Cellular viral rebound after cessation of potent antiretroviral therapy predicted by levels of multiply spliced HIV-1 RNA encoding nef.
To characterize newly arising replication of human immunodeficiency virus (HIV) type 1 in vivo at the cellular level, distinct viral RNA species in peripheral blood mononuclear cells (PBMCs) from HIV-1-infected patients were monitored during 2 weeks of structured treatment interruption (STI). HIV-1 RNA encoding tat/rev and PBMC-associated virions were almost completely depleted during antiretroviral therapy and emerged simultaneously after 2 weeks of STI, thus specifically reflecting productive viral infection at the cellular level. The magnitude of these correlates of reappearing cellular viral replication was predicted by during-therapy levels of nef transcripts in PBMCs. Significant rebound of plasma viremia, representing the progeny of a broader range of anatomical compartments, preceded and predicted productive infection in PBMCs. Thus, cellular viral rebound in PBMCs likely was primed before STI by the expression of nef in HIV-1-infected PBMCs that lacked virion production and was subsequently triggered by the plasma viremia that preceded the recurrence of productively infected PBMCs.
Fischer
Marek
M
Division of Infectious Diseases and Hospital Epidemiology, Department of Medicine, University Hospital Zurich, CH-8091 Zurich, Switzerland. marek.fischer@usz.ch
Joos
Beda
B
Hirschel
Bernard
B
Bleiber
Gabriela
G
Weber
Rainer
R
Günthard
Huldrych F
HF
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D015693:Gene Products, nef / Q000032:analysis / Q000096:biosynthesis*; D015694:Gene Products, rev / Q000378:metabolism; D015696:Gene Products, tat / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D009504:Neutrophils / Q000821:virology; D012326:RNA Splicing; D012367:RNA, Viral / Q000032:analysis / Q000096:biosynthesis*; D012008:Recurrence; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015693:Gene Products, nef; D015694:Gene Products, rev; D015696:Gene Products, tat; D012367:RNA, Viral; D054311:nef Gene Products, Human Immunodeficiency Virus; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus