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Cellular viral rebound after cessation of potent antiretroviral therapy predicted by levels of multiply spliced HIV-1 RNA encoding nef

Fischer, Marek
Joos, Beda
Bleiber, Gabriela
Weber, Rainer
Gunthard, Huldrych
Published in The Journal of Infectious Diseases. 2004, vol. 190, no. 11, p. 1979-1988
Abstract 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.
Keywords Anti-HIV Agents/ therapeutic useCells, CulturedDrug Therapy, CombinationGene Products, nef/analysis/ biosynthesisGene Products, rev/metabolismGene Products, tat/metabolismHIV Infections/blood/ drug therapy/virologyHIV-1/genetics/ isolation & purificationHumansLeukocytes, Mononuclear/ virologyNeutrophils/virologyRNA SplicingRNA, Viral/analysis/ biosynthesisRecurrenceVirus ReplicationNef Gene Products, Human Immunodeficiency VirusRev Gene Products, Human Immunodeficiency VirusTat Gene Products, Human Immunodeficiency Virus
PMID: 15529263
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Other version: http://www.journals.uchicago.edu/doi/full/10.1086/425983
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FISCHER, Marek et al. Cellular viral rebound after cessation of potent antiretroviral therapy predicted by levels of multiply spliced HIV-1 RNA encoding nef. In: The Journal of Infectious Diseases, 2004, vol. 190, n° 11, p. 1979-1988. https://archive-ouverte.unige.ch/unige:7213

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Deposited on : 2010-06-21

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