This was a report of a randomized, double-blind, placebo-controlled study in advanced HIV infection. GM-CSF has been know to augment host immune responses. In vitro studies had found that GM-CSF increased HIV replication, but studies in humans have shown that GM-CSF decreases HIV replication (a warning about extrapolating in vivo assumptions from in vitro data!)

Patients were included who had <50 CD4 cells/mm³ or CD4 <100 cells with a previous opportunistic infection, stable antiviral therapy for at least 28 days and ANC >750 cells. Antiretroviral therapy was standard of care, chosen by the investigator. Subjects were stratified by viral load, above or below 30,000 copies/mm³.

GM-CSF was given at 250 mcg or placebo sc three times per week for 24 weeks. The investigator emphasized that this dose was not designed to augment neutrophil counts, since a much higher dose is usually used, but was, instead, intended to stimulate host immune response.

309 patients in 40 centers were studied. 70% completed 24 weeks. There was a large dropout rate and the speaker emphasized that this was not due to adverse experiences. He stated that patients either refused to start therapy or dropped out for other reasons.

Side effects were minimal. There were significantly more injection site reactions in the treatment group (25%) vs. the placebo group (4%) with a p value = 0.001. There was also more weight loss in the treatment group (18%) compared to placebo (10%), p=0.03. Both reactions were characterized as mild.

There was no decrease in clinical evolution, defined as an OI, bacterial pneumonia or death, but there was a delay in the median time to infection or death in the treatment arm.

CD4 counts were increased at every point studied in the leukine group (p=0.0004). There was no difference in viral load between the two groups.

50 patients entered the study with viral load 3. Those on GM-CSF maintained undetectable viral load better and had a delayed time to changing antiviral therapy (a change allowed by protocol).

The investigators concluded that Leukine, GM-CSF was well-tolerated and brought about a decreased time to infection or death, an increase in CD4 counts, delayed virologic breakthrough and delayed time to changing antiretroviral therapy. They suggest further studies using GM-CSF as an adjunctive therapy with HAART.