Filgrastim seems to increase survival in AIDS patients but the mechanism remains unclear

Granulocyte colony-stimulating factor therapy in patients with AIDS-related cytomegalovirus (CMV) retinitis is associated with a 56% reduction in mortality, according to a recent report. However, the reason for this survival benefit does not appear to involve a reduction in bacterial infections.

Prior to the advent of highly active antiretroviral therapy (HAART), neutropenia was a relatively common finding in patients with AIDS, study author Dr Douglas A Jabs, from the Johns Hopkins University in Baltimore, and colleagues note in the March 29th issue of AIDS

Because neutropenia is an established risk factor for bacterial infection, the authors hypothesised that treatment with filgrastim — granulocyte colony-stimulating factor, which reverses neutropenia — might prevent such infections and thereby improve survival.

To investigate, the researchers retrospectively studied 709 patients with AIDS-related CMV retinitis who were treated between 1990 and 1997. Of these patients, 398 had used filgrastim at some point.

Filgrastim use was associated with a significant reduction in the risks of catheter-related bacteremia and repeat bacterial infection (p = 0.02 and < 0.01, respectively), Dr Jabs and colleagues found.

However, after adjustment for CD4+ T-cell count and antibiotic/antiretroviral therapy, filgrastim therapy was no longer linked to a significant reduction in these risks. The authors believe this may have been due to the confounding effect of trimethoprim-sulfamethoxazole use.

Despite no clear effect on bacterial infections, filgrastim use was tied to a 56% reduction in mortality (p < 0.001), the researchers state.

“Our observation of a large survival benefit with the use of filgrastim, while unexplained by a reversal of neutropenia or reduction of infection, deserves further exploration in a randomised controlled trial of this cytokine in non-neutropenic AIDS patients receiving HAART,” Dr Jab’s team concludes.

Comment

Similar benefits in advanced disease have also been reported for the immunotherapy agents GM-CSF (molgramostim) and gamma interferon.

Upregulation of phagocytic responses to pathogens may be one mechanism of action as well as improved antigen presentation and perhaps increased IL-2 receptor expression.