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Assays to Measure Latency, Reservoirs, and Reactivation

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HIV-1 Latency

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 417))

Abstract

HIV-1 persists even in patients who are successfully treated with combination antiretroviral therapy. The major barrier to cure is a small pool of latently infected resting CD4+ T cells carrying an integrated copy of the viral genome that is not expressed while the cells remain in a resting state. Targeting this latent reservoir is a major focus of HIV-1 cure research, and the development of a rapid and scalable assay for the reservoir is a rate-limiting step in the search for a cure. The most commonly used assays are standard PCR assays targeting conserved regions of the HIV-1 genome. However, because the vast majority of HIV-1 proviruses are defective, such assays may not accurately capture changes in the minor subset of proviruses that are replication-competent and that pose a barrier to cure. On the other hand, the viral outgrowth assay that was used to initially define the latent reservoir may underestimate reservoir size because not all replication-competent proviruses are induced by a single round of T cell activation in this assay. Therefore, this assay is best regarded as a definitive minimal estimate of reservoir size. The best approach may be to measure all of the proviruses with the potential to cause viral rebound. A variety of novel assays have recently been described. Ultimately, the assay that best predicts time to viral rebound will be the most useful to the cure effort.

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Acknowledgements

This work was supported by the NIH Martin Delaney I4C, Beat-HIV and DARE Collaboratories, by the Johns Hopkins Center for AIDS Research (P30AI094189), by NIH grant 43222, and by the Howard Hughes Medical Institute and the Bill and Melinda Gates Foundation.

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Authors and Affiliations

  1. Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Janet D. Siliciano

  2. Johns Hopkins University School of Medicine, Howard Hughes Medical Institute, Baltimore, MD, 21205, USA

    Robert F. Siliciano

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  1. Janet D. Siliciano
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  2. Robert F. Siliciano
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Correspondence to Robert F. Siliciano .

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Editors and Affiliations

  1. School of Medicine, Emory University, Atlanta, GA, USA

    Guido Silvestri

  2. The Brigham and Women’s Hospital and the Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA

    Mathias Lichterfeld

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Siliciano, J.D., Siliciano, R.F. (2017). Assays to Measure Latency, Reservoirs, and Reactivation. In: Silvestri, G., Lichterfeld, M. (eds) HIV-1 Latency. Current Topics in Microbiology and Immunology, vol 417. Springer, Cham. https://doi.org/10.1007/82_2017_75

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