653 Granulocyte Macrophage-colony Stimulating Factor Blunts Viral Rebound during Interruption of HAART C. Fagard1, H. F. Günthard2, H. H. Hirsch3, M. Egger4, P. Vernazza5, E. Bernasconi6, A. Telenti7, M. Le Braz1, L. Perrin1, B. Hirschel*1, Swiss HIV Cohort8 1Univ Hosp, Geneva, Switzerland; 2Univ Hosp, Zurich, Switzerland; 3Univ Hosp, Basel, Switzerland; 4Inselspital, Berne, Switzerland; 5Univ Hosp, St Gallen, Switzerland; 6Hosp Civico, Lugano, Switzerland; 7CHUV Lausanne, Switzerland; and 8
Background: To explore the effect of granulocyte macrophage-colony stimulating factor (GM-CSF) on viral load and CD4 count during interruption of highly active antiretroviral therapy (HAART).
Methods: Patients (pts) on effective HAART (CD4 cells > 400 per ml, viral load < 50 copies/ml) were randomized to 1 of 2 groups: 1) 12 wks treatment interruption plus, during the first 4 wks, 300 micrograms of GM-CSF (Leucomax) by subcutaneous injection 3 times weekly (GM-CSF group), and 2) 12 wks scheduled treatment interruption (STI-only group). Viral load, CD4 count, clinical events, and side-effects of treatment were monitored.
Results: Thirty-three (33) pts, 15 in the GM-CSF group and 18 in the STI-only group, were evaluated according to the intention-to-treat principle. The 2 groups were well matched with regard to pre-HAART viral loads and CD4 counts. During STI, viremia was approximately 2 to 3 times lower in the group receiving GM-CSF; this difference reached statistical significance at wks 6 and 10 without treatment (p < 0.04). Fifteen (15) of 17 pts in the STI-only group showed a decrease in their CD4 count between wks 0 and 4 (median decrease 231 cells/mm3, p < 0.001); there was no such tendency in the GM-CSF group (p = NS when comparing CD4 counts at wk 0 and 4).
GM-CSF produced local reactions in 88 percent of pts, and generalized symptoms such as fever, back pain, or headache in 82 percent of pts. Seventy-six percent (76%) of pts completed the planned course of 12 injections.
Conclusions: The administration of GM-CSF blunted the viral rebound following interruption of HAART, and largely prevented a decrease of CD4 counts during a 12 wks treatment interruption. A better understanding of the underlying mechanism(s) may help to identify synergistic treatment targets and improved administration protocols to enhance control of chronic HIV infection.
