Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.

Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the...

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Main Authors: Tin Phan, Jessica M Conway, Nicole Pagane, Jasmine Kreig, Narmada Sambaturu, Sarafa Iyaniwura, Jonathan Z Li, Ruy M Ribeiro, Ruian Ke, Alan S Perelson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2024-07-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012236
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author Tin Phan
Jessica M Conway
Nicole Pagane
Jasmine Kreig
Narmada Sambaturu
Sarafa Iyaniwura
Jonathan Z Li
Ruy M Ribeiro
Ruian Ke
Alan S Perelson
author_facet Tin Phan
Jessica M Conway
Nicole Pagane
Jasmine Kreig
Narmada Sambaturu
Sarafa Iyaniwura
Jonathan Z Li
Ruy M Ribeiro
Ruian Ke
Alan S Perelson
author_sort Tin Phan
collection DOAJ
description Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.
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issn 1553-7366
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language English
publishDate 2024-07-01
publisher Public Library of Science (PLoS)
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series PLoS Pathogens
spelling doaj-art-ee7540f80b7145a281330191c24f05322025-08-20T02:36:58ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-07-01207e101223610.1371/journal.ppat.1012236Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.Tin PhanJessica M ConwayNicole PaganeJasmine KreigNarmada SambaturuSarafa IyaniwuraJonathan Z LiRuy M RibeiroRuian KeAlan S PerelsonMost people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.https://doi.org/10.1371/journal.ppat.1012236
spellingShingle Tin Phan
Jessica M Conway
Nicole Pagane
Jasmine Kreig
Narmada Sambaturu
Sarafa Iyaniwura
Jonathan Z Li
Ruy M Ribeiro
Ruian Ke
Alan S Perelson
Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
PLoS Pathogens
title Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
title_full Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
title_fullStr Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
title_full_unstemmed Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
title_short Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion.
title_sort understanding early hiv 1 rebound dynamics following antiretroviral therapy interruption the importance of effector cell expansion
url https://doi.org/10.1371/journal.ppat.1012236
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