Shifts in cell-associated HIV-1 RNA but not in episomal HIV-1 DNA correlate with new cycles of HIV-1 infection in vivo.
The significance of distinct classes of HIV-1 nucleic acids as correlates of recent HIV-1 replication was assessed in peripheral blood mononuclear cells (PBMC) obtained from 14 patients during 2 weeks of structured interruption of antiretroviral therapy (STI) and 2 weeks of resuming therapy. Levels of HIV RNA in plasma (HIV-RNAplasma) and of unspliced cell-associated HIV-1 RNA (HIV-UsRNAPBMC) were significantly increased as a result of STI, whereas no significant shifts in the levels of 2-LTR episomal HIV-1 DNA (2-LTR circles) and total late HIV-1 reverse transcripts (late-DNA) were observed. Thus, limited viral replication had occurred, which had no effect on the pool size of infected cells in the periphery. Levels of 2-LTR circles did not reflect rapid changes in HIV-1 replication. In contrast, expression of HIV-UsRNAPBMC increased during STI and consequently provides a more sensitive, albeit not absolute cellular marker of ongoing HIV-1 replication.
Division of Infectious Diseases and Hospital Epidemiology, Department of Medicine, University Hospital Zürich, 8091 Zürich, Switzerland. marek.fischer@usz.ch
Marek
M
Fischer
Alexandra
A
Trkola
Beda
B
Joos
Roland
R
Hafner
Helen
H
Joller
Mark A
MA
Muesing
David R
DR
Kaufman
Esther
E
Berli
Bernard
B
Hirschel
Rainer
R
Weber
Huldrych F
HF
Günthard
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D002457:Cell Extracts / Q000235:genetics; D002478:Cells, Cultured; D004279:DNA, Viral / Q000097:blood*; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008137:Longitudinal Studies; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D014779:Virus Replication
D019380:Anti-HIV Agents; D015415:Biomarkers; D002457:Cell Extracts; D004279:DNA, Viral; D012367:RNA, Viral