has not yet said how much its erythropoietin will cost. But if Ortho's charges for a vial of medication are similar to Amgen's, a year's supply for an AIDS patient will cost about $4,000, Miles said.
For reasons that are not well understood, AIDS patients taking AZT have widely varying concentrations of erythropoietin in their bloodstreams.
During the three-month study, 29 patients received erythropoietin injections and 34 received placebo injections.
At the beginning of the study, the AIDS patients with low erythropoietin levels required an average of about 1.5 units of blood a month. At the end of the study, those receiving erythropoietin required an average of 0.84 units of blood a month, while those receiving the placebo required an average of 2.74 units of blood a month.
By comparison, at the beginning of the study the AIDS patients with high erythropoietin levels required an average of about 3.2 units of blood a month. At the end of the study, those receiving erythropoietin required an average of 3.5 units of blood a month, while those receiving the placebo required 2.78 units of blood a month. These differences were not statistically significant.