Bone marrow transplant drug helps suppress HIV
September 1, 1999 3 minutes read
Bone marrow transplant drug helps suppress HIV
Research to be presented at ICAAC conference
A drug used in bone marrow and stem cell transplantation has shown promising results in blocking HIV when it’s used in conjunction with other antiretroviral medications.
Sargramostim or GM-CSF (Leukine), manufactured by Immunex in Seattle, has been approved by the U.S. Food and Drug Administration (FDA) for use in bone marrow transplant treatment and for treatment of chemotherapy-induced neutropenia in older adults with acute myelogenous leukemia. The FDA has not yet approved sargramostim for use in treating HIV/AIDS.
However, recent studies have demonstrated that sargramostim, administered through injections three times per week, helps block HIV entry into immune system cells. It also reduces the development of HIV resistance to AZT, and it stimulates immune system cells necessary to fight infections.
Drug helps maintain HIV suppression
"Once you’ve achieved suppression with drugs, it helps to maintain that," says Jonathan Angel, MD, a lead investigator in the sargramostim and HIV studies and an assistant professor of medicine at the University of Ottawa in Canada. Angel, who also is an infectious disease specialist at Ottawa General Hospital in Ontario, will be presenting research about sargramostim and HIV at the Interscience Conference on Antimicrobial Agents and Chemotherapy, to be held Sept. 26-29 in San Francisco.
"It’s an adjunct therapy to good antiretroviral therapy," Angel adds. "Since antiretroviral therapy fails in many patients, whatever you can add to enhance its ability or prolong its activity or increase its durability is helpful."
The 309-patient phase III sargramostim trial was double-blinded, randomized, and placebo-controlled. The study evaluated the drug’s impact on the incidence of opportunistic infections, the rate of survival, and changes in viral load and CD4 cell counts. The trial divided patients in two groups: those with viral loads below 30,000 copies/mL, and those with viral loads above that level. The study found that of the 115 patients with viral loads lower than 30,000 copies/mL, 81% of the patients receiving sargramostim were able to remain on the same antiretroviral regimen and maintain their baseline level of viral suppression throughout the six-month study. This compared with 62% of the patients receiving placebo maintaining a baseline level of viral suppression.
The same research, however, did not show evidence that sargramostim reduced the incidence of opportunistic infections, bacterial pneumonia, or death. But it did reduce the incidence of all infections, Angel says.
"The study started around the time protease inhibitors were being used, and because of protease inhibitors, there were fewer opportunistic infections anticipated, and that’s one reason we didn’t see fewer opportunistic infections," he explains.
"But if we looked at all infections, including sinusitis, skin infections, and IV-line related infections, there was a decrease in the number, and the infections were less severe, and there was greater delay before the development of infections," he adds.
Trial reveals CD4 increase
A phase I trial, conducted on 20 HIV patients with CD4 cell counts of 10 to 590 and who were on therapies that included ritonavir or indinavir, gave patients either sargramostim or a placebo for eight weeks. During the study, which included four weeks of follow-up, eight of 10 patients receiving sargramostim had an increase of 30% or more in CD4 cell counts, as compared to three of 10 patients receiving a placebo.
A double-blinded, randomized study of 105 patients in Brazil compared the effects of sargramostim in combination with AZT or AZT plus another nucleoside analog to that of a placebo with the additional drugs. All patients had CD4 cell counts of less than 300. At the end of six months, sargramostim reduced mean viral load by -.74 log10 or 69% as compared to -0.11 log10 or 2% in the placebo group. Sargramostim also increased CD4 cell counts by more than 30% in 80% of the patients, while 58% of those in the placebo group experienced a 30% increase. Further, a genotypic analysis showed that sargramostim retarded the development of resistance to AZT.
Sargramostim is well-tolerated by patients, Angel says. The most significant side effects were mild injection site reactions (requiring no treatment) and mild weight loss.
"From our study, there are not any significant risks associated with the drug other than its cost and inconvenience of patients having to take injections," Angel says.
The main drawback to physicians prescribing sargramostim is that, at present, it would be an off-label drug for HIV patients in the United States, and thus would not be reimbursed by payers. The drug is not available in Canada because there are no distributors for it.
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