Changes in Atherosclerotic Cardiovascular Disease Risk Scores in a Predominantly Black Cohort with HIV and Associated Comorbidities: A Preliminary Study.

INTRODUCTION: People with HIV (PWH) have an increased risk of atherosclerotic cardiovascular disease (ASCVD) compared to non-PWH, but the reasons for this increased risk remain elusive. We investigated the change in ASCVD risk scores over 4 years to identify clinical factors associated with change in risk scores or high-risk scores. METHODS: We conducted a preliminary study using retrospective analysis of PWH, between 40 and 75 years old, seen at the Evelyn Jordan Center with at least two routine HIV visits. We collected clinical and demographic data and calculated the ASCVD risk scores using the Pooled Cohort Equation. Exploratory analyses examined change in risk score categories over time. Final adjusted analysis examined factors associated with change in continuous risk scores over time. RESULTS: Our sample included 187 PWH; 166 were black/African American and 79 were female. We found no significant change in ASCVD risk score over time. The risk score was significantly higher in PWH with hepatitis C (7.34%; 95% CI: 2.59, 12.09; p = 0.003) and trended higher in those with dual hepatitis B/C and hepatitis B compared to those without hepatitis (p = 0.07). CONCLUSION: We found that ASCVD risk did not change over a 4-year period among predominantly black young PWH, but infection with hepatitis C and dual hepatitis B/C were associated with higher ASCVD risk scores. Our findings illustrate the need for further longitudinal studies evaluating change in cardiovascular disease (CVD) risk and investigating viral hepatitis as an added potential contributor to increased CVD risