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Post-treatment control of HIV infection

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2]
  1. The Pennsylvania State Univ., University Park, PA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
+ Show Author Affiliations
Antiretroviral therapy (ART) for HIV is not a cure. However, recent studies suggest that ART, initiated early during primary infection, may induce post-treatment control (PTC) of HIV infection with HIV RNA maintained at <50 copies per mL. We investigate the hypothesis that ART initiated early during primary infection permits PTC by limiting the size of the latent reservoir, which, if small enough at treatment termination, may allow the adaptive immune response to prevent viral rebound (VR) and control infection. We use a mathematical model of within host HIV dynamics to capture interactions among target cells, productively infected cells, latently infected cells, virus, and cytotoxic T lymphocytes (CTLs). Analysis of our model reveals a range in CTL response strengths where a patient may show either VR or PTC, depending on the size of the latent reservoir at treatment termination. Below this range, patients will always rebound, whereas above this range, patients are predicted to behave like elite controllers. As a result, using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for non-controllers consistent with observations.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1233166
Report Number(s):
LA--UR-14-27986
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 17 Vol. 112; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English

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Thresholds and bistability in HIV infection models with oxidative stress preprint January 2018
Life cycle synchronization is a viral drug resistance mechanism text January 2018
Within-host and synaptic transmissions: contributions to the spread of HIV infection: A. R. M. CARVALHO AND C. M. A. PINTO journal June 2016
Stochastic Dynamics of the Latently Infected Cell Reservoir During HIV Infection journal October 2018
Modeling HIV Dynamics Under Combination Therapy with Inducers and Antibodies journal June 2019
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Why and where an HIV cure is needed and how it might be achieved journal December 2019
Probabilistic control of HIV latency and transactivation by the Tat gene circuit journal November 2018
A dynamical motif comprising the interactions between antigens and CD8 T cells may underlie the outcomes of viral infections journal August 2019
Herpes simplex virus-2 dynamics as a probe to measure the extremely rapid and spatially localized tissue-resident T-cell response journal August 2018
Mathematical modeling of within-host Zika virus dynamics journal August 2018
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Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV text January 2016

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV latency
immune exhaustion
mathematical modeling
post-treatment control