Abstract
We examined the pathogenic significance of the latent viral reservoir in the resting CD4+ T cell compartment of HIV-1-infected individuals as well as its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and the replication-competent virus within the detectable pool of latently infected, resting CD4+ T cells. These results indicate the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.
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Acknowledgements
The authors thank C. Yoder and J. Metcalf for scheduling patient visits and for providing patient laboratory data. They also thank S. Moir for helpful discussions and review of the manuscript and the National Institute of Allergy and Infectious Disease Study Coordinators and Case Managers as well as their patients for their willingness to participate in these studies.
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Chun, TW., Davey, R., Ostrowski, M. et al. Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy . Nat Med 6, 757–761 (2000). https://doi.org/10.1038/77481
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DOI: https://doi.org/10.1038/77481
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