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COBRA/Europe-Aging Epidemic/ Increased Brain Aging in HIV+
  Aging Epidemic - Comorbidities WK 2016, NYC (Guaraldi G, De Francesco), : 20% are currently experiencing falls....20% currently disabled due to frailty - percent & numbers will increase every year [see graph] ..... .....60% currently frail & 75% frail by 2030 - Future challenges for clinical care of an ageing population infected with HIV: a "geriatric-HIV" modelling study - [Healthcare Costs].... Very Sobering Analysis on Aging in HIV+....60% frail....http://www.natap.org/2016/AdverseReactComor/AdverseReactComor_13.htm
COBRA - Increased brain-predicted aging in treated HIV disease: controls (n = 105) were recruited from 2 sites, London and Amsterdam as part of the Comorbidity in Relation to AIDS (COBRA) collaboration.....average age was 56 (50-62)....We observed lower brain volumes in HIV-positive individuals, presumably due to atrophy" http://www.natap.org/2017/HIV/092217_02.htm
Objective:To establish whether HIV disease is associated with abnormal levels of age-relatedbrain atrophy, by estimating apparent brain age using neuroimaging and exploring whether theseestimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters.
Methods:A large sample of virologically suppressed HIV-positive adults (n5162, age 45-82years) and highly comparable HIV-negative controls (n5105) were recruited as part of the Co-morbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n52,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used toestimate brain-predicted age; then brain-predicted age difference (brain-PAD5brain-predictedbrain age2chronological age) scores were calculated. Neuropsychological and clinical assess-ments were also carried out.
Results:HIV-positive individuals had greater brain-PAD score (mean6SD 2.1567.79 years)compared to HIV-negative individuals (20.8768.40 years;b53.48,p,0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (informa-tion processing speed, executive function, memory) and general cognitive performance across allparticipants. Brain-PAD score was not associated with age, duration of HIV infection, or otherHIV-related measures.
Conclusion:Increased apparent brain aging, predicted using neuroimaging, was observed inHIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increasedapparent brain aging related to cognitive deficits. However, predicted brain age difference did notcorrelate with chronological age or duration of HIV infection, suggesting that HIV disease mayaccentuate rather than accelerate brain aging.Neurology®2017;88:1349-1357
Do people living with HIV experience greater age advancement than their HIV-negative counterparts? Yes-Biological Age greater by 13 Years in HIV+ /
Co-morBidity in Relation to AIDS (COBRA) Collaboration
In conclusion, our results suggest that PLWH with undetectable plasma HIV RNA may experience accentuated aging compared with HIV-negative individuals with similar lifestyles, as estimated using a set of validated biomarkers of aging. This age advancement appears to be related to viral co-infections such as CMV and chronic HBV, but also to historic severe immunosuppression and possibly exposure to particular antiretroviral drugs. Future longitudinal studies are required to further help clarifying the effect of HIV and its treatment on the natural aging process and the functional and clinical consequences in the millions of PLWH worldwide.
Objectives: Despite successful antiretroviral therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.
Design: Cross-sectional analysis of 134 PLWH on suppressive antiretroviral therapy, 79 lifestyle-comparable HIV-negative controls aged 45 years or older from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors.
Methods: Biological age was estimated using a validated algorithm based on 10 biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression.
Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6-14.9) years] and HIV-negative [5.5 (3.8-7.2) years] COBRA participants compared with blood donors [-7.0 (-4.1 to -9.9) years, both P's < 0.001)], but also in HIV-positive compared with HIV-negative participants (P < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1-6.8) years among those with nadir CD4+ T-cell count less than 200 cells/μl and by 0.1 (0.06-0.2) years for each additional month of exposure to saquinavir.
Conclusion: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared with blood donors, to which persistent CMV, HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure.
Whilst both groups of COBRA participants exhibitedage advancement, this was significantly greater in HIV-positive than in HIV-negative participants. Whilst thisdifference in age advancement did not appear to beexplained by differences in participant characteristics,chronic viral co-infections such as CMV and HBV,prior immunosuppression and exposure to someantiretroviral drugs may have contributed to this ageadvancement. CMV and HBV co-infections may causepremature aging of the immune system in PLWH bytheir chronic antigenic stimulation, inducing systemicimmune activation [28].
Associations with HIV parameters and exposure to antiretroviral drugs
Among the HIV-positive participants in COBRA, in univariable regression analyses, positive correlations were found between age advancement and time since HIV diagnosis, duration of antiretroviral therapy and nadir CD4 T-cell count <200 cells/ml (Table 3). Cumulative exposure and/or prior exposure to some antiretroviral drugs was also associated with an increased age advancement (Supplementary Table 4, http://links.lww.- com/QAD/B389); in particular each additional year of exposure to saquinavir was associated with a 1.39 (95% CI 0.71-2.07) years increase in age advancement (P<0.001), but also prior exposure to stavudine or any d-drug were associated with greater age advancement (P=0.02 and P=0.03, respectively). Due to the strong correlations between these factors, we ran a multivariable regression analysis with all HIV-parameters and exposures to antiretroviral drugs that were significantly associated with age advancement in univariable analysis (P<0.1), also accounting for chronic HBV, total anti-CMV IgG antibody titer and CD8 T-cell count. In this multivariable analysis, only cumulative exposure to saquinavir (average increase of 1.17 (0.49, 1.85) years per year of exposure,P<0.001) and nadir CD4 T-cell count lessthan 200 cells/ml (average increase of 3.00 (_0.22 to 6.22)years,P¼0.07), as well as chronic HBV (7.35 (0.42-14.29) years,P¼0.04) and total anti-CMV IgG antibodytiter (1.86 (0.22-3.51) years per one log increase,P¼0.03), retained their significant associations.

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