Post-treatment control of HIV infection

Conway, Jessica M.; Perelson, Alan S.

doi:10.1073/pnas.1419162112

Post-treatment control of HIV infection

Journal Article · Mon Apr 13 00:00:00 UTC 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1419162112· OSTI ID:1233166

Conway, Jessica M. ^[1]; Perelson, Alan S. ^[2]

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)

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.

View Accepted Manuscript (DOE)

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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From Individual Health to Community Health: Towards Multiscale Modeling of Directly Transmitted Infectious Disease Systems Garira, Winston; Mafunda, Martin Canaan Journal of Biological Systems, Vol. 27, Issue 01 https://doi.org/10.1142/s0218339019500074	journal	March 2019
HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers Sharaf, Radwa; Lee, Guinevere Q.; Sun, Xiaoming Journal of Clinical Investigation, Vol. 128, Issue 9 https://doi.org/10.1172/jci120549	journal	August 2018
Dual targeting of the thioredoxin and glutathione systems in cancer and HIV Benhar, Moran; Shytaj, Iart Luca; Stamler, Jonathan S. Journal of Clinical Investigation, Vol. 126, Issue 5 https://doi.org/10.1172/jci85339	journal	May 2016
Life cycle synchronization is a viral drug resistance mechanism Neagu, Iulia A.; Olejarz, Jason; Freeman, Mark PLOS Computational Biology, Vol. 14, Issue 2 https://doi.org/10.1371/journal.pcbi.1005947	journal	February 2018
HIV control: Is getting there the same as staying there? Goulder, Philip; Deeks, Steven G. PLOS Pathogens, Vol. 14, Issue 11 https://doi.org/10.1371/journal.ppat.1007222	journal	November 2018
CD8+ lymphocyte control of SIV infection during antiretroviral therapy Cao, Youfang; Cartwright, Emily K.; Silvestri, Guido PLOS Pathogens, Vol. 14, Issue 10 https://doi.org/10.1371/journal.ppat.1007350	journal	October 2018
HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers R., Mitsuyasu,; M., Lichterfeld,; G. Q., Lee, American Society for Clinical Investigation https://doi.org/10.17615/z2cw-gb29	text	January 2018
Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure Clutton, Genevieve Tyndale; Jones, R. Brad Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.01452	journal	June 2018
Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV Hill, Alison L.; Rosenbloom, Daniel; Goldstein, Edward Columbia University https://doi.org/10.7916/d8m61k94	text	January 2016

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