TY - JOUR
T1 - Frailty and circulating markers of inflammation in HIV+ and HIV2 men in the multicenter AIDS cohort study
AU - Margolick, Joseph B.
AU - Bream, Jay H.
AU - Martínez-Maza, Otoniel
AU - Lopez, Joe
AU - Li, Xiuhong
AU - Phair, John P.
AU - Koletar, Susan L.
AU - Jacobson, Lisa P.
N1 - Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Background: Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known. Methods: We analyzed 24 serologic biomarkers of monocyte, T-cell, or B-cell activation in HIV2 (n = 207) and HIV+ (n = 714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study (MACS) and were classified as frail or nonfrail according to expression or nonexpression of the frailty phenotype at 2 consecutive study visits. Results: After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (P < 0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (P = 0.003). After further adjustment for body mass index (BMI), smoking, and comorbidities, only the association with C-reactive protein was significant at P , 0.002, with levels approximately 50% higher in frail compared with nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV2 men, none of these markers differed significantly by frailty. Conclusions: These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/ macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, C-reactive protein, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.
AB - Background: Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known. Methods: We analyzed 24 serologic biomarkers of monocyte, T-cell, or B-cell activation in HIV2 (n = 207) and HIV+ (n = 714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study (MACS) and were classified as frail or nonfrail according to expression or nonexpression of the frailty phenotype at 2 consecutive study visits. Results: After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (P < 0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (P = 0.003). After further adjustment for body mass index (BMI), smoking, and comorbidities, only the association with C-reactive protein was significant at P , 0.002, with levels approximately 50% higher in frail compared with nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV2 men, none of these markers differed significantly by frailty. Conclusions: These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/ macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, C-reactive protein, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.
KW - C-reactive protein
KW - HIV
KW - chemokines
KW - cohort study
KW - cytokines
KW - frailty
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U2 - 10.1097/QAI.0000000000001261
DO - 10.1097/QAI.0000000000001261
M3 - Article
C2 - 28225718
AN - SCOPUS:85015854304
SN - 1525-4135
VL - 74
SP - 407
EP - 417
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 4
ER -