HIV-associated Cardiovascular Disease Research Articles

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

HIV infection and cardiovascular disease have both shared and distinct monocyte gene expression features: Women's Interagency HIV study.

Persistent inflammation contributes to the development of cardiovascular disease (CVD) as an HIV-associated comorbidity. Innate immune cells such as monocytes are major drivers of inflammation in men and women with HIV. The study objectives are to examine the contribution of circulating non-classical monocytes (NCM, CD14dimCD16+) and intermediate monocytes (IM, CD14+CD16+) to the host response to long-term HIV infection and HIV-associated CVD. Women with and without chronic HIV infection (H) were studied. Subclinical CVD (C) was detected as plaques imaged by B-mode carotid artery ultrasound. The study included H-C-, H+C-, H-C+, and H+C+ participants (23 of each, matched on race/ethnicity, age and smoking status), selected from among enrollees in the Women's Interagency HIV Study. We assessed transcriptomic features associated with HIV or CVD alone or comorbid HIV/CVD comparing to healthy (H-C-) participants in IM and NCM isolated from peripheral blood mononuclear cells. IM gene expression was little affected by HIV alone or CVD alone. In IM, coexisting HIV and CVD produced a measurable gene transcription signature, which was abolished by lipid-lowering treatment. In NCM, versus non-HIV controls, women with HIV had altered gene expression, irrespective of whether or not they had comorbid CVD. The largest set of differentially expressed genes was found in NCM among women with both HIV and CVD. Genes upregulated in association with HIV included several potential targets of drug therapies, including LAG3 (CD223). In conclusion, circulating monocytes from patients with well controlled HIV infection demonstrate an extensive gene expression signature which may be consistent with the ability of these cells to serve as potential viral reservoirs. Gene transcriptional changes in HIV patients were further magnified in the presence of subclinical CVD.

Coronary heart disease in patients with human immunodeficiency virus infection

According to the World Health Organization, more than 38 million people are carriers of the human immunodeficiency virus (HIV). The relative risk of cardiovascular events in patients with HIV infection is 1.52 times higher than those without it. An HIV-positive status is associated with a 50% increased risk of acute myocardial infarction. The mechanisms of CVD development caused by HIV activity are not fully understood, and the contribution of traditional risk factors cannot fully explain such a high potential for coronary heart disease (CHD) in patients with HIV infection. Data suggest that HIV-associated chronic inflammation and immune system activation may lead to progressive endothelial dysfunction and vascular damage. The pathogenesis of atherosclerosis and, consequently, CHD in HIV infection is extremely versatile and poorly studied. The key mechanisms in HIV-associated CHD include the effect of HIV proteins on immunocompetent cells and vascular endothelium, immunodeficiency, translocation of microorganisms from the gut, and chronic inflammation with platelet activation. Despite considerable progress in understanding HIV-associated cardiovascular disease, many unresolved questions remain. Even with effective viral suppression, inflammation and immune dysregulation appear to increase the risk of cardiovascular complications. The lack of large-scale clinical studies on the prevention and treatment of cardiovascular disease in HIV is very important. Nevertheless, some important features should be considered in the management of patients with HIV infection.

Association of HIV Infection With Cardiovascular Pathology Based on Advanced Cardiovascular Imaging

