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 HIV- (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 HIV- 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.
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 HIV- (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 HIV- 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.
Authors: Deborah L Regidor; Roger Detels; Elizabeth C Breen; Daniel P Widney; Lisa P Jacobson; Frank Palella; Charles R Rinaldo; Jay H Bream; Otoniel Martínez-Maza Journal: AIDS Date: 2011-01-28 Impact factor: 4.177
Authors: Shailja Shah; Yifei Ma; Rebecca Scherzer; Greg Huhn; Audrey L French; Michael Plankey; Marion G Peters; Carl Grunfeld; Phyllis C Tien Journal: AIDS Date: 2015-07-17 Impact factor: 4.177
Authors: L P Fried; C M Tangen; J Walston; A B Newman; C Hirsch; J Gottdiener; T Seeman; R Tracy; W J Kop; G Burke; M A McBurnie Journal: J Gerontol A Biol Sci Med Sci Date: 2001-03 Impact factor: 6.053
Authors: Thomas D Brothers; Susan Kirkland; Giovanni Guaraldi; Julian Falutz; Olga Theou; B Lynn Johnston; Kenneth Rockwood Journal: J Infect Dis Date: 2014-06-05 Impact factor: 5.226
Authors: Damani A Piggott; Ravi Varadhan; Shruti H Mehta; Todd T Brown; Huifen Li; Jeremy D Walston; Sean X Leng; Gregory D Kirk Journal: J Gerontol A Biol Sci Med Sci Date: 2015-09-18 Impact factor: 6.053
Authors: Abbe N Vallejo; David L Hamel; Robert G Mueller; Diane G Ives; Joshua J Michel; Robert M Boudreau; Anne B Newman Journal: PLoS One Date: 2011-10-20 Impact factor: 3.240
Authors: Julian J Weiss; Laura Sanchez; Jane Hubbard; Janet Lo; Steven K Grinspoon; Kathleen V Fitch Journal: J Nutr Date: 2019-01-01 Impact factor: 4.798
Authors: Kellie L Hawkins; Long Zhang; Derek K Ng; Keri N Althoff; Frank J Palella; Lawrence A Kingsley; Lisa P Jacobson; Joseph B Margolick; Jordan E Lake; Todd T Brown; Kristine M Erlandson Journal: AIDS Date: 2018-06-19 Impact factor: 4.177
Authors: Joseph B Margolick; Jay H Bream; Tricia L Nilles; Huifen Li; Susan J Langan; Shane Deng; Ruibin Wang; Nikolas Wada; Sean X Leng Journal: J Infect Dis Date: 2018-06-20 Impact factor: 5.226
Authors: Martin Tibuakuu; Di Zhao; Ankita Saxena; Todd T Brown; Lisa P Jacobson; Frank J Palella; Mallory D Witt; Susan L Koletar; Joseph B Margolick; Eliseo Guallar; Sai Krishna C Korada; Matthew J Budoff; Wendy S Post; Erin D Michos Journal: J Cardiovasc Comput Tomogr Date: 2018-01-31
Authors: Sai Krishna C Korada; Di Zhao; Martin Tibuakuu; Todd T Brown; Lisa P Jacobson; Eliseo Guallar; Robert K Bolan; Frank J Palella; Joseph B Margolick; Jeremy J Martinson; Matthew J Budoff; Wendy S Post; Erin D Michos Journal: Atherosclerosis Date: 2017-08-26 Impact factor: 5.162