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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Autores principales:	Daniel B. Reeves, Elizabeth R. Duke, Sean M. Hughes, Martin Prlic, Florian Hladik, Joshua T. Schiffer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	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 AT elizabethrduke antiproliferativetherapyforhivcureacompoundinterestapproach AT seanmhughes antiproliferativetherapyforhivcureacompoundinterestapproach AT martinprlic antiproliferativetherapyforhivcureacompoundinterestapproach AT florianhladik antiproliferativetherapyforhivcureacompoundinterestapproach AT joshuatschiffer antiproliferativetherapyforhivcureacompoundinterestapproach
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Anti-proliferative therapy for HIV cure: a compound interest approach

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