CD133+ hematopoietic progenitor cells harbor HIV genomes in a subset of optimally treated people with long-term viral suppression

J Infect Dis. 2013 Jun 15;207(12):1807-16. doi: 10.1093/infdis/jit118. Epub 2013 Apr 3.

Abstract

Background: Hematopoietic progenitor cells (HPCs) in the bone marrow of human immunodeficiency virus (HIV)-infected individuals have been proposed as a persistent reservoir of virus. However, some studies have suggested that HIV genomes detected in HPCs arise from T-cell contamination.

Methods: CD133-sorted HPCs and CD133-depleted bone marrow cells were purified from bone marrow specimens obtained from 11 antiretroviral-treated donors in whom the HIV load had been <48 copies/mL for at least 6 months. CD133 and CD3 expression on the cells was assessed by flow cytometry. HIV DNA was quantified by real-time polymerase chain reaction analysis.

Results: HIV genomes were detected in CD133-sorted samples from 6 donors, including 2 in whom viral loads were undetectable for >8 years. CD3(+) T cells represented <1% of cells in all CD133-sorted samples. For 5 of 6 CD133-sorted samples with detectable HIV DNA, the HIV genomes could not be explained by contaminating CD3(+) T cells. Donors with detectable HIV DNA in HPCs received their diagnosis significantly more recently than the remaining donors but had had undetectable viral loads for similar periods.

Conclusions: HIV genomes can be detected in CD133-sorted cells from a subset of donors with long-term viral suppression and, in most cases, cannot be explained by contamination with CD3(+) T cells.

Keywords: HIV; hematopoietic progenitor cells; reservoirs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Anti-Retroviral Agents / therapeutic use*
  • Antigens, CD / metabolism*
  • Bone Marrow / virology
  • CD3 Complex / metabolism
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Genome, Viral / genetics*
  • Glycoproteins / metabolism*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / isolation & purification*
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / virology*
  • Humans
  • Peptides / metabolism*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Viral Load

Substances

  • AC133 Antigen
  • Anti-Retroviral Agents
  • Antigens, CD
  • CD3 Complex
  • DNA, Viral
  • Glycoproteins
  • PROM1 protein, human
  • Peptides