Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.
Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)
Campbell
T B
TB
University of Colorado Health Sciences Center and Bonfils Blood Center, Denver, CO 80262, USA. thomas.campbell@uchsc.edu
Sevin
A
A
Coombs
R W
RW
Peterson
G C
GC
Rosandich
M
M
Kuritzkes
D R
DR
Mladenovic
J
J
Landay
A
A
Wong
R
R
Ambruso
D
D
Miles
S
S
Pomerantz
R J
RJ
Schooley
R T
RT
D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000628:therapy; D015497:HIV-1 / Q000302:isolation & purification*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007937:Leukapheresis; D008214:Lymphocytes / Q000821:virology*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019562:Viral Load
D004279:DNA, Viral; D012367:RNA, Viral; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim