HIV-1 viruses detected during episodic blips following interleukin-7 administration are similar to the viruses present before and after interleukin-7 therapy.
BACKGROUND
administration of recombinant human interleukin (IL)-7 leads to CD4 and CD8 T-cell expansions in HIV-infected individuals, demonstrating promising capacity for immune reconstitution. However, a proportion of patients treated with recombinant human IL-7 experience transient increases in plasma HIV-RNA ('blips'), possibly reflecting 'purging' of a quiescent reservoir that provides a barrier to viral eradication.


OBJECTIVE
to identify the sources of HIV detected during transient viremic episodes following IL-7 administration, viral quasispecies were analyzed in a total of 281 primary sequences derived from seven patients who experienced the episodic blips following IL-7 therapy.


METHODS
the C2-V3 regions of the HIV-1 env gene were sequenced from HIV-1 RNA in plasma and HIV DNA from peripheral blood mononuclear cells (PBMCs) obtained at baseline (day 0 of recombinant human IL-7 therapy), during the episode of viral blips (day 4), and at a time when levels of plasma HIV-RNA had returned to less than 50 copies/ml (day 28).


RESULTS
the HIV sequences detected during transient viremia following IL-7 administration were closely related to those of the plasma viruses present before and after cytokine administration. All virus quasispecies detected during blips were also present in proviral sequences in PBMCs.


CONCLUSIONS
the low level viremia induced by IL-7 likely reflects predominantly transient induction or release of virus from a preexisting pool rather than activation of silent quasispecies.
Clinical and Molecular Retrovirology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA. himamichi@nih.gov
Hiromi
H
Imamichi
Gerald
G
Degray
David M
DM
Asmuth
Margaret A
MA
Fischl
Alan L
AL
Landay
Michael M
MM
Lederman
Irini
I
Sereti
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015752:Genes, env / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral; D019562:Viral Load; D014766:Viremia; D017735:Virus Latency / Q000235:genetics
C508605:IL7 protein, human; D015851:Interleukin-7; D012367:RNA, Viral