Longitudinal Genetic Characterization Reveals That Cell Proliferation Maintains a Persistent HIV Type 1 DNA Pool During Effective HIV Therapy

J Infect Dis. 2015 Aug 15;212(4):596-607. doi: 10.1093/infdis/jiv092. Epub 2015 Feb 23.


Background: The stability of the human immunodeficiency virus type 1 (HIV-1) reservoir and the contribution of cellular proliferation to the maintenance of the reservoir during treatment are uncertain. Therefore, we conducted a longitudinal analysis of HIV-1 in T-cell subsets in different tissue compartments from subjects receiving effective antiretroviral therapy (ART).

Methods: Using single-proviral sequencing, we isolated intracellular HIV-1 genomes derived from defined subsets of CD4(+) T cells from peripheral blood, gut-associated lymphoid tissue and lymph node tissue specimens from 8 subjects with virologic suppression during long-term ART at 2 time points (time points 1 and 2) separated by 7-9 months.

Results: DNA integrant frequencies were stable over time (<4-fold difference) and highest in memory T cells. Phylogenetic analyses showed that subjects treated during chronic infection contained viral populations with up to 73% identical sequence expansions, only 3 of which were observed in specimens obtained before therapy. At time points 1 and 2, such clonally expanded populations were found predominantly in effector memory T cells from peripheral blood and lymph node tissue specimens.

Conclusions: Memory T cells maintained a relatively constant HIV-1 DNA integrant pool that was genetically stable during long-term effective ART. These integrants appear to be maintained by cellular proliferation and longevity of infected cells, rather than by ongoing viral replication.

Keywords: HIV-1 persistence; HIV-1 reservoir; memory T cells.

Publication types

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

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Cell Proliferation
  • DNA, Viral / genetics*
  • DNA, Viral / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • Humans
  • Longitudinal Studies
  • Lymph Nodes / virology
  • Phylogeny
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocyte Subsets / virology*


  • Anti-HIV Agents
  • DNA, Viral