IL-10 and Coordinated Cytokine Responses Predict Rapid HIV Reservoir Decay in Acute Treated HIV Infection
Abstract
BackgroundThe HIV reservoir is established within days of infection and persists despite antiretroviral therapy (ART). Host immune responses associated with early reservoir decay remain poorly defined.
MethodsWe analyzed > 500 longitudinal blood samples from 67 individuals treated during acute HIV infection. Plasma cytokines and HIV reservoir size (intact and defective DNA) were quantified longitudinally. Cytokine-reservoir relationships were assessed using unsupervised clustering and complementary mixed-effects nonlinear and linear spline models; counterfactual modeling examined how cytokine concentrations at defined timepoints related to subsequent reservoir trajectories.
ResultsTNF-, IL-17A, and IL-10 were significantly associated with intact HIV DNA during the first 24 weeks of ART after false-discovery-rate correction. TNF- showed one of the strongest associations with intact reservoir decay, whereas IL-10 showed the most consistent association across intact and defective HIV DNA. A coordinated cytokine cluster comprising IFN-{gamma}, IL-10, IL-18, and TNF- was associated with both reservoir measures. Phase-specific and counterfactual analyses further suggested that associations between several cytokines and reservoir dynamics varied with timing during early ART. These relationships persisted after adjustment for ART initiation timing, baseline viremia, initial CD4+ T-cell count, and longitudinal CD4:CD8 ratio.
DiscussionCoordinated inflammatory, antiviral, and immunoregulatory cytokine responses are associated with HIV reservoir decay following ART initiation during acute infection, with some relationships varying over time. These findings may inform future stage-specific HIV cure strategies that leverage the timing and balance of antiviral, inflammatory, and immunoregulatory pathways to limit reservoir persistence.
Main SummaryIn people initiating ART during acute HIV infection, coordinated inflammatory, antiviral, and immunoregulatory cytokine responses were associated with faster HIV reservoir decay, with TNF- and IL-10 showing particularly strong and consistent associations.
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BibTeX
@misc{barbehenn2026il10,
title = {{IL-10 and Coordinated Cytokine Responses Predict Rapid HIV Reservoir Decay in Acute Treated HIV Infection}},
author = {Alton Barbehenn and Erik Lundgren and Sonia Savur and Lei Shi and Junzhe Shao and Rebecca Hoh and Heather M. Hartig and Vivian Pae and Sannidhi Sarvadhavabhatla and Sophia Donaire and Caroline H. Sheikhzadeh and Jeffrey Milush and Gregory M. Laird and Mignot Mathias and Kristen Ritter and Jeffrey Martin and Frederick Hecht and Christopher Pilcher and Stephanie E. Cohen and Susan Buchbinder and Diane Havlir and Monica Gandhi and Timothy J. Henrich and Hiroyu Hatano and Susan P. Ribeiro and Jeffrey A. Tomalka and Steven G. Deeks and Rafick P. Sekaly and Jingshen Wang and Aaron Hudson and Sulggi A. Lee},
howpublished = {medRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.18.26360728},
url = {https://www.medrxiv.org/content/10.64898/2026.08.18.26360728v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - IL-10 and Coordinated Cytokine Responses Predict Rapid HIV Reservoir Decay in Acute Treated HIV Infection
AU - Alton Barbehenn
AU - Erik Lundgren
AU - Sonia Savur
AU - Lei Shi
AU - Junzhe Shao
AU - Rebecca Hoh
AU - Heather M. Hartig
AU - Vivian Pae
AU - Sannidhi Sarvadhavabhatla
AU - Sophia Donaire
AU - Caroline H. Sheikhzadeh
AU - Jeffrey Milush
AU - Gregory M. Laird
AU - Mignot Mathias
AU - Kristen Ritter
AU - Jeffrey Martin
AU - Frederick Hecht
AU - Christopher Pilcher
AU - Stephanie E. Cohen
AU - Susan Buchbinder
AU - Diane Havlir
AU - Monica Gandhi
AU - Timothy J. Henrich
AU - Hiroyu Hatano
AU - Susan P. Ribeiro
AU - Jeffrey A. Tomalka
AU - Steven G. Deeks
AU - Rafick P. Sekaly
AU - Jingshen Wang
AU - Aaron Hudson
AU - Sulggi A. Lee
PY - 2026
DA - 2026/08/18
PB - medRxiv
DO - 10.64898/2026.08.18.26360728
UR - https://www.medrxiv.org/content/10.64898/2026.08.18.26360728v1
AB - BackgroundThe HIV reservoir is established within days of infection and persists despite antiretroviral therapy (ART). Host immune responses associated with early reservoir decay remain poorly defined. MethodsWe analyzed > 500 longitudinal blood samples from 67 individuals treated during acute HIV infection. Plasma cytokines and HIV reservoir size (intact and defective DNA) were quantified longitudinally. Cytokine-reservoir relationships were assessed using unsupervised clustering and complementary mixed-effects nonlinear and linear spline models; counterfactual modeling examined how cytokine concentrations at defined timepoints related to subsequent reservoir trajectories. ResultsTNF-, IL-17A, and IL-10 were significantly associated with intact HIV DNA during the first 24 weeks of ART after false-discovery-rate correction. TNF- showed one of the strongest associations with intact reservoir decay, whereas IL-10 showed the most consistent association across intact and defective HIV DNA. A coordinated cytokine cluster comprising IFN-{gamma}, IL-10, IL-18, and TNF- was associated with both reservoir measures. Phase-specific and counterfactual analyses further suggested that associations between several cytokines and reservoir dynamics varied with timing during early ART. These relationships persisted after adjustment for ART initiation timing, baseline viremia, initial CD4+ T-cell count, and longitudinal CD4:CD8 ratio. DiscussionCoordinated inflammatory, antiviral, and immunoregulatory cytokine responses are associated with HIV reservoir decay following ART initiation during acute infection, with some relationships varying over time. These findings may inform future stage-specific HIV cure strategies that leverage the timing and balance of antiviral, inflammatory, and immunoregulatory pathways to limit reservoir persistence. Main SummaryIn people initiating ART during acute HIV infection, coordinated inflammatory, antiviral, and immunoregulatory cytokine responses were associated with faster HIV reservoir decay, with TNF- and IL-10 showing particularly strong and consistent associations.
ER -