Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV

Abstract

Background:People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk.Methods:We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression.Results:Of the 312 participants included [70% living with HIV, median (interquartile range; IQR) age 55 (51–60) years; 82% male; 91% white], 36, 130, and 146 were in the ‘gut/immune activation’, ‘neurovascular’, and ‘reference’ cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5–14.5) and 10.2% (5.5–16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK [5.8% (1.0–10.7) and 3.1% (0.3–5.8)] scores were higher, respectively, for those in the ‘gut/immune activation’ and ‘neurovascular’ clusters compared to those in the reference cluster.Conclusions:People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV.

Comparison of Integrase Strand Transfer Inhibitors (INSTIs) and Protease-Boosted Inhibitors (PIs) on the Reduction in Chronic Immune Activation in a Virally Suppressed, Mainly Male Population Living with HIV (PLWH)

“…Individuals under cART experience serious non-AIDS events (SNAEs), such as non-AIDS malignancies, cardiovascular events, renal and hepatic diseases, bone disorders, and neurocognitive impairment [6][7][8]. SNAEs are considered the main causes of morbidity and mortality among PLWH in the cART era [6][7][8].…”

“…Chronic aberrant inflammation and intestinal bacterial translocation contribute to atherosclerosis, tumor development, and liver fibrosis [7][8][9][10]. Elevated levels of biomarkers associated with chronic inflammation and bacterial translocation increase the risk of cardiovascular diseases and malignancies, sharing similar pathophysiological mechanisms with the general population but not identical ones [3,4,9,11].…”

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen

“…With the increase in life expectancy among PLWH, the number of people over 50 years of age increases [ 2 ] which leads to an increase in age-related comorbidities. [ 3 ]. A plethora of mechanisms contribute to the pathogenesis of non-HIV-related diseases in HIV patients [ 3 ], and inflammation plays a central role [ 4 ].…”

Distinct inflammatory profiles linked to cardiovascular disease risk in HIV infection: implications for the design of preventive and therapeutic interventions

“…The REPRIEVE study showed distinct differences in inflammatory and immune proteomic profiles in PWH with subclinical coronary artery disease characterized by coronary plaque vs. coronary artery calcium deposition [18]. Refinements to the tentatively defined clusters of Sukumaran et al [19] based on much larger numbers could prove valuable in discriminating among subpopulations who might best benefit from targeted interventions mitigating specific inflammatory profiles, as well as optimize their preventive care. They may also assist in defining the role of inflammation in other non-AIDS causes of morbidity and mortality in PWH, such as chronic kidney disease (CKD).…”

“…But which specific cellular-and cytokine-based biomarkers might help guide interventions remains uncertain [2,[16][17][18]. Sukumaran et al [19] sought to address this knowledge gap by assessing 31 inflammatory biomarkers in a crosssectional study of 312 participants, 70% of whom were PWH. Ten-year CVD risk predictions calculated by QRISK score were examined across three different proinflammatory profiles they constructed: 'gut/immune activation', 'neurovascular', and 'reference'.…”