Biomarkers of Activation and Inflammation to Track Disparity in Chronological and Physiological Age of People Living With HIV on Combination Antiretroviral Therapy

Abstract

With advancement, prompt use, and increasing accessibility of antiretroviral therapy, people with HIV are living longer and have comparable lifespans to those negative for HIV. However, people living with HIV experience tradeoffs with quality of life often developing age-associated co-morbid conditions such as cancers, cardiovascular diseases, or neurodegeneration due to chronic immune activation and inflammation. This creates a discrepancy in chronological and physiological age, with HIV-infected individuals appearing older than they are, and in some contexts ART-associated toxicity exacerbates this gap. The complexity of the accelerated aging process in the context of HIV-infection highlights the need for greater understanding of biomarkers involved. In this review, we discuss markers identified in different anatomical sites of the body including periphery, brain, and gut, as well as markers related to DNA that may serve as reliable predictors of accelerated aging in HIV infected individuals as it relates to inflammatory state and immune activation.

Multicomponent physical activity program to prevent body changes and metabolic disturbances associated with antiretroviral therapy and improve quality of life of people living with HIV: a pragmatic trial

“…To our knowledge, this is the first clinical trial designed to evaluate the effectiveness of PA in preventing body changes and metabolic disturbances associated with HIV infection and ART. Previous intervention studies have addressed the impact of PA in PLH, including those who already presented with body changes or metabolic disturbances ( 11 - 13 ). Furthermore, our approach has been designed as a multicomponent intervention program, including cardiorespiratory and strength training, in parallel with educational sessions to promote the PA.…”

“…Furthermore, elevated blood concentrations of inflammatory biomarkers, such as IL-6, IL-8, IL-15, and TNF-α, have been reported in PLH ( 9 - 10 ). Altogether, chronic immune activation, inflammation, and metabolic alterations are believed to contribute to the development of age-related diseases (liver dysfunction, neurological decline) and atherosclerosis in PLH, ultimately leading to enhanced cardiovascular risk ( 10 , 11 ).…”

The Contributions of Clinical Pharmacology to HIV Cure Research

“…ATI, however, comes with several limitations. These include development of acute retroviral syndrome with symptoms of fatigue, high‐grade fever, and enlarged peripheral LNs, among others, that may lead to multi‐organ failure, expansion of viral reservoirs, the appearance of minor quasi‐species of drug‐resistant variants, an increase in chances of transmission of HIV to sero‐discordant partners, and an exaggeration of HIV‐associated chronic inflammation/immune activation, which increases the risk of non‐AIDS related illness like premature aging, atherosclerosis, cardiovascular diseases, neurological disorders, and osteoporosis 27,28 …”

Dissecting drivers of immune activation in chronic HIV-1 infection

“…7À10 While the root drivers of this inflammatory state are incompletely characterized, it is possible that low level viral replication in the HIV reservoir, coinfections, and microbial translocation may contribute to this inflammatory state. 11,12 However, less well studied are other factors such as gender, local environmental factors, and nutrition that may contribute to low level immune activation, bias other scientific findings, and impact mortality and morbidity of PLWH.…”