Pierre Duffau1,2, Alexandra Ozanne3, Fabrice Bonnet3,4, Estibaliz Lazaro1,5, Charles Cazanave6, Patrick Blanco1,7, Etienne Rivière5, Arnaud Desclaux6, Caroline Hyernard1, Noemie Gensous2, I Pellegrin3,7, L Wittkop3,8. 1. CNRS-UMR 5164, Immuno ConcEpT, Bordeaux University and Bordeaux Hospital. 2. CHU de Bordeaux, Service de Médecine Interne et Immunologie Clinique. 3. University Bordeaux, ISPED, Inserm, Bordeaux Population Health Research Center, Team MORPH3EUS, UMR 1219, CIC-EC 1401. 4. CHU de Bordeaux, Service de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, Bordeaux. 5. CHU de Bordeaux, Service de Médecine Interne et Maladies infectieuses, Hôpital Haut-Lévêque, Pessac. 6. CHU de Bordeaux, Service de Maladies Infectieuses et Tropicales. 7. CHU de Bordeaux, Laboratoire d'Immunologie et Immunogénétique, University Bordeaux. 8. CHU de Bordeaux, Pôle de santé publique, Bordeaux, France.
Abstract
BACKGROUND: The widespread introduction of combination antiretroviral therapy (cART) has increased survival of HIV-infected patients. However, the prevalence of age-related comorbidities remains higher than that of the general population, suggesting that individuals with HIV suffer from accelerated aging. Immune activation, senescence and inflammation could play an important role in this process. METHODS: The CIADIS (Chronic Immune Activation anD Senescence) sub-study analyzed biomarkers of activation, differentiation and senescence of T cells in a cellular-CIADIS-weighted score, whereas biomarkers of inflammation were analyzed in a soluble CIADIS-weighted score using principal component analysis. Adjusted logistic regression and Cox proportional hazard models were used to determine the association between CIADIS-weighted scores and the presence of multimorbidity, time to occurrence of the first new age-related comorbidity and time to death, over a 3-year follow-up period. RESULTS: Of 828 patients with an undetectable viral load, a higher cellular-CIADIS-weighted score and higher TNFRI levels were independently associated with the presence of multimorbidity (OR 1.3; 95% CI 1.0-1.6; P = 0.02), but the soluble CIADIS-weighted score was not (OR = 1.1; 95% CI 0.9-1.3; P = 0.33). A higher cellular CIADIS-weighted score (hazard ratio 2.2; P < 0.01), higher levels of CD8 activation and a lower CD4/CD8 ratio were associated with a higher risk of age-related comorbidities. Only TNFRI was associated with mortality in a 3-year period. CONCLUSION: The cellular CIADIS-weighted score was independently associated with both multimorbidity at inclusion and the risk of new age-related comorbidity during a 3- year follow-up. TNFRI was associated a higher risk for mortality.
BACKGROUND: The widespread introduction of combination antiretroviral therapy (cART) has increased survival of HIV-infectedpatients. However, the prevalence of age-related comorbidities remains higher than that of the general population, suggesting that individuals with HIV suffer from accelerated aging. Immune activation, senescence and inflammation could play an important role in this process. METHODS: The CIADIS (Chronic Immune Activation anD Senescence) sub-study analyzed biomarkers of activation, differentiation and senescence of T cells in a cellular-CIADIS-weighted score, whereas biomarkers of inflammation were analyzed in a soluble CIADIS-weighted score using principal component analysis. Adjusted logistic regression and Cox proportional hazard models were used to determine the association between CIADIS-weighted scores and the presence of multimorbidity, time to occurrence of the first new age-related comorbidity and time to death, over a 3-year follow-up period. RESULTS: Of 828 patients with an undetectable viral load, a higher cellular-CIADIS-weighted score and higher TNFRI levels were independently associated with the presence of multimorbidity (OR 1.3; 95% CI 1.0-1.6; P = 0.02), but the soluble CIADIS-weighted score was not (OR = 1.1; 95% CI 0.9-1.3; P = 0.33). A higher cellular CIADIS-weighted score (hazard ratio 2.2; P < 0.01), higher levels of CD8 activation and a lower CD4/CD8 ratio were associated with a higher risk of age-related comorbidities. Only TNFRI was associated with mortality in a 3-year period. CONCLUSION: The cellular CIADIS-weighted score was independently associated with both multimorbidity at inclusion and the risk of new age-related comorbidity during a 3- year follow-up. TNFRI was associated a higher risk for mortality.
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