Post-treatment control of HIV infection

Jessica Maral Conway, Alan S. Perelson

Research output: Contribution to journalArticle

65 Citations (Scopus)

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. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.

Original languageEnglish (US)
Pages (from-to)5467-5472
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number17
DOIs
StatePublished - Apr 28 2015

Fingerprint

HIV Infections
HIV
Cytotoxic T-Lymphocytes
Therapeutics
Infection
Adaptive Immunity
Virus Diseases
Theoretical Models
RNA
Viruses
Population

All Science Journal Classification (ASJC) codes

  • General

Cite this

@article{16f87aab843d421e8abdae20d7bfed7e,
title = "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. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.",
author = "Conway, {Jessica Maral} and Perelson, {Alan S.}",
year = "2015",
month = "4",
day = "28",
doi = "10.1073/pnas.1419162112",
language = "English (US)",
volume = "112",
pages = "5467--5472",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "17",

}

Post-treatment control of HIV infection. / Conway, Jessica Maral; Perelson, Alan S.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 17, 28.04.2015, p. 5467-5472.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Post-treatment control of HIV infection

AU - Conway, Jessica Maral

AU - Perelson, Alan S.

PY - 2015/4/28

Y1 - 2015/4/28

N2 - 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. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.

AB - 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. Using data on latent reservoir sizes in patients treated during primary infection, we also predict population-level VR times for noncontrollers consistent with observations.

UR - http://www.scopus.com/inward/record.url?scp=84928718905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928718905&partnerID=8YFLogxK

U2 - 10.1073/pnas.1419162112

DO - 10.1073/pnas.1419162112

M3 - Article

C2 - 25870266

AN - SCOPUS:84928718905

VL - 112

SP - 5467

EP - 5472

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 17

ER -