A controlled trial of granulocyte macrophage-colony stimulating factor during interruption of HAART.
OBJECTIVE
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.
Fagard
Catherine
C
Divisions of Infectious Diseases, University Hospital, Geneva, Geneva, Switzerland.
Le Braz
Michelle
M
Günthard
Huldrych
H
Hirsch
Hans H
HH
Egger
Martin
M
Vernazza
Pietro
P
Bernasconi
Enos
E
Telenti
Amalio
A
Ebnöther
Corinna
C
Oxenius
Annette
A
Perneger
Thomas
T
Perrin
Luc
L
Hirschel
Bernard
B
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor