A Biomarker Profile Reflective of Preserved Thymic Function Is Associated With Reduced Comorbidities in Aging People With HIV: An AGEhIV Cohort Analysis
Authors: Vanbellinghen Manon C , Boyd Anders , Kootstra Neeltje A , Schim van der Loeff Maarten F , van der Valk Marc , Reiss Peter ,   AGEhIV Cohort study group, Reiss P , Wit F W N M , van der Valk M , Boyd A , van der Wulp I A J , Vanbellinghen M C , van Eeden C J , van der Loeff M F Schim , del Grande L , Agard I , Zaheri S , Hillebregt M M J , Ruijs Y M C , Benschop D P , el Berkaoui A , Boyd A , Wit F W N M , Kootstra N A , Harskamp-Holwerda A M , Maurer I , Mangas Ruiz M M , Boeser-Nunnink B D N , Starozhitskaya O S , van der Hoek L , Bakker M , van Gils M J , Dol L , Geerlings S E , Goorhuis A , Hovius J W R , Nellen F J B , Prins J M , van der Poll T , van der Valk M , Wiersinga W J , van Vugt M , de Bree G , Lemkes B A , Spoorenberg V , Wit F W N M , van Eden J , Pijnappel F J J , Weijsenfeld A , Smalhout S , van den Bout I J Hylkema , Bruins C , Spelbrink M E , Postema P G , Bisschop P H L T , Dekker E , van der Velde N , Franssen R , Willemsen J M R , Vogt L , Portegies P , Geurtsen G J , Visser I , Schadé A , Nieuwkerk P T , van Steenwijk R P , Jonkers R E , Majoie C B L M , Caan M W A , van den Born B J H , Stroes E S G , van Oorspronk S 
Published: December 2024

Abstract

Background
People with HIV (PWH) experience a higher burden of aging-associated comorbidities, the underlying mechanisms of which remain to be fully elucidated. We aimed to identify profiles based on immune, inflammatory, and aging biomarkers in blood from PWH and controls, and explore their association with total comorbidities over time.

Methods
Latent profile analysis was used to construct biomarker profiles in AGEhIV cohort participants (94 with well-controlled HIV on antiretroviral therapy [ART] and 95 controls without HIV) using baseline measurements of selected biomarkers. Factors associated with profile membership were assessed by multivariable logistic regression. The association between profiles and mean total comorbidities during follow-up was assessed by Poisson regression, stratified by HIV status. Comorbidities included type 2 diabetes, non-AIDS malignancies, cardiovascular disease, osteoporosis, chronic kidney disease. and frailty.

Results
Three biomarker profiles were identified: “high thymic output/low inflammation” (HT/LI) profile (n = 27 PWH, n = 9 controls), “low thymic output/high inflammation” (LT/HI) profile (n = 29 PWH, n = 26 controls), and an “intermediate” profile (n = 38 PWH, n = 60 controls). Only HIV status was significantly associated with profile membership. PWH, relative to controls, more often exhibited the HT/LI profile compared to other profiles. In PWH, but not in controls, the HT/LI profile was associated with significantly lower mean comorbidities during a median 8.0 years (interquartile range, 7.1–8.1) of follow-up.

Conclusions
People aging with well-controlled HIV on ART were more likely to exhibit a biomarker profile indicative of preserved thymic function and less chronic inflammation compared to controls. PWH with such a profile seemed relatively protected from developing aging-associated comorbidities.

Clinical Trials Registration
NCT01466582.