![]() Phlebotomy was performed at enrollment, and plasma specimens cryopreserved. 18, 19, 28 Intermediate-stage AMD was graded at the reading center as previously described. Computer software measured the caliber of the individual vessels, then combined them into two summary measures: the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE). Briefly, the six largest arterioles and six largest venules in a ring-shaped area located between 0.5 and 1.0 disc diameters from the edge of the optic nerve were identified. Retinal vascular indices were determined using previously-described semi-automated methods. 18, 19, 28 As part of a study of AMD, mortality, and biomarkers of systemic inflammation, participants with AMD at enrollment were matched on decade of age, race/ethnicity-, and sex with 2 controls from LSOCA for a case control study, 29 resulting in a study population of 454 persons with AIDS. 27 Baseline photographs were taken on all participants and evaluated for retinal vascular caliber at the Reading Center in the Department of Ophthalmology and Visual Sciences at the University of Wisconsin, Madison, School of Medicine and Public Health by graders masked as to clinical data, as previously described. The Longitudinal Study of the Complications of AIDS was a prospective cohort study of patients with the acquired immunodeficiency syndrome conducted in the era of modern ART. Therefore, we evaluated the relationship between several biomarkers of systemic inflammation and retinal vascular caliber in persons with AIDS enrolled in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA). 20 – 24 Elevated blood levels of C-reactive protein (CRP) a biomarker of systemic inflammation, are a risk factor for the development of AMD in HIV-uninfected persons, 25 and persons with AMD have elevated blood levels of several proinflammatory cytokines, 26 suggesting that systemic inflammation might be a common pathogenetic factor in both processes. ![]() 19 Retinal venular dilation is associated with systemic inflammation in HIV-uninfected persons. 18 Although a decline in retinal vascular caliber is associated with increasing age, persons with AIDS and AMD have dilated retinal arterioles and venules compared to persons with AIDS without AMD. 17 Retinal vascular caliber declines with age, and persons with AIDS have retinal arteriolar and venular calibers comparable to HIV-uninfected persons ∼10 years older. 13 – 15Ĭonsistent with this accentuated/accelerated aging, persons with AIDS have an ∼4-fold increased age- and sex-adjusted prevalence of intermediate-stage AMD compared to HIV-uninfected persons 16 and a ∼1.75-fold increased race/ethnicity- and sex-adjusted incidence of intermediate-stage AMD compared to HIV-uninfected persons. 9 – 12 Compared to HIV-uninfected persons, those with HIV infection have persistently high levels of immune activation and systemic inflammation, despite ART-mediated viral suppression, particularly those who initiate ART at advanced stages of HIV disease. 9, 10 They also exhibit features of immunosenescence, a state characterized by chronic immune activation and systemic inflammation, but a poor response to new antigenic challenges. 5, 6 They have an increase is age-related diseases such as cardiovascular disease, metabolic disorders (e.g., diabetes and osteoporosis), neurocognitive decline, and age-related cancers not associated with AIDS, 7 – 10 suggesting accentuated and accelerated aging. 1 – 4 Nevertheless, they have a shortened lifespan compared to comparably aged HIV-uninfected persons, largely due to age-related diseases. Human immunodeficiency virus (HIV)-infected persons treated with modern antiretroviral therapy (ART) have suppressed HIV replication, reduced amounts of HIV RNA circulating in the blood (HIV viral load), improved immune function typically manifested as a rise in CD4+ T cells (immune recovery), decreased opportunistic infections, and an improved lifespan.
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