Patterns of Immune Activation in HIV and Non HIV Subjects and Its Relation to Cardiovascular Disease Risk

Abstract

IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression while adjusting for classic CVD risk factors.ResultsIn total, 185 HIV-positive and 104 HIV negative participants, 63% females, median age 40.7 years (IQR 35.4 – 47.7) were included. HIV-positive individuals were older (+6 years, p <0.01) and had a higher CIMT (p <0.01). No clear patterns of inflammation were identified by use of PCA. Following ANCOVA, nine immune markers differed significantly between HIV-positive and HIV-negative participants, including PDL1. PDL1 was independently associated with CIMT, but upon stratification this effect remained for HIV-negative individuals only.ConclusionHIV positive patients on stable ART and HIV negative controls had similar immune activation patterns. CVD risk in HIV-positive participants was mediated by inflammation markers included in this study.

Targeted plasma proteomics reveals upregulation of distinct inflammatory pathways in people living with HIV

“…Previous studies identified only a limited number of inflammatory biomarkers in PLHIV. For example, nine inflammation markers were found to be differentially expressed in a study of 185 well-treated PLHIV and 104 HC of South African ancestry, with only three proteins (CCL25, PD-L1, and CXCL10) being in agreement with our findings (FDR<0.05, same direction) ( Vos et al., 2021 ). Furthermore, two studies by Babu et al.…”

“…Assessment of the profile of plasma inflammatory proteins allows the study of complex biological pathways that may lead to the identification of novel therapeutic targets and disease biomarkers. Previous studies that assessed plasma protein profiles were limited by small sample size and/or lack of a proper validation cohort ( Babu et al., 2019a , 2019b ; deFilippi et al., 2020 ; Lemma et al., 2020 ; Sperk et al., 2018 ; Vos et al., 2021 ). In addition, other studies included only patients with central obesity and insulin resistance using statins ( deFilippi et al., 2020 ) or children with HIV infection ( Lemma et al., 2020 ).…”

High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV

“…Two hundred seventy-six plasma proteins involved in inflammatory, cardiometabolic, oncology, and neurology processes were differentially expressed in PLHIV compared to HCs, suggesting a systemic dysregulation of circulating protein concentrations in PLHIV on long-term ART. Most of the identified differentially expressed proteins were upregulated (266/276; 96%) and a novel finding (236/276; 86%), with some being identified in previous proteomic studies (13)(14)(15)(16)(17)19,20,22) as depicted in the Supplemental Table 4.…”

“…In particular, technologies for proteomic profiling can facilitate the monitoring of numerous cellular processes through the detection of a wide range of proteins, including intracellular, secreted, and low-abundance proteins. Previous proteomic studies in PLHIV on ART were able to provide substantial insight into the pattern of inflammation in chronic HIV infection in relation to non-AIDS comorbidities (13)(14)(15)(16)(17)(18)(19)(20)(21). However, all previous studies focused on a limited number of proteins and a systematic study of proteins is still lacking.…”

Echocardiographic assessment of left cardiac structure and function in ART-naïve people living with HIV/AIDS

“…Risk factors for HIV-comorbid CVD include traditional CVD risk factors, ART-related metabolic disorders, and chronic immune activation and in ammation associated with HIV infection [33,34]. In the multivariate regression analysis, in addition to the traditional factors of increased age and increased BMI, decreased CD4 cell count was an independent risk factor for LVDD in ART-naïve PLWHA.…”