Anti-proliferative therapy for HIV cure: a compound interest approach

Abstract In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integra...

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Auteurs principaux: Daniel B. Reeves, Elizabeth R. Duke, Sean M. Hughes, Martin Prlic, Florian Hladik, Joshua T. Schiffer
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Langue:EN
Publié: Nature Portfolio 2017
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Accès en ligne:https://doaj.org/article/3bd56a0f58ac4f5799ab988ad7daaffa
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spelling oai:doaj.org-article:3bd56a0f58ac4f5799ab988ad7daaffa2021-12-02T15:05:07ZAnti-proliferative therapy for HIV cure: a compound interest approach10.1038/s41598-017-04160-32045-2322https://doaj.org/article/3bd56a0f58ac4f5799ab988ad7daaffa2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04160-3https://doaj.org/toc/2045-2322Abstract In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4+ T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2–10 years rather than several decades on ART alone.Daniel B. ReevesElizabeth R. DukeSean M. HughesMartin PrlicFlorian HladikJoshua T. SchifferNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Daniel B. Reeves
Elizabeth R. Duke
Sean M. Hughes
Martin Prlic
Florian Hladik
Joshua T. Schiffer
Anti-proliferative therapy for HIV cure: a compound interest approach
description Abstract In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4+ T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2–10 years rather than several decades on ART alone.
format article
author Daniel B. Reeves
Elizabeth R. Duke
Sean M. Hughes
Martin Prlic
Florian Hladik
Joshua T. Schiffer
author_facet Daniel B. Reeves
Elizabeth R. Duke
Sean M. Hughes
Martin Prlic
Florian Hladik
Joshua T. Schiffer
author_sort Daniel B. Reeves
title Anti-proliferative therapy for HIV cure: a compound interest approach
title_short Anti-proliferative therapy for HIV cure: a compound interest approach
title_full Anti-proliferative therapy for HIV cure: a compound interest approach
title_fullStr Anti-proliferative therapy for HIV cure: a compound interest approach
title_full_unstemmed Anti-proliferative therapy for HIV cure: a compound interest approach
title_sort anti-proliferative therapy for hiv cure: a compound interest approach
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/3bd56a0f58ac4f5799ab988ad7daaffa
work_keys_str_mv AT danielbreeves antiproliferativetherapyforhivcureacompoundinterestapproach
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AT seanmhughes antiproliferativetherapyforhivcureacompoundinterestapproach
AT martinprlic antiproliferativetherapyforhivcureacompoundinterestapproach
AT florianhladik antiproliferativetherapyforhivcureacompoundinterestapproach
AT joshuatschiffer antiproliferativetherapyforhivcureacompoundinterestapproach
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