Systemic inflammation and risk of age-associated diseases in people living with HIV on long term suppressive antiretroviral therapy

Abstract

Objective(s):To assess the levels of systemic inflammatory markers of age-associated comorbidities in people living with HIV (PLHIV) on long term suppressive antiretroviral therapy (ART). Design:Prospective cross-sectional study in a well-defined Indian cohort of PLHIV.Methods: Blood samples were obtained from therapy naïve PLHIV (Pre-ART, n=43), PLHIV on ART for >5 years (ART, n=53), and HIV-negative healthy controls (HIVNC, n=41).Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, telomere length and HIV-1 reservoir. Results:Despite a median duration of eight years of successful ART, sCD14 (p<0.001) and sCD163 (p=0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Besides, eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL and TRANCE, were found to be significantly different (p<0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation.Linear regression analysis showed a significant negative association between HIV-1positivity and telomere length (p<0.0001). in ART-group CXCL1 (p=0.048) and TGF-α (p=0.026) have a significant association with increased telomere length and IL-10RA was significantly associated with decreased telomere length (p=0.042). Conclusions:The study identified several candidate biomarkers of age-related pre-mature aging in PLHIV on successful ART in a standardized public-health setting. This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.

Pathogenesis of Aging and Age-related Comorbidities in People with HIV: Highlights from the HIV ACTION Workshop

“…Other contributing factors that may promote biological aging and age-related comorbidities in HIV include antigen-driven proliferation, shortening of telomeres, accumulation of DNA damage, disruption of the stem cell niche, and stem cell exhaustion [33,108,132]. The end result of these processes is an environment that promotes low-grade inflammation, along with decreased lymphoid progenitors and an accumulation of senescent lymphocytes with less diverse T cell repertoires [133][134][135][136]. Unlike lymphoid progenitors, myeloid progenitors are not diminished, which may contribute to increased incidence of anemias and myeloid dysplasias [137,138].…”

Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy

“…Authors would like to thank technical support received from Dr. Ponnuraj CP, Mrs. Gomathi, Mr. Kannan Muthuramalingam, and Mr. Sathya Murthi. This manuscript has been released as a Pre-Print at bioRxiv (73).…”

Alterations in Circulating Metabolites with Neuroinflammatory Property and Their Impact on Neurological Function in HIV-1–Infected Individuals on Long-Term Suppressive cART

“…Elevated systemic inflammation and machine learning predictions of inflammatory and neurological disease risks in HIV-1-infected persons from our previous studies also provide supportive evidence for the observed metabolic abnormalities associated with the central nervous system in HIV-1-infected individuals despite long-term suppressive ART. 3,4 To summarize, we identified alterations in levels of circulating metabolites that could increase the risk of FIG. 1.…”