HIV infection is associated with the premature onset of age-associated co-morbidities such as non-AIDS malignancies and cardiovascular disease. These co-morbidities have been linked to persistently elevated serum levels of proinflammatory cytokines that mimic an aging phenotype known as "inflamm-aging." In both middle-aged HIV+ persons and older HIV seronegative adults, inflamm-aging is associated with more limited T cell repertoires and increased risk for morbidities and mortality. Our hypothesis is that inflamm-aging is responsible for the premature immune senescence associated with HIV infection in aging individuals. Immune senescence, characterized by diminished replicative capacity, has been observed in middle-aged persons treated with highly active antiretroviral therapy (H/VKRT) who achieve immune reconstitution and undetectable viral loads. Senescent cells are characterized bythe absence ofthe surface marker CD28, and in advanced senescence express CD57 (CD28-/CD57+ phenotype). Fish oil may be an effective treatment option for reducing HIV-related inflamm-aging. Cold water fish are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have anti-inflammatory effects.. We propose a 12-week, randomized, double-blind, placebo-controlled trial to explore the safety and estimate the effect size of fish oil to modulate parameters of inflamm-aging and immune senescence in a well-characterized cohort of 38 HIV+ AA. Participants will be between the ages of 50 and 65, on stable H/ ART, and with inflammation evidenced by elevated plasma concentrations of interleukln-6 (IL-6) or high sensitivity C-reactive protein (hsCRP). Participants will be recruited from the Rush Center of Excellence on Disparities in HIV and Aging (Rush CEDHA). Each participant will be randomized to receive either 1.2 grams daily of EPA and DHA (600 mg of EPA and 600 mg of DHA), or a placebo identical in appearance for 12 weeks. We will measure (a) soluble markers of inflammation: TNF-alpha, lL-6, and gamma IFN;and (b) markers of immune senescence: CD28 and CD57 expression on CD8+ and CD4+ T lymphocyte cells. At baseline and 4 and 12 weeks post-baseline, we will measure safety parameters.

Public Health Relevance

HIV infection is associated with chronic inflammation which can lead to the premature onset of immune aging in middle aged persons. Immune aging can lead to the development of chronic conditions, such as heart disease and cancer. Treatments that reduce inflammation have the potential to reverse immune aging. We propose to test fish oil, a known anti-inflammatory, to reverse immune aging in HIV+ persons.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD006886-03
Application #
8609516
Study Section
Special Emphasis Panel (ZMD1-RN)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
3
Fiscal Year
2014
Total Cost
$160,520
Indirect Cost
$41,328
Name
Rush University Medical Center
Department
Type
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Turner, Arlener D; Capuano, Ana W; Wilson, Robert S et al. (2015) Depressive symptoms and cognitive decline in older african americans: two scales and their factors. Am J Geriatr Psychiatry 23:568-78
Barnes, Lisa L; Bennett, David A (2014) Alzheimer's disease in African Americans: risk factors and challenges for the future. Health Aff (Millwood) 33:580-6
Rajan, Kumar B; Wilson, Robert S; Skarupski, Kimberly A et al. (2014) Gene-behavior interaction of depressive symptoms and the apolipoprotein E {varepsilon}4 allele on cognitive decline. Psychosom Med 76:101-8
Fleischman, Debra A; Leurgans, Sue; Arfanakis, Konstantinos et al. (2014) Gray-matter macrostructure in cognitively healthy older persons: associations with age and cognition. Brain Struct Funct 219:2029-49
Tangney, Christy C; Li, Hong; Wang, Yamin et al. (2014) Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons. Neurology 83:1410-6
James, Bryan D; Leurgans, Sue E; Hebert, Liesi E et al. (2014) Contribution of Alzheimer disease to mortality in the United States. Neurology 82:1045-50
Arfanakis, Konstantinos; Fleischman, Debra A; Grisot, Giorgia et al. (2013) Systemic inflammation in non-demented elderly human subjects: brain microstructure and cognition. PLoS One 8:e73107