Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

Cardiovascular–kidney–metabolic syndrome (CKMS) represents the intricate interconnection of cardiovascular, kidney, and metabolic disorders, with systemic inflammation now recognized as a key driver of both pathogenesis and prognosis. This systematic review aimed to synthesize current evidence on the prognostic value of inflammatory biomarkers in individuals with CKMS. A systematic search of PubMed, Embase, CINAHL, Web of Science, and Scopus were conducted to identify studies published between 1 January 2024 and 30 June 2025, following the recognition of CKMS as a distinct syndrome in December 2023. Eligible studies included adults (aged ≥ 18 years) with CKMS, that assesses one or more inflammatory markers and reported prognostic outcomes such as mortality or disease progression. Data extracted included study characteristics, biomarker types, outcome measures, and key findings. In addition to longitudinal cohorts, we included a small number of cross-sectional studies and treated them as association (non-prognostic) evidence analyzed in a separate stream from prognostic cohorts. Risk of bias was evaluated using the Quality in Prognostic Studies (QUIPS) tool. Due to considerable variability in prognostic outcomes, follow-up durations, and inflammatory indices, a meta-analysis was not feasible. Instead, a narrative synthesis was undertaken to summarize the evidence, identify consistent associations, and emphasize the need for standardized approaches and biomarker validation in future CKMS research. Analysis was conducted in line with the SWiM guidelines. Thirteen studies (n = 13) comprising 282,016 participants (100,590 males; 97,295 females) were included from 1404 initial records. Five of the studies were cross-sectional, providing information on associations rather than prognostic outcomes. Most were large-scale cohort studies conducted in the USA and China. Frequently assessed biomarkers included systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (hs-CRP/HDL-C), dietary inflammatory index (DII), and triglyceride–glucose (TyG) index. Elevated levels of these biomarkers were consistently associated with higher risk of all-cause and cardiovascular mortality, CKMS progression, and adverse metabolic outcomes. This review highlights systemic inflammation as a critical and associated marker of CKMS prognosis. Inflammatory biomarkers may assist in hypothesis generation, but clinical utility remains to be established pending standardized adjustment and external validation. Because CKMS has only recently been operationalized, we limited inclusion to studies published from 1 January 2024 onward, enhancing definitional comparability but narrowing the evidence base and potentially emphasizing early-adopter regions (predominantly the U.S. and China). Accordingly, these findings should be interpreted as early signals that require replication in diverse settings and confirmation through longitudinal and interventional studies to inform integrative CKMS management strategies. Across observational studies, the certainty of evidence is low to moderate due to indirectness and imprecision; findings should be treated as associational signals pending external validation.

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH.

Despite administering combination antiretroviral therapy (cART), people living with the human immunodeficiency virus (PLWH) have been identified to be at an elevated risk of cardiovascular diseases (CVDs). Notably, inflammation and endothelial activation are likely factors associated with increased CVD risk in PLWH. Thus, the present study reviews evidence reporting on the potential link between increased markers of inflammatory, endothelial activation, and CVD risk in PLWH on cART. Web databases incorporating Cochrane libraries, PubMed, Web of Science, Google Scholar, and ScienceDirect were searched to identify suitable clinical research reports. The validity and reliability of the quality of the included evidence were appraised utilising the Downs and Black checklist. Fifteen clinical research reports were incorporated within the present study, involving PLWH on cART (n=7117). We classified these research reports based on short-term (≤12 months) and prolonged exposure (˃ 12 months) to cART of PLWH. Overwhelming results showed that short- and long-term exposure to cART are closely associated with elevated markers of inflammation that were consistent with the existence of endothelial activation in PLWH on cART. Prominent inflammatory markers, which were elevated included interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor alpha (TNF-α). While those indicating endothelial activation included soluble intercellular and vascular adhesion molecule-1 (sICAM-1 and sVCAM-1). The quality of included research reports was relatively high, while there was very limited information on the effect of the specific type of cART. The current study supports the hypothesis indicating a close association between elevated inflammatory markers and endothelial activation potentially contributing to CVDs in PLWH on cART. However, these effects may be associated with prolonged exposure to cART in conjunction to specific cART-drug regimen combinations. Nonetheless, the available evidence is still very limited, and more research is needed to confirm these findings.

Objectives: There is a growing need to understand the potential role of soluble platelet selectin (sP-selectin) in sustained endothelial activation through increased levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion-1 (sVCAM-1) in people living with HIV (PLWH) on highly active antiretroviral therapy (HAART). Methodology: This was a cross-sectional study involving PLWH on HAART (n = 55), in comparison to PLWH not on treatment (HAART-naïve) (n = 29), and (iii) HIV negative controls (n = 48) from the Mankweng area in the Limpopo province, South Africa. We quantified serum levels of sP-selectin, together with sICAM-1 and sVCAM-1. Most of the HAART-exposed group were on treatment for <5 years. We further performed frequency distribution and descriptive statistics for categorical variables. Results: Soluble P-selectin was positively correlated with sVCAM-1 (r = 0.469; p<0.001) in PLWH on HAART, even after adjusting for confounding factor such as age, BMI, and total cholesterol (r = 0.467; p<0.001). Moreover, in PLWH on HAART sP-selecting was independently associated with the release of sVCAM-1 (β = 0.445; p<0.001), even after adjusting for confounders (β = 0.475; p = 0.001). Serum levels of low-density lipoprotein cholesterol (LDL-C) (p = 0.004) and total cholesterol (p<0.001) were significantly higher in PLWH on HAART as compared to the HAART-naïve group. Conclusion: There is a need for more studies to investigate the role of sP-selectin in promoting endothelial activation and CVD-risk in PLWH on HAART, especially within the sub-Saharan Africa region.