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Clinical Research and Public HealthIn-Press PreviewAIDS/HIVInflammation Open Access | 10.1172/JCI196869

Age modifies the association between sex and the plasma inflammatory proteome in treated HIV

Rebecca A. Abelman,1 Samuel R. Schnittman,2 Natalia Faraj Murad,1 Adam Olshen,1 Gabriele B. Beck-Engeser,1 Noah Aquino,1 Gabrielle C. Ambayec,1 Edward R. Cachay,3 Joseph J. Eron,4 Michael Saag,5 Robin M. Nance,6 Joseph A. Delaney,6 Stephanie A. Ruderman,6 Richard D. Moore,7 Kenneth H. Mayer,8 Jeffrey M. Jacobson,9 Heidi M. Crane,6 and Peter W. Hunt1

1UCSF, San Francisco, United States of America

2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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1UCSF, San Francisco, United States of America

2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

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8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

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9Case Western Reserve University, Cleveland, United States of America

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5University of Alabama at Birmingham, Birmingham, United States of America

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7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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2Amgen, Thousand Oaks, United States of America

3Mayo Clinic, Scottsdale, United States of America

4University of North Carolina, Chapel Hill, United States of America

5University of Alabama at Birmingham, Birmingham, United States of America

6University of Washington, Seattle, United States of America

7Johns Hopkins University School of Medicine, Baltimore, United States of America

8The Fenway Institute, Boston, United States of America

9Case Western Reserve University, Cleveland, United States of America

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Published December 9, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI196869.
Copyright © 2025, Abelman et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 9, 2025 - Version history
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Abstract

BACKGROUND. Among antiretroviral therapy (ART)-suppressed people with HIV (PWH), women have higher levels of some inflammatory markers than men, but the broader effect of sex on the inflammatory proteome, and whether these differences are modified by age, remains unclear.

METHODS. 363 plasma inflammatory protein levels (Olink Inflammation Explore) were assessed in ART-suppressed PWH sampled from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The relationship between sex and 363 plasma proteins – including 22 in the interferon-α response pathway – was assessed with linear regression models adjusting for confounders, assessing interactions by age.

FINDINGS. Of 922 participants, 162 (18%) were female. The median age was 47, above which the majority of women had undetectable plasma anti-Müllerian hormone levels, a biomarker of ovarian reserve. Age impacted the influence of sex on the inflammatory proteome. Older age (>47) was associated with greater increases among women than men in 194 proteins. Interferon-α response proteins were higher in men in those ≤ 47 (P = 0.024), but higher in women in those > 47 (P = 0.005, p-interaction < 0.001). Among the 131 proteins associated with mortality risk (q < 0.05), only 5 differed by sex among those ≤ 47, while 79 differed by sex in those > 47, with nearly all being higher in women . Women had decreased mortality than men ≤47 (P < 0.001) but had similar mortality > 47 (P = 0.84).

INTERPRETATION. The menopausal transition appears to have a dramatic effect on systemic Type I interferon responses and the broader inflammatory proteome in women with HIV. Among older PWH, women have greater inflammation than men, including the majority of proteins linked with mortality risk.

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  • Version 1 (December 9, 2025): In-Press Preview
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