HIV-associated cardiovascular disease is increasing in prevalence, but its mechanisms remain poorly understood. To systematically review data from advanced cardiovascular imaging studies evaluating computed tomographic coronary angiography, positron emission tomography (PET), and cardiac magnetic resonance (MR), in people living with HIV compared with uninfected individuals. Three databases and Google Scholar were searched for studies assessing cardiovascular pathology using computed tomographic coronary angiography, cardiac MR, PET, and HIV from inception to February 11, 2022. Two reviewers selected original studies without any restrictions on design, date, or language, investigating HIV and cardiovascular pathology. One investigator extracted data checked by a second investigator. Prevalence ratios (PRs) and differences in inflammation among people living with HIV and uninfected individuals were qualitatively synthesized in terms of cardiovascular pathology. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tool for observational studies. Primary outcomes were computed tomographic coronary angiography-defined moderate to severe (≥50%) coronary stenosis, cardiac MR-defined myocardial fibrosis identified by late gadolinium enhancement, and PET-defined vascular and myocardial target to background ratio. Prevalence of moderate to severe coronary disease, as well as myocardial fibrosis, and PRs compared with uninfected individuals were reported alongside difference in vascular target to background ratio. Forty-five studies including 5218 people living with HIV (mean age, 48.5 years) and 2414 uninfected individuals (mean age, 49.1 years) were identified. Sixteen studies (n = 5107 participants) evaluated computed tomographic coronary angiography; 16 (n = 1698), cardiac MRs; 10 (n = 681), vascular PET scans; and 3 (n = 146), both computed tomographic coronary angiography and vascular PET scans. No studies originated from low-income countries. Regarding risk of bias, 22% were classified as low; 47% moderate; and 31% high. Prevalence of moderate to severe coronary disease among those with vs without HIV ranged from 0% to 52% and 0% to 27%, respectively, with PRs ranging from 0.33 (95% CI, 0.01-15.90) to 5.19 (95% CI, 1.26-21.42). Prevalence of myocardial fibrosis among those with vs without HIV ranged from 5% to 84% and 0% to 68%, respectively, with PRs ranging from 1.01 (95% CI, 0.85-1.21) to 17.35 (95% CI, 1.10-274.28). Differences in vascular target to background ratio among those with vs without HIV ranged from 0.06 (95% CI, 0.01-0.11) to 0.37 (95% CI, 0.02-0.72). In this systematic review of studies of advanced cardiovascular imaging, the estimates of the associations between HIV and cardiovascular pathologies demonstrated large amounts of heterogeneity. The findings provide a summary of the available data but may not be representative of all individuals living with HIV, including those from low-income countries with higher HIV endemicity.

Prevention of heart failure, tachyarrhythmias and sudden cardiac death in HIV.

To summarize the state-of-the-art literature on the epidemiology, disease progression, and mediators of heart failure, tachyarrhythmias, and sudden cardiac death in people living with HIV (PLWH) to inform prevention strategies. Recent studies corroborate the role of HIV as a risk enhancer for heart failure and arrhythmias, which persists despite adjustment for cardiovascular risk factors and unhealthy behaviors. Immune activation and inflammation contribute to the risk. Heart failure occurs more frequently at younger ages, and among women and ethnic minorities living with HIV, highlighting disparities. Prospective outcome studies remain sparse in PLWH limiting prevention approaches. However, subclinical cardiac and electrophysiologic remodeling and dysfunction detected by noninvasive testing are powerful disease surrogates that inform our mechanistic understanding of HIV-associated cardiovascular disease and offer opportunities for early diagnosis. Aggressive control of HIV viremia and cardiac risk factors and abstinence from unhealthy behaviors remain treatment pillars to prevent heart failure and arrhythmic complications. The excess risk among PLWH warrants heightened vigilance for heart failure and arrhythmic symptomatology and earlier testing as subclinical abnormalities are common. Future research needs include identifying novel therapeutic targets to prevent heart failure and arrhythmias and testing of interventions in diverse groups of PLWH.

Preventing cardiovascular disease in midlife women with HIV: An examination of facilitators and barriers to heart health behaviors

Midlife women with HIV (WWH) are disproportionately impacted by cardiovascular disease (CVD), yet little is known about perceptions of CVD risk and the factors that influence engagement in heart health behaviors in this population. Few (if any) studies have used a qualitative approach to examine these perceptions, which has important implications for minimizing the negative impact of HIV-related noncommunicable diseases, the risk for which increases after midlife. Eighteen midlife WWH (aged 40–59) in Boston, MA, completed semistructured interviews to explore perceptions of CVD, HIV, and barriers and facilitators to healthy lifestyle behaviors. Interviews were analyzed via thematic analysis. Participants viewed heart health as important but were unaware of HIV-associated CVD risk. Facilitators included family and generational influences, social support, and access to resources. Physical symptoms, menopause, mental health challenges, and limited financial resources were barriers. Midlife WWH may benefit from tailored CVD prevention interventions that target their unique motivations and barriers to healthy behaviors.

