HIV and Inflamm-Aging: How Do We Reach the Summit of Healthy Aging?

Abstract

People with HIV (PWH) are living longer and experiencing a greater burden of morbidity from non-AIDS-defining conditions. Chronically treated HIV disease is associated with ongoing systemic inflammation that contributes to the development of chronic conditions (eg, cardiovascular disease) and geriatric syndromes (eg, frailty). Apart from HIV disease, a progressive increase in systemic inflammation is a characteristic feature of biologic aging, a process described as "inflammaging." Inflamm-aging is driven by persistent antigen stimulation and stress, leading to an immune profile characterized by elevated levels of blood inflammatory markers and cellular activation and senescence. Chronic HIV disease is hypothesized to accentuate the immune profile of inflamm-aging, in part through viral persistence in lymphatic tissues, permanent injury impairing immune recovery, the presence of copathogens, gut dysbiosis and microbial translocation, and chromosomal and genetic alterations associated with immune activation. Few strategies exist for safe and effective modulation of systemic inflammation among older PWH. The strongest current evidence supports aggressive management of modifiable risk factors such as lipids, blood pressure, and levels of physical activity. Future inflamm-aging research should be directed toward advancing the implementation of proven approaches, such as physical activity, as well as studying novel mechanisms of, and treatments for, inflamm-aging among PWH.

Figure 1.

Proinflammatory Tone and Age-Related Disease Risk. Schematic model of inflamm-aging, disease risk, and the influence of HIV. With normal physiologic aging, there is a progressive increase in proinflammatory tone that results from the summation of chronic stimulation and stress with impaired resolution of inflammatory responses. Over time, this process of “inflamm-aging” is associated with the onset of age-related diseases, which then further increase inflammatory tone and additional disease risk resulting in multimorbidity and age-related phenotypes (eg, frailty). HIV disease accentuates this process, the immune profile of inflamm-aging, and ultimately risk for age-related morbidity. Adapted from Franceschi et al.

Figure 2.

Healthy Aging Focuses on Healthy Life Expectancy. Schematic model of healthy life expectancy and life expectancy. Inflamm-aging is associated with increased morbidity among people with HIV (PWH). Aging research is increasingly focused on the promotion of healthy life expectancy (years lived in good health) in addition to the extension of overall life expectancy. Healthy aging interventions have the potential to increase life expectancy and healthy life expectancy, or importantly, may increase healthy life expectancy more than overall life expectancy, thus compressing the period of morbidity in later life. Treatment of inflamm-aging is likely to be an important component of the promotion of healthy life expectancy and compression of morbidity for PWH. Adapted from Fries et al and Seals et al.