Residual cell-associated unspliced HIV-1 RNA in peripheral blood of patients on potent antiretroviral therapy represents intracellular transcripts

Antivir Ther. 2002 Jun;7(2):91-103.


Unspliced HIV-RNA (HIV-UsRNA) associated with peripheral blood mononuclear cells (PBMCs) persists in patients on potent antiretroviral therapy even in the absence of detectable plasma HIV-RNA. To further characterize such residual HIV-RNA, cell-associated virion-encapsidated HIV and intracellular unspliced HIV-RNA were differentiated and monitored using a novel highly sensitive method. In addition, expression of HIV-mRNA encoding tat and rev was assessed. PBMCs of patients with unsuppressed plasma viraemia harboured an extracellular fraction of HIV-UsRNA, which correlated highly with intracellular HIV-RNA levels. Thus, extracellular PBMC-associated HIV-RNA may, to a significant extent, reflect nascent virions attached to productively infected cells. Upon treatment with potent antiretroviral therapy resulting in plasma viraemia <50 copies/ml, expression of cell-associated viral particles was hardly discernible in PBMCs but transcription of unspliced HIV-RNA persisted. Given the virtual absence of rev-mRNA, translation of residual HIV-UsRNA was probably precluded by retention of these transcripts in the nucleus. As shown by limiting dilution analysis, HIV-1 infected cells with such a repressed viral transcription pattern were observed at high frequencies in PBMC from untreated patients.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / therapeutic use*
  • Cell Line
  • Cohort Studies
  • Genes, rev
  • Genes, tat
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • Humans
  • Leukocytes, Mononuclear / virology*
  • RNA, Messenger / analysis
  • RNA, Viral / blood*


  • Anti-HIV Agents
  • RNA, Messenger
  • RNA, Viral