Prevalence of cardiovascular diseases in HIV positive patients: A comparative study between seropositive and seronegative patients living in Libreville, Gabon

The profile of HIV-associated cardiovascular disease has changed with the high coverage of antiretroviral treatment (ART). Data are lacking in Gabon. To compare the type and the frequency of cardiovascular manifestations in hospitalized HIV-infected patients (PLHIV) and seronegative ones. This was a retrospective analytical study performed by analyzing the files of patients hospitalized for a cardiovascular diseases and who benefited from an HIV serology in the cardiology department of the centre hospitalier universitaire de Libreville from January 2015 to December 2018. The files of 82 PLHIV and 150 HIV negative were analyzed. The mean CD4 count in PLHIV was 189 ± 170/mm 3 and 45.1% were on ART. PLHIV were more frequently less than 50 years old (70.6% vs. 43.3% of HIV negative; P < 0.01) and they were more frequently female (67.1% vs. 36.0% of HIV negative; P < 0.01). Pericarditis (25.6% vs. 11.3% in seronegatives; P = 0.01) mainly due to tuberculous (85.2%), myocarditis (14.6% vs. 4.0% in seronegatives; P = 0.03) and repolarization disorders (32.9% vs. 15.3% in HIV negative; P < 0.01) predominated in PLHIV. Atheromatous vascular diseases were more frequent in HIV negative patients (23.1%) compared to seropositive (6.1%) ( P < 0.01). The death of PLHIV was mainly due to pericarditis (71.4%) while HIV negative patients died more frequently for heart failure (46.7%). The cardiovascular manifestations linked to HIV immunosuppression are still frequent in Libreville.

Clonal Hematopoiesis Is Associated with Risk of Cardiovascular Disease in Individuals with Human Immunodeficiency Virus

IntroductionAn estimated 1.2 million individuals in the United States are living with HIV (www.hiv.gov). Thanks to modern antiretroviral therapies (ART), the life expectancies of individuals living with HIV now approach those of people without HIV (Marcus 2020). But with this, an increase in the proportion of deaths due to non-infectious causes has occurred including, predominately, cardiovascular disease (CVD). Multiple studies have shown that HIV infection is an independent risk factor for cardiovascular disease. This increased risk is multifactorial due to an increased prevalence of traditional CVD risk factors and HIV-specific risk factors including ART, chronic inflammation and immune activation (Hsue 2010). Clonal Hematopoiesis, characterized by the expansion of blood cells stemming from a mutant hematopoietic stem/progenitor cell (HSPCs) is an emerging risk factor for cardiovascular disease. Mechanistically, this is thought to be driven, at least in part, by CH-induced proinflammatory circulating leukocytes (Jaiswal 2017, Bick 2020). Recent data suggest that inflammatory states may also promote the expansion of DNMT3A and TET2 CH mutant HSPCs suggesting a potential feedback loop (Zheng 2019, King 2019). CH has been recently reported to be increased among individuals living with HIV (Dharan 2021). Whether CH is a risk factor for HIV-associated CVD is not known. Given evidence of an increased prevalence of CH among those with HIV, we hypothesized that CH would predict risk of CVD.MethodsWe performed a nested case-control study drawn from the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) observational study which was a long-term study of individuals with newly diagnosed HIV receiving ART (N=4,371). Cases who developed a cardiovascular event were matched to controls with no event based on age at blood draw and sex. Peripheral blood mononuclear cells (PMBCs) were isolated from the blood draw closest to the time of CVD event or time of censoring, for cases and controls respectively. Extracted DNA was subjected to whole exome sequencing (WES) at a median depth of 500x. We also included WES data from 267 children sequenced using the same platform as a technical panel of normal (PON). Mutation calling was performed using Mutect2, VarDict and Varscan2. We retained variants that met the following criteria: 1) passed by at least two callers 2) showed statistically significant higher variant allele fraction (VAF) compared to our PON 3) had VAF between 2-35% 4) at least 6 reads supporting the variant 5) passed additional post-calling filters for germline variants and sequencing artifacts 6) were annotated as a putative driver of CH based on previously defined criteria.ResultsOver 13 years of follow-up we observed 83 cardiovascular events: 4 cases of ASC, 14 of stroke, 25 of cerebrovascular accident, 37 of myocardial infarction, 2 of peripheral artery disease, and 1 heart failure. The mean age of our participants was 51.6 years, 81% were male, 35% percent were African-American, 17% were Hispanic and 2% were Asian. Among 161 participants (83 cases and 78 controls) we observed at least one CH mutation in 14% of participants (18% of cases and 10% of controls). The median VAF was 3.5% with 23 individuals harboring a median of 1 mutation (range 1-2). In a conditional logistic regression model adjusted for race, Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score and stratified by case-control matched pairs, CH was significantly associated with CVD (OR=3.70, 95% CI 1.03-13.23 p=0.045). Because of the possible confounding effects of classes of ART therapy on the CH-CVD association, we explored whether the prevalence of CH differed based on prior exposure to ART sub-class(es). We did not observe differences in the frequency of CH among individuals with prior exposure to different ART regimens (Non-Nucleoside Reverse Transcriptase Inhibitors 14%, Nucleoside reverse transcriptase inhibitors 17%, Protease inhibitors 20%, Integrase inhibitors 18%)ConclusionsAmong individuals with HIV, CH is associated with a nearly four-fold increased risk of CVD. These findings highlight the relevance of CH to HIV-associated CVD and provide support for interventions targeting potential CH-induced pro-inflammatory states among patients with HIV. DisclosuresErlandson: Gilead Sciences: Consultancy, Research Funding; Viiv Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy. Bolton: bristol myers squibb: Research Funding.

