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Impact of fluctuation in frequency of human immunodeficiency virus/simian immunodeficiency virus reactivation during antiretroviral therapy interruption

  1. Author:
    Wu, Yuhuang
    Pinkevych, Mykola
    Xu, Zhuang
    Keele,Brandon
    Davenport, Miles P
    Cromer, Deborah

  2. Author Address

    Infection Analytics Program, Kirby Institute for Infection and Immunity, University of New South Wales, Sydney, NSW, Australia., School of Physics, University of New South Wales, Sydney, NSW, Australia., AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., School of Mathematics and Statistics, University of New South Wales, Sydney, NSW, Australia.,
    1. Year: 2020
    2. Date: Aug 26
    3. Epub Date: 2020 08 19
  2. Journal: Proceedings. Biological sciences
    1. 287
    2. 1933
    3. Pages: 20200354
  4. Type of Article: Article
  5. Article Number: 20200354
  6. ISSN: 0962-8452
  1. Abstract:

    Antiretroviral therapy (ART) provides effective control of human immunodeficiency virus (HIV) replication and maintains viral loads of HIV at undetectable levels. Interruption of ART causes rapid recrudescence of HIV plasma viremia due to reactivation of latently HIV-infected cells. Here, we characterize the timing of both the initial and subsequent successful viral reactivations following ART interruption in macaques infected with simian immunodeficiency virus (SIV). We compare these to previous results from HIV-infected patients. We find that on average the time until the first successful viral reactivation event is longer than the time between subsequent reactivations. Based on this result, we hypothesize that the reactivation frequency of both HIV and SIV may fluctuate over time, and that this may impact the treatment of HIV. We develop a stochastic model incorporating fluctuations in the frequency of viral reactivation following ART interruption that shows behaviours consistent with the observed data. Furthermore, we show that one of the impacts of a fluctuating reactivation frequency would be to significantly reduce the efficacy of 39;anti-latency 39; interventions for HIV that aim to reduce the frequency of reactivation. It is therefore essential to consider the possibility of a fluctuating reactivation frequency when assessing the impact of such intervention strategies.

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External Sources

  1. View Full Text
  2. DOI: 10.1098/rspb.2020.0354
  3. PMID: 32811309
  4. View record in Web of Science®
  5. WOS: 000563925900007

Library Notes

  1. Fiscal Year: FY2019-2020
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