Abstract

As individuals with human immunodeficiency virus (HIV) infection live longer, aging and age-related chronic conditions have become major health concerns for this vulnerable population. Substantial evidence suggests that chronic inflammation and immune activation contribute significantly to chronic conditions in people aging with or without HIV infection. As a result, increasing numbers of inflammation and immune activation biomediators have been measured. While very few studies describe their in vivo relationships, such studies can serve as an important and necessary initial step toward delineating the complex network of chronic inflammation and immune activation. In this study, we evaluated in vivo relationships between serum levels of neopterin, a biomediator of immune activation, and four commonly described inflammatory biomediators: soluble tumor necrosis factor (TNF)-α receptor (sTNFR)-1, sTNFR-2, interleukin (IL)-6, and C-reactive protein (CRP), as well as the impact of HIV infection and aging in the AIDS Linked to the Intravenous Experience (ALIVE) study, a community-recruited observational study of former and current injection drug users (IDUs) with or at high risk for HIV infection in Baltimore, MD, USA. The study included 1,178 participants in total with 316 HIV-infected (HV+) and 862 HIV-uninfected (HIV−) IDUs. Multivariate regression analyses were employed, adjusting for age, sex, body mass index, smoking, hepatitis C virus co-infection, injection drug use, comorbidities, and HIV status (for all participants), and HIV viral load, CD4+ T-cell counts, and antiretroviral therapy (for HIV+ participants). The results showed significant impact of aging on all five biomediators and that of HIV infection on all but sTNFR-1. In the adjusted model, neopterin had positive associations with sTNFR-1 and sTNFR-2 (partial correlation coefficients: 0.269 and 0.422, respectively, for all participants; 0.292 and 0.354 for HIV+; and 0.262 and 0.435 for HIV−, all p < 0.0001). No significant associations between neopterin and IL-6 or CRP were identified. Such differential relationships between circulating neopterin and sTNFR-1, sTNFR-2, IL-6, and CRP may help inform their selection in future studies. These findings may also facilitate elucidation of underlying inflammatory and immune activation pathways that contribute to age-related chronic conditions, potentially leading to identification of key biomediators, particularly those upstream of CRP, as novel targets for intervention.

Highlights

  • Human immunodeficiency virus (HIV) infection remains a major health problem worldwide

  • One possible explanation for such preferential associations is that monocytes and macrophages are a main source of neopterin, sTNFR-1 and sTNFR-2 production

  • IL-6 is considered as a monokine and no consistent association was observed between neopterin and IL-6 levels

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Summary

Introduction

Human immunodeficiency virus (HIV) infection remains a major health problem worldwide. As effective treatment is available through combination antiretroviral therapy (cART) and new infections have increased among older adults, the number of older individuals living with HIV has risen dramatically over the past decade . As HIV-infected (HIV+) individuals live longer, age-related chronic conditions commonly encountered in the geriatric population, some of which are termed HIVassociated non-AIDS conditions, have become major health concerns for this vulnerable aging population despite suppression of HIV viral load to clinically undetectable levels by cART [3,4,5,6]. While much remains to be learned, it is believed that age-related senescent remodeling of the immune system, or immunosenescence, contributes significantly to the development of such chronic conditions and adverse health outcomes, and that HIV infection appears to accelerate immunosenescence [6,7,8,9]

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