Transient increases in inflammatory cytokines and chemokines are predictive of subsequent HIV-1 infection
Abstract
BackgroundCurrent HIV prevention strategies focus on targeting ‘at-risk’ individuals with sexual health education and HIV prevention medications such as PrEP. Despite these efforts, ~1.3 million new infections occur globally each year. We therefore asked whether it is possible to further stratify ‘at-risk’ individuals into high- and low-risk categories, enabling more targeted intervention toward those most vulnerable.MethodsTo explore this, we screened plasma samples from HIV-negative partners in serodiscordant couples in Zambia and Rwanda for hallmark inflammatory cytokines. We compared cytokine levels between individuals who remained uninfected and those who later seroconverted (pre-infected).ResultsAnalysis of plasma from 501 uninfected individuals and 91 pre-infected individuals identified several significantly elevated cytokines in pre-infected individuals with IL-7, ITAC, and IL-8 being the most significantTo assess whether these elevations were transient or chronic, we analyzed earlier pre-infection samples collected up to 18 months before estimated date of infection (EDI) in Zambia and up to 7 months pre-EDI in Rwanda. In Zambia, IL-7, ITAC, and IL-8 were significantly lower at the earlier time point, suggesting a transient increase prior to infection. No difference was observed in Rwanda, likely due to the shorter sampling interval, supporting the idea that these elevations occur within a limited window of time.To determine whether these diagnostic cytokines were elevated following infection, we analyzed longitudinal samples from pre-infection, early acute post-infection (0–3 months), and early-chronic post-infection (6–9 months). Identified biomarkers IL-7, IL-8 and ITAC showed a consistent decline following infection, with the most pronounced drop immediately following infection. Mixed-effects modelling quantified cytokine-specific longitudinal changes across pre-early and early-late post-infection intervals, confirming the univariable analyses.DiscussionOverall, we identified key plasma biomarkers that may help distinguish individuals at elevated risk of HIV acquisition which could inform more targeted prevention strategies.
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BibTeX
@article{rhodes2026transient,
title = {{Transient increases in inflammatory cytokines and chemokines are predictive of subsequent HIV-1 infection}},
author = {Jake William Rhodes and Shabir Lakhi and Etienne Karita and William Kilembe and Mubiana Inambao and Julien Nyombayire and Jill Gilmour and Susan A. Allen and Eric Hunter},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1958647},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958647},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transient increases in inflammatory cytokines and chemokines are predictive of subsequent HIV-1 infection
AU - Jake William Rhodes
AU - Shabir Lakhi
AU - Etienne Karita
AU - William Kilembe
AU - Mubiana Inambao
AU - Julien Nyombayire
AU - Jill Gilmour
AU - Susan A. Allen
AU - Eric Hunter
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1958647
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1958647
AB - BackgroundCurrent HIV prevention strategies focus on targeting ‘at-risk’ individuals with sexual health education and HIV prevention medications such as PrEP. Despite these efforts, ~1.3 million new infections occur globally each year. We therefore asked whether it is possible to further stratify ‘at-risk’ individuals into high- and low-risk categories, enabling more targeted intervention toward those most vulnerable.MethodsTo explore this, we screened plasma samples from HIV-negative partners in serodiscordant couples in Zambia and Rwanda for hallmark inflammatory cytokines. We compared cytokine levels between individuals who remained uninfected and those who later seroconverted (pre-infected).ResultsAnalysis of plasma from 501 uninfected individuals and 91 pre-infected individuals identified several significantly elevated cytokines in pre-infected individuals with IL-7, ITAC, and IL-8 being the most significantTo assess whether these elevations were transient or chronic, we analyzed earlier pre-infection samples collected up to 18 months before estimated date of infection (EDI) in Zambia and up to 7 months pre-EDI in Rwanda. In Zambia, IL-7, ITAC, and IL-8 were significantly lower at the earlier time point, suggesting a transient increase prior to infection. No difference was observed in Rwanda, likely due to the shorter sampling interval, supporting the idea that these elevations occur within a limited window of time.To determine whether these diagnostic cytokines were elevated following infection, we analyzed longitudinal samples from pre-infection, early acute post-infection (0–3 months), and early-chronic post-infection (6–9 months). Identified biomarkers IL-7, IL-8 and ITAC showed a consistent decline following infection, with the most pronounced drop immediately following infection. Mixed-effects modelling quantified cytokine-specific longitudinal changes across pre-early and early-late post-infection intervals, confirming the univariable analyses.DiscussionOverall, we identified key plasma biomarkers that may help distinguish individuals at elevated risk of HIV acquisition which could inform more targeted prevention strategies.
SN - 1664-3224
ER -