Alteration of type I interferon response is associated with subclinical atherosclerosis in virologically suppressed HIV-1-infected male patients.

Given human immunodeficiency virus‐1 (HIV‐1)‐infected patients have alterations in the type I interferon (IFN‐I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN‐I response and subclinical cardiovascular disease (CVD) association in HIV‐1‐infected patients. Transcript levels of IFN‐α/β and IFN‐stimulated gene 56 (ISG56) were evaluated by RT/real‐time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV‐1‐positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima‐media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti‐HIV drugs (D:A:D) were also measured. Increased IFN‐α, IFN‐β, and ISG56 levels were observed in all HIV‐1‐infected males compared to healthy controls (p < .001 for all genes analyzed). HIV‐1‐infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p = .019), which was correlated with IFN‐β and ISG56 levels. HIV‐1‐infected males with enhanced IFN‐I levels and stenosis displayed a higher ASCVD calculated risk (p = .011) and D:A:D score (p = .004). Also, there was a trend toward higher IFN‐α and ISG56 mRNA levels in HIV‐1‐positive patients with an increased cIMT (p > .05). Dysregulation of IFN‐I response might participate in the pathogenesis of HIV‐1‐associated CVD.

Vitamin D insufficiency is associated with subclinical atherosclerosis in HIV-1-infected patients on combination antiretroviral therapy

Objectives: Vitamin D insufficiency has been associated with faster progression of atherosclerosis and increased cardiovascular disease risk, but limited data are available in HIV-infected people. So, we examined potential correlation between vitamin D status and atherosclerosis in people living with HIV.Methods: A cross-sectional study was performed including adult HIV-infected patients on stable antiretroviral therapy, aged 40–60 years, and with a recent carotid ultrasonography. Subclinical atherosclerosis was defined as a carotid intima-media thickness (IMT) ≥0.9 mm at any site. Patients with diabetes mellitus or atherosclerotic cardiovascular disease were excluded.Results: On the whole, 188 patients were enrolled: 86.2% were men and the mean age was 49.1 years. The mean CD4 T lymphocyte count was 567 cells/mm3, 176 (93.6%) had plasma HIV RNA <20 copies/mL, 51.1% were smoker, 29.2% had hypertension, 27.7% metabolic syndrome, and 44.7% LDL cholesterol >150 mg/dL. The mean serum concentration of vitamin D was 35.2 ng/mL, and 84 (44.6%) patients had a vitamin D insufficiency (<30 ng/mL). Subclinical atherosclerosis was reported in 105 (55.8%) and the mean vitamin D concentration was significantly lower among patients with subclinical atherosclerosis than among those without (18.2 vs 41.3 ng/mL, p < 0.001). Moreover, the multivariate linear regression analysis adjusted by confounding factors showed an independent association between subclinical atherosclerosis and vitamin D insufficiency, age >50 years, smoking, hypertension, metabolic syndrome, higher BMI, higher LDL cholesterol, longer duration of HIV infection, lower nadir CD4 cell count, and longer exposure to boosted protease inhibitors.Conclusion: In our study, vitamin D insufficiency is significantly associated with subclinical atherosclerosis, so its role in HIV-associated cardiovascular disease should be further evaluated as a possible target for intervention.

