title: A controlled trial of granulocyte macrophage-colony stimulating factor during interruption of HAART.
abstract: 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.
authors.affiliation: Divisions of Infectious Diseases, University Hospital, Geneva, Geneva, Switzerland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.forename: Michelle
authors.initials: M
authors.lastname: Le Braz
authors.forename: Huldrych
authors.initials: H
authors.lastname: Günthard
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Martin
authors.initials: M
authors.lastname: Egger
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Corinna
authors.initials: C
authors.lastname: Ebnöther
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
authors.forename: Thomas
authors.initials: T
authors.lastname: Perneger
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
mesh_terms: 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
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor