Effectiveness of HIV prevention interventions targeting long-distance truck drivers: protocol for a systematic review and meta-analysis of global evidence

Introduction
Globally, long-distance truck drivers’ (LDTDs) risk of exposure to HIV infections is higher compared with other populations in transit. Thus, several HIV prevention interventions have been implemented, though to a narrower extent compared with other most at-risk populations. Consequently, the effectiveness of such interventions is not well understood. Therefore, a review is warranted to inform policymakers on the most effective HIV prevention interventions targeted for LDTDs.

Methods and analysis
The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines were followed. Original peer-reviewed interventional studies involving LDTDs of either gender aged above 18 years, and reporting findings on HIV prevention interventions from any part of the world will be included. Non-empirical research studies like systematic reviews, literature reviews and scoping reviews will be excluded. A comprehensive search will be done from PubMed, Cumulated Index to Nursing and Allied Health Literature and other five databases to identify eligible studies. The Rayyan online platform will be used for the screening of titles and abstracts. For the meta-analysis, a random-effects meta-analysis using the ‘metafor’ package in R software will be done. Where specific studies may not report adequate data for meta-analysis, their findings will be presented qualitatively. The Cochrane Collaboration tool and Joanna Brigs Checklist will be used to assess the quality and risk of bias in the included studies.

Ethics and dissemination
A formal ethical approval is not required for this systematic review and meta-analysis. The findings will be presented at scientific conferences and published in open-access peer-reviewed journals to reach policymakers, stakeholders and the scientific community.

PROSPERO registration number
CRD42024505542.

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Novembre 2024

Abstract 4120480: HIV-Nef extracellular vesicles utilize the novel Btk-NFκB-MerTK signaling axis to impair macrophage efferocytosis and promote atherosclerosis: A multiomics study

Circulation, Volume 150, Issue Suppl_1, Page A4120480-A4120480, November 12, 2024. Background:People living with HIV (PLWH) on anti-retroviral therapy remain at risk for cardiovascular diseases, including atherosclerosis. We hypothesized that persistent viral protein (HIV-Nef) in extracellular vesicles (EVs) modulate macrophage heterogeneity to impair atheroprotective efferocytosis to accelerate cardiovascular disease.Methods and Results:Macrophage heterogeneity was characterized in human primary macrophages (50,931 cells; 4 donors) stimulated with EVs engineered to contain HIV-Nef by simultaneous scRNAseq and scATACseq. Among 16 clusters (Fig.1A), two inflammatory Nef dominant clusters were characterized using gene set enrichment analysis. Gene regulatory network analysis of scRNAseq (pySCENIC) and transcription factor footprinting analysis of sc-ATACseq (ChromVar) suggest elevated NFκB activation in these clusters. Whole cell and sub-cellular compartmentalized proteomics of nucleus, cytosol, cell surface and secreted EVs indicate changes in immune response related biological pathways. Network analysis of our multi-omics data predicts Bruton Tyrosine Kinase (Btk) signaling as a potential contributor to Nef induced macrophage dysregulation. Pathway enrichment analysis of these multiomics dataset suggest Nef influences atheroprotective efferocytosis through the Btk-NFκB signaling axis. Spectral flow cytometry, high content imaging and multiplexed qPCR showed reduction in key effector of efferocytosis, MerTK. Btk inhibition using siRNA, reversible and irreversible Btk inhibitors restored MerTK expression and rescued efferocytosis. Importantly, CRISPRa based overexpression of MerTK in human primary macrophages rescued Nef impaired efferocytosis. Injection of HIV-Nef EVs into male and female C57BL6/J mice impaired efferocytosis of peritoneal and bone marrow derived macrophages which was rescued with Btk inhibitionin vivo. Critically, injection of HIV-Nef EV into male and female Ldlr-/-enhanced atherogenesis with larger aortic wall thickness and necrotic core (Fig.1B).Conclusion:Persistent Nef in EV in PLWH may modulate macrophage heterogeneity to impair efferocytosis. These findings may help develop novel atheroprotective therapies by restoring macrophage efferocytosis.

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Novembre 2024

Abstract 4145119: Implementation and Evaluation of a Life’s Essential 8 Risk Factor Screening Tool in a Public HIV Clinic in Tanzania

Circulation, Volume 150, Issue Suppl_1, Page A4145119-A4145119, November 12, 2024. Background:The burden of cardiovascular disease (CVD) is increasing among people with HIV (PWH) in sub-Saharan Africa. Integrating CVD screening into routine HIV care represents an opportunity to diagnose CVD at an earlier stage in a potentially high-risk population.Research questionsIs integrating CVD risk factor screening feasible and sustainable in a public HIV clinic in Mwanza, Tanzania? What is the magnitude of CVD risk of the general adult PWH population? What is the unmet need for blood pressure (BP) and diabetes management?Methods:We adapted the AHA Life’s Essential 8 (LE8) into a rapid questionnaire that was administered to every PWH in a large public adult HIV clinic. Questions included demographics; LE8 risk factors (BMI, diet, physical activity, sleep, and smoking); and the hypertension and diabetes continuum of care. Every patient had their BP measured; BP was measured two additional times for those with an initial BP >140/90 mmHg. We administered random blood glucose screening to anyone with a high BP, obese BMI, current smoking, or history of diabetes. Implementation and effectiveness were evaluated using the RE-AIM framework.Results:In 3 months, 1072 PWH were screened at least once. Mean age was 50 years and 72% were female. On average, PWH had a nutritious diet and received adequate physical activity per AHA guidelines. The prevalence of hypertension was 34%; the continuum of care is shown in Figure 1. Of those screened, 21% had diabetes or pre-diabetes. Evaluation via the RE-AIM framework is shown in Table 1. Successes included the reach and effectiveness of screening in only 3 months. Adoption was the biggest challenge due to staffing and supply constraints. The intervention was feasible, implemented with fidelity, and is ongoing.Conclusions:Integrating CVD risk screening into routine HIV care in a busy Tanzanian clinic was feasible and demonstrated a high magnitude of undiagnosed and untreated hypertension among the general PWH population.

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Novembre 2024

Abstract 4119611: Catheter ablation approach and outcome in HIV+ patients with atrial fibrillation: a systematic review and meta-analysis

Circulation, Volume 150, Issue Suppl_1, Page A4119611-A4119611, November 12, 2024. Background:Catheter ablation has emerged as an effective treatment option for atrial fibrillation (AF) in the general population. However, limited data exist on the outcomes of catheter ablation in patients infected with the Human Immunodeficiency Virus (HIV+) with concomitant AF.Objectives:This systematic review and single arm meta-analysis aims to comprehensively evaluate the literature on catheter ablation approach and outcome in HIV+ patients with AF.Methods:A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted following PRISMA guidelines.Studies meeting the intervention of catheter ablation for AF in HIV+ patients, using radiofrequency, cryoballoon, or pulsed field ablation techniques, were included and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software.Results:Three studies met the inclusion criteria, involving 89 HIV+ patients, with an average age of 51.5 years, of whom 83.1% were men, undergoing catheter ablation. Two studies performed received isolation of the pulmonary vein (PV) + posterior wall and superior vena cava. And one study evaluated only the isolation of the pulmonary veins. Of these patients, 43.8% had paroxysmal AF and 56.1% had persistent AF. In two studies reporting freedom from atrial arrhythmias, all patients (62) experienced recurrence of atrial arrhythmias within 5 years of follow-up. Freedom from repeat ablation was 6.26% (Figure 1A). The rate of Pulmonary Vein Trigger was 31.28% (Figure 1B), while the rate of Non-Pulmonary Vein Trigger (non-PV) was 76.64% (Figure 1C).Conclusion:In this systematic review and meta-analysis assessing outcomes of ablation in HIV patients with AF, we observed a similar prevalence of paroxysmal and persistent AF. Furthermore, contrary to the non-HIV+ patients, a high incidence of non-pulmonary vein triggers of AF was noted in this population.

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Novembre 2024

Abstract 4137891: Treated HIV infection is not associated with carotid vascular inflammation or plaque progression as assessed by dynamic contrast magnetic resonance imaging

Circulation, Volume 150, Issue Suppl_1, Page A4137891-A4137891, November 12, 2024. Background:Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with HIV (PLWH) despite effective viral suppression with antiretroviral therapy (ART).Question:We investigated differences in carotid vascular inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (n = 50; on stable ART with CD4 >250 cells/mm3, viral load 6 months) and HIV-uninfected controls (n = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease.Methods&Results:Participants were >40 years old at enrollment, 8% female, and had a high prevalence of cardiovascular risk factors (Table 1). Measures of carotid inflammation and capillary permeability (Ktrans), neovascularization (Vp), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging. Both PLWH and controls demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 mg/dL vs 12.8 mg/dL; p = 0.026). HIV was not associated with baseline, follow-up, or change in markers of systemic inflammation assessed by plasma cytokines (C-reactive protein, interleukin-6, interleukin-1ß), nor vascular inflammation or plaque as assessed byKtrans,Vp, carotid wall thickness, or percent wall volume (Tables 2&3).Conclusions:In contrast to other studies of chronically treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque.

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Novembre 2024

Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure

Circulation, Volume 150, Issue Suppl_1, Page A4113164-A4113164, November 12, 2024. Intro:Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease.Aims:We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness.Methods:In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status.Results:Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load

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Novembre 2024