Elevated Lipoprotein(a) in Perinatally HIV-Infected Children Compared With Healthy Ethnicity-Matched Controls.

BackgroundHIV-associated cardiovascular disease (CVD) risk in combination antiretroviral therapy (cART)–treated perinatally HIV-infected patients (PHIV+) remains unknown due to the young age of this population. Lipoprotein(a) (Lp(a)) has been established as an independent causal risk factor for CVD in the general population but has not been well established in the population of PHIV+.MethodsWe cross-sectionally compared lipid profiles, including nonfasting Lp(a), together with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides between 35 cART-treated PHIV+ children aged 8–18 years and 37 controls who were matched for age, sex, ethnicity, and socioeconomic status. We explored associations between Lp(a) and disease- and treatment-related factors (inflammation, monocyte activation, and vascular), biomarkers, and neuroimaging outcomes using linear regression models.ResultsPHIV+ children had significantly higher levels of Lp(a) compared with controls (median, 43.6 [21.6–82.4] vs 21.8 [16.8–46.6] mg/dL; P = .033). Other lipid levels were comparable between groups. Additional assessment of apolipoprotein B, apolipoprotein CIII, apolipoprotein E, and APOE genotype revealed no significant differences. Higher Lp(a) levels were associated with higher plasma apoB levels and with lower monocyte chemoattractant protein-1 and TG levels in PHIV+ children. Lp(a) was not associated with HIV- or cART-related variables or with neuroimaging outcomes.ConclusionscART-treated PHIV+ children appear to have higher levels of Lp(a) compared with ethnicity-matched controls, which may implicate higher CVD risk in this population. Future research should focus on the association between Lp(a) and (sub)clinical CVD measurements in cART-treated PHIV+ patients.Dutch Trial Register numberNRT4074.

Elevated indoleamine-2,3-dioxygenase enzyme activity in a novel mouse model of HIV-associated atherosclerosis.

HIV atherosclerosis and cardiovascular disease (CVD) represent a significant human health burden in the era of combination antiretroviral therapy (cART). The pathogenesis of HIV atherosclerosis is still poorly understood, due, in part, to the lack of a suitable small animal model. Indoleamine-2,3-dioxygenase (IDO) enzyme activity is the first and rate-limiting step in tryptophan catabolism and is measured by the kynurenine to tryptophan ratio (KTR). The serum KTR is a biomarker of inflammation and has recently been implicated as an important risk factor for CVD in patients living with HIV (PLWH) who are virologically suppressed under cART. However, IDO activity in HIV-associated CVD has not been studied in mouse model before. A novel mouse model of HIV atherosclerosis (Tg26/ApoE) was generated and examined for IDO activity and atherogenesis throughout 8 weeks on a high-fat diet. Tg26/ApoE mice were compared with Tg26 and ApoE single transgenic mice, before and during a high-fat diet. Serum kynurenine, tryptophan and percentage of aortic plaque formation were measured. Additionally, levels of relevant cytokines were investigated in Tg26/ApoE and ApoE. Tg26/ApoE developed an accelerated atherosclerosis with increasing levels of KTR that were associated with plaque progression. This accelerated plaque was potentially driven by elevated levels of circulating IL-6. These results indicate that Tg26/ApoE serve as a new mouse model for HIV-induced atherogenesis, and aid in understanding the role of tryptophan catabolism in the pathogenesis of HIV atherosclerosis/CVD.

HIV-associated cardiovascular disease is global scourge.

HIV-associated cardiovascular disease is global scourge.

