TY - JOUR
T1 - Biomarkers of microbial translocation and generalized inflammation are associated with frailty among people with HIV
AU - Ruderman, Stephanie A.
AU - Hunt, Peter W.
AU - Beck-Engeser, Gabriele
AU - Ambayec, Gabrielle
AU - Willig, Amanda L.
AU - Saag, Michael S.
AU - Napravnik, Sonia
AU - Cachay, Edward
AU - Bamford, Laura
AU - Landay, Alan
AU - Drumright, Lydia N.
AU - Mixson, L. Sarah
AU - Whitney, Bridget M.
AU - Nance, Robin M.
AU - Kitahata, Mari M.
AU - Crane, Heidi M.
AU - Delaney, Joseph A.C.
AU - Hahn, Andrew W.
N1 - Publisher Copyright:
© 2024 Wolters Kluwer Health, Inc.
PY - 2024
Y1 - 2024
N2 - Background: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH. Methods: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score. Results: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up. Conclusions: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.
AB - Background: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH. Methods: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score. Results: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up. Conclusions: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.
KW - biomarkers
KW - frailty
KW - inflammaging
KW - microbial translocation
KW - people with HIV
UR - http://www.scopus.com/inward/record.url?scp=85208684779&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85208684779&partnerID=8YFLogxK
U2 - 10.1097/QAD.0000000000004047
DO - 10.1097/QAD.0000000000004047
M3 - Article
C2 - 39453872
AN - SCOPUS:85208684779
SN - 0269-9370
JO - AIDS
JF - AIDS
M1 - 10.1097/QAD.0000000000004047
ER -