icon-folder.gif   Conference Reports for NATAP  
  ICAAC 2014 54th Interscience Conference
on Antimicrobial Agents and Chemotherapy
September 5-9, 2014, Washington, DC
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CD8-Cell Activation, Senescence, Osteoprotegerin Tied to Atherosclerosis in Italian HIV Cohort....
(from jules: senescence marker higher in HIV+ & senescence marker associated with heart disease)

  ICAAC 2014. September 5-9, 2014. Washington, DC
Mark Mascolini
Immune activation, immune senescence, and the soluble marker osteoprotegerin were all linked to higher carotid artery intima media thickness (cIMT) in a cross-sectional study of HIV-positive people with viral suppression and matched HIV-negative controls [1]. The association with osteoprotegerin fell short of statistical significance.
Ongoing immune activation in HIV-positive people with an undetectable viral load may contribute to a heightened risk of atherosclerosis. Osteoprotegerin protects bones from excessive resorption [2]. Some research also links osteoprotegerin to atherosclerosis in people with HIV [3], while other research does not [4]. To pursue potential links between immune activation, immune senescence, osteoprotegerin, and atherosclerosis in antiretroviral-treated people with an undetectable HIV load, researchers at Rome's Sapienza University conducted this cross-sectional comparison.
The study involved 94 antiretroviral-treated adults with an undetectable viral load and a Framingham cardiovascular risk score below 10%. Researchers matched them by age, gender, and Framingham score to 24 HIV-negative people. All study participants had ultrasound-determined cIMT. The investigators assessed smoking status, family history of cardiovascular disease, and other relevant variables. They determined CD4- and CD8-cell activation by evaluating cells for expression of CD38 and HLA-DR. Immune senescence markers were CD28 and CD57. The researchers used ELISA to measure osteoprotegerin levels.
HIV-positive people averaged 47.4 years in age (+/- 11). Compared with HIV-negative controls, people with HIV had significantly greater (worse) average cIMT (0.85 versus 0.28 mm, P < 0.001). cIMT was pathological (at or above 0.9 mm) in 42 of 94 people with HIV (45%).
Osteoprotegerin levels in plasma were significantly higher in participants with than without HIV (6.59 versus 3.57 pmol/L, P < 0.001), as were levels of activated CD8 cells and senescent CD8 cells (P < 0.001). Study participants with pathologically elevated cIMT had significantly higher levels of activated CD8 cells (P = 0.048), senescent CD8 cells (P < 0.001), and osteoprotegerin (P = 0.053) than did people with normal cIMT.
Multivariate analysis identified three independent predictors of pathologically elevated cIMT: older age, CD8-cell activation, and CD8-cell senescence, at the following adjusted odds ratios (aOR) (and 95% confidence intervals):
-- Older age: aOR 1.202 (95% CI 1.080 to 1.338), P < 0.001
-- CD8-cell activation: aOR 1.801 (95% CI 1.079 to 3.005), P = 0.024
-- CD8-cell senescence: aOR 1.408 (95% CI 1.143 to 1.734), P < 0.001
Osteoprotegerin levels did not predict pathologically elevated cIMT in this analysis (aOR 1.082, 95% CI 0.900 to 1.302, P = 0.397).
The Sapienza University team proposed that "immune activation and immunosenescence of CD8 T cells together with osteoprotegerin plasma levels might contribute to development and progression of early atherosclerosis," even in antiretroviral-treated people with an undetectable viral load.
1. D'Abramo A, Zingaropoli MS, Oliva A, et al. HIV infection and atherosclerosis: role of immune activation, immunesenescence and osteoprotegerin. ICAAC 2014. September 5-9, 2014. Washington, DC. Abstract H-1645.
2. Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007;9 Suppl 1:S1.
3. D'Abramo A, D'Agostino C, Oliva A, et al. Early atherosclerosis in HIV infected subjects on suppressive antiretroviral treatment: role of osteoprotegerin. ISRN AIDS. 2013;2013:737083. http://www.hindawi.com/journals/isrn/2013/737083/
4. Kelesidis T, Kendall MA, Yang OO, Hodis H, Currier JS. Perturbations of circulating levels of RANKL-osteoprotegerin axis in relation to lipids and progression of atherosclerosis in HIV-infected and -uninfected adults: ACTG NWCS 332/A5078 Study. AIDS Res Hum Retroviruses. 2013;29:938-948. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653400/


"......c-IMT was higher in HIV+ than in controls (0.85 ± 0.17 mm vs 0.28 ± 0.24 mm, p<0,001) (Fig.1). ........CD8+ T-cell activation (CD38+/HLADR+) and senescence (CD28-/CD57+) were higher in HIV+ patients than controls (p<0.001) (Fig. 3A and B). ......Subjects with pathological c-IMT exhibited higher activated CD8+ CD38+HLADR+ (p=0.048), CD8+ CD28-CD57+ (p<0.001) (Fig. 3C and D) and OPG (p=0.053) (Fig.2B) than subjects with normal c-IMT......"