HIV-associated cardiovascular disease is global scourge

HIV-associated cardiovascular disease is global scourge

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV. We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV. In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho. People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions. URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

Cardiovascular disease burden among human immunodeficiency virus-infected individuals

Human Immunodeficiency Virus (HIV) infection affects 36.7 million people worldwide, it accounted for 1.1 million deaths in 2015. The advent of combined antiretroviral therapy (cART) has been associated with a decrease in HIV-related morbidity and mortality. However, there are increasing concerns about long-lasting effects of chronic inflammation and immune activation, leading to premature aging and HIV-related mortality. Cardiovascular diseases, especially coronary artery disease, are among the leading causes of death in HIV-infected patients, accounting for up to 15% of total deaths in high income countries. Furthermore, as cART availability expands to low-income countries, the burden of cardiovascular related mortality is likely to rise. Hence, over the next decade HIV-associated cardiovascular disease burden is expected to increase globally. In this review, we summarize our understanding of the pathogenesis and risk factors associated with HIV infection and cardiovascular disease, in particular coronary artery disease.

Epicardial adipose tissue volume and cardiovascular risk indices among asymptomatic women with and without HIV.

Mechanisms underlying the heightened myocardial infarction risk among HIV-infected women (versus non-HIV-infected women) remain unclear. Our objectives were to assess epicardial adipose tissue (EAT) volume and its associations among asymptomatic women with and without HIV. A total of 55 HIV-infected and 27 non-HIV-infected women without known cardiovascular disease who underwent cardiac CT and metabolic/immune phenotyping were included. EAT volume derived from CT was compared among women with and without HIV, and within-group EAT associations were assessed. Next, immune and atherosclerotic plaque parameters were compared among groups stratified by HIV serostatus and high/low EAT (defined in reference to median EAT for each serostatus group). Asymptomatic HIV-infected women and age-matched non-HIV-infected women with comparable mean body mass index (28 ±1 versus 29 ±1 kg/m2) had similar median (IQR) volumes of EAT (54 [41-79] versus 65 [41-78] cm3; P>0.05); however, different within-group associations were noted. Markers of monocyte activation/arterial inflammation differed by HIV serostatus/EAT volume subgroup (CXCL10 [P=0.02], sCD163 [P=0.004], sCD14 [P=0.03], Lp-PLA2 [P=0.04]; P for overall ANOVA) and were highest among HIV-infected women with excess EAT (versus HIV-infected women without excess EAT, non-HIV-infected women with excess EAT and non-HIV-infected women without excess EAT). The percentage of segments with non-calcified coronary plaque also differed by HIV serostatus/EAT volume subgroup and was highest among HIV-infected women with excess EAT. Asymptomatic women with and without HIV have similar volumes of EAT, but drivers of EAT may differ between groups. HIV-infected women with excess EAT have highest-level immune activation and the highest percentage of non-calcified plaque. Future studies are needed to determine whether EAT contributes pathogenetically to HIV-associated cardiovascular disease in women.

Reducing medical comorbidities associated with long-term HIV infection: beyond optimizing antiretroviral therapy regimens.

Reducing medical comorbidities associated with long-term HIV infection: beyond optimizing antiretroviral therapy regimens.

Review of cardiovascular magnetic resonance in human immunodeficiency virus-associated cardiovascular disease.

Despite ongoing advances in the treatment of patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), they remain a major global public health concern conferring an increased risk of morbidity and mortality in affected individuals. This is, in part, because of the widespread dysfunction imposed by HIV and its treatment on the cardiovascular system, including the myocardium, valvular apparatus, pericardium and coronary, pulmonary and peripheral vasculature. In recent times, cardiovascular magnetic resonance (CMR) imaging has emerged as the gold standard tool for assessment of a variety of indications, allowing comprehensive characterisation of functional, morphological, metabolic and haemodynamic sequelae of several cardiovascular pathologies. Furthermore, continued advancement in imaging techniques has yielded novel insights into the underlying pathophysiology and guides future therapeutic strategies. In this article, we review the various clinical phenotypes of HIV-associated cardiovascular disease and highlight the utility of CMR in their assessment.