Increased replication of HIV-1 minor variants during hematopoietic stem-cell mobilization with filgrastim.
The hypothesis that filgrastim (r-met-huG-CSF) activates replication of minor variants of human inmmunodeficiency virus type 1 (HIV-1) was tested by analysis of plasma quasi-species composition in 7 subjects in whom plasma HIV-1 RNA had increased during filgrastim treatment. Inferred phylogenetic trees of env sequences from 3 subjects during filgrastim treatment contained unique intrasubject subclusters that shared a most recent common ancestor with the baseline HIV-1 quasi species. Genotypes in the unique subclusters were not detected before filgrastim treatment, yet they composed 40%-70% of the plasma quasi species during treatment. The minority variants that appeared in 1 subject were more distantly related to plasma quasi species present 5 years before filgrastim treatment than were the majority of the pretreatment plasma quasi species. These findings provide evidence that increased HIV-1 replication during filgrastim treatment was associated with activation of HIV-1 variants that, before filgrastim treatment, were minor components of the plasma quasi species.
Campbell
Thomas B
TB
Division of Infectious Diseases, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA. thomas.campbell@uchsc.edu
Rapaport
Eric
E
Schooley
Robert T
RT
Kuritzkes
Daniel R
DR
D000595:Amino Acid Sequence; D024882:Drug Resistance, Viral / Q000235:genetics; D000069585:Filgrastim; D015752:Genes, env; D014644:Genetic Variation; D005838:Genotype; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D015658:HIV Infections / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood / Q000302:isolation & purification; D019713:Receptors, CCR5 / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D000069585:Filgrastim