OBJECTIVES: To explore the effect of granulocyte macrophage colony stimulating factor (GM-CSF) on viral load and CD4 cell count during interruption of highly active antiretroviral therapy (HAART). METHODS: Patients on effective HAART (CD4 cell count > 400 x 10(6)/l; viral load < 50 HIV RNA copies/ml) were randomized to one of two groups: 12 weeks' treatment interruption plus, during the first 4 weeks, 300 microg GM-CSF (Leucomax-Novartis) by subcutaneous injection three times weekly (GM-CSF group); 12 weeks' scheduled treatment interruption (STI-only group). Viral load, CD4 cell count, clinical events and side effects of treatment were monitored. RESULTS: Thirty-three patients, 15 in the GM-CSF group and 18 in the STI-only group, were evaluated according to the intention-to-treat principle. The two groups were well matched with regard to pre-HAART viral loads and CD4 cell counts. During STI, viraemia was approximately two to three times lower in the group receiving GM-CSF (max 4.97 versus 5.45 in STI-only group; P = 0.03). Fifteen out of 17 patients in the STI-only group showed a decrease in their CD4 cell count between weeks 0 and 4 (median decrease 231 x 10(6) cells/l; P < 0.001); there was no such tendency in the GM-CSF group (P = non-significant when comparing CD4 cell counts at weeks 0 and 4). The median CD4 cell AUC (area under the curve) from week 0 to week 12 was higher in the GM-CSF group (9166 cells.week) than in patients without GM-CSF (7257), P = 0.02. GM-CSF produced local reactions in 88% of patients, and generalized symptoms such as fever, back pain or headache in 82% of patients. Seventy-six percent of patients 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 cell counts during a 12-weeks-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.
RCT Entities:
OBJECTIVES: To explore the effect of granulocyte macrophage colony stimulating factor (GM-CSF) on viral load and CD4 cell count during interruption of highly active antiretroviral therapy (HAART). METHODS:Patients on effective HAART (CD4 cell count > 400 x 10(6)/l; viral load < 50 HIV RNA copies/ml) were randomized to one of two groups: 12 weeks' treatment interruption plus, during the first 4 weeks, 300 microg GM-CSF (Leucomax-Novartis) by subcutaneous injection three times weekly (GM-CSF group); 12 weeks' scheduled treatment interruption (STI-only group). Viral load, CD4 cell count, clinical events and side effects of treatment were monitored. RESULTS: Thirty-three patients, 15 in the GM-CSF group and 18 in the STI-only group, were evaluated according to the intention-to-treat principle. The two groups were well matched with regard to pre-HAART viral loads and CD4 cell counts. During STI, viraemia was approximately two to three times lower in the group receiving GM-CSF (max 4.97 versus 5.45 in STI-only group; P = 0.03). Fifteen out of 17 patients in the STI-only group showed a decrease in their CD4 cell count between weeks 0 and 4 (median decrease 231 x 10(6) cells/l; P < 0.001); there was no such tendency in the GM-CSF group (P = non-significant when comparing CD4 cell counts at weeks 0 and 4). The median CD4 cell AUC (area under the curve) from week 0 to week 12 was higher in the GM-CSF group (9166 cells.week) than in patients without GM-CSF (7257), P = 0.02. GM-CSF produced local reactions in 88% of patients, and generalized symptoms such as fever, back pain or headache in 82% of patients. Seventy-six percent of patients 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 cell counts during a 12-weeks-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.
Authors: Peter Rusert; Herbert Kuster; Beda Joos; Benjamin Misselwitz; Cornelia Gujer; Christine Leemann; Marek Fischer; Gabriela Stiegler; Hermann Katinger; William C Olson; Rainer Weber; Leonardo Aceto; Huldrych F Günthard; Alexandra Trkola Journal: J Virol Date: 2005-07 Impact factor: 5.103
Authors: Xin Shi; Matthew D Sims; Michel M Hanna; Ming Xie; Peter G Gulick; Yong-Hui Zheng; Marc D Basson; Ping Zhang Journal: Int Rev Immunol Date: 2014-03-21 Impact factor: 5.311
Authors: Daniel E Kaufmann; Mathias Lichterfeld; Marcus Altfeld; Marylyn M Addo; Mary N Johnston; Paul K Lee; Bradford S Wagner; Elizabeth T Kalife; Daryld Strick; Eric S Rosenberg; Bruce D Walker Journal: PLoS Med Date: 2004-10-26 Impact factor: 11.069