Associations Between Plasma Immunomodulatory and Inflammatory Mediators With VACS Index Scores Among Older HIV-Infected Adults on Antiretroviral Therapy

Abstract

The prevalence of age-related comorbidities is increased in people living with HIV, even in those well-controlled on combination antiretroviral therapy (ART). Persistent immune activation and inflammation may play pivotal roles in the pathogenesis; however, the burden of morbidities in the older HIV infected population may be exacerbated and driven by distinct mechanisms. In a cross sectional study of 45 HIV-infected participants 60 years or older, we examined the relationships between 14 immunomodulatory and inflammatory factors and the Veterans Aging Cohort Study (VACS) Index, a metric of multimorbidity and mortality comprised of age, CD4 count, hemoglobin, Fibrosis-4 [FIB-4], and estimated glomerular filtration rate [eGFR], by linear regression analysis. All participants were virally suppressed (<50 HIV RNA copies/mL), on ART, and primarily Caucasian (86.7%), and male (91.1%). Plasma levels of monocyte/macrophage-associated (neopterin, IP-10, sCD163, sCD14, and MCP-1) and glycan-binding immunomodulatory factors (galectin (Gal)-1, Gal-3, and Gal-9) were assessed, as well as inflammatory biomarkers previously linked to the VACS Index (i.e., CRP, cystatin C, TNF-α, TNFRI, IL-6, and D-dimer) for comparison. In regression analysis, higher VACS index scores were associated with higher levels of neopterin, cystatin C, TNFRI, and Gal-9 (all p < 0.05), potentially driven by correlations found with individual VACS components, including age, CD4 count, FIB-4, and eGFR. Gal-9, cystatin C, and TNFRI directly correlated with the extent of multimorbidity. Multiple correlations among markers were observed, suggesting an interplay of overlapping, but distinct, pathways. Collectively, in addition to cystatin C and TNFRI, both galectin-9 and neopterin, independently emerged as novel fluid markers of the VACS Index and Premeaux et al. Immunomodulatory Factors and HIV Comorbidities burden of comorbidity and may further guide in understanding pathogenic mechanisms of age-related disorders in older HIV-infected individuals on suppressive ART.

High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia

“…To assess their exact roles, the application of the strategy used in the VA COVID-19 (VACO) should be developed using nationwide medical administrative data [ 67 ]. In HIV study, higher Veterans Aging Cohort Study index scores were associated with higher levels of neopterin, cystatin C, tumor necrosis factor receptor 1 and Gal-9 in individuals under therapy [ 68 ].…”

No Evidence that Ongoing HIV-Specific Immune Responses Contribute to Persistent Inflammation and Immune Activation in Persons on Long-Term ART

“…This is the first study to our knowledge assessing the relationships between HIV-specific immune responses with clinically relevant inflammation and immune activation indicesincluding plasma IL-6 (associated with risk for non-AIDS-defining cancers, cardiovascular disease, renal disease, frailty, and all-cause mortality [27][28][29][30][31][32][33]), hsCRP (cardiovascular disease, incident diabetes, mortality [27,29,34,35]), IP-10 (associated with a metric of multimorbidity and mortality [36]), sCD14 (chronic obstructive pulmonary disease, neurocognitive impairment, frailty, mortality [33,[37][38][39][40]), sCD163 (neurocognitive impairment [41]), and TNF-α (renal disease, frailty [31,33]) -in a cohort of chronic progressors on long-term ART. Our findings indicate that neither HIV-specific T-cell responses, assessed by ex vivo IFN-γ production, nor HIV antibody levels influence on-ART levels of inflammation and immune activation.…”

Factors associated to neurocognitive impairment in older adults living with HIV

“…Frailty was valuated with the Clinical Frailty scale and comorbidity was assessed using the Charlson Comorbidity index, which was also categorized in no comorbidities, medium–low (1–2 comorbidities) or high (≥ 3 comorbidities). All included individuals had a VACS index at baseline [ 15 ].…”

“…NI plays a preponderant role in the deterioration of the quality of life and functionality, carrying an accelerated appearance of frailty [ 10 – 12 ]. Many mechanisms for NI such as CNS virus persistence despite suppressed peripheral viral load, continuous activation of monocytes in the CNS [ 13 – 15 ], HIV-specific persistent inflammatory response or potential ART CNS toxicities [ 5 , 16 ] have been proposed. All of these seem to be keystone in the pathophysiology of neurocognitive deterioration.…”