Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy

J Virol. 2002 Jan;76(2):707-16. doi: 10.1128/jvi.76.2.707-716.2002.


In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14(+) monocytes and resting and activated CD4(+) T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14(+) monocytes as well as in activated and resting CD4(+) T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14(+) monocytes was on average slower than that in activated and resting CD4(+) T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14(+) monocytes than in resting CD4(+) T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14(+) monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14(+) monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Division
  • Evolution, Molecular
  • Gene Expression Regulation, Viral
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Half-Life
  • Humans
  • Lipopolysaccharide Receptors / metabolism*
  • Lymphocyte Activation
  • Male
  • Molecular Sequence Data
  • Monocytes / metabolism
  • Monocytes / virology*
  • Organ Specificity
  • Phylogeny
  • Proviruses / genetics
  • Proviruses / isolation & purification
  • Proviruses / physiology
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Transcription, Genetic
  • Virion / chemistry
  • Virion / genetics
  • Virion / isolation & purification
  • Virion / physiology
  • Virus Replication*


  • Anti-HIV Agents
  • HIV Envelope Protein gp120
  • Lipopolysaccharide Receptors
  • RNA, Viral