Post-treatment control of HIV infection
Abstract
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.
- Authors:
-
- The Pennsylvania State Univ., University Park, PA (United States); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1233166
- Report Number(s):
- LA-UR-14-27986
Journal ID: ISSN 0027-8424
- Grant/Contract Number:
- R01-AI028433; UM1-AI100645; AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 112; Journal Issue: 17; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; HIV latency; post-treatment control; mathematical modeling; immune exhaustion
Citation Formats
Conway, Jessica M., and Perelson, Alan S. Post-treatment control of HIV infection. United States: N. p., 2015.
Web. doi:10.1073/pnas.1419162112.
Conway, Jessica M., & Perelson, Alan S. Post-treatment control of HIV infection. United States. https://doi.org/10.1073/pnas.1419162112
Conway, Jessica M., and Perelson, Alan S. Mon .
"Post-treatment control of HIV infection". United States. https://doi.org/10.1073/pnas.1419162112. https://www.osti.gov/servlets/purl/1233166.
@article{osti_1233166,
title = {Post-treatment control of HIV infection},
author = {Conway, Jessica M. and Perelson, Alan S.},
abstractNote = {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.},
doi = {10.1073/pnas.1419162112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 17,
volume = 112,
place = {United States},
year = {Mon Apr 13 00:00:00 EDT 2015},
month = {Mon Apr 13 00:00:00 EDT 2015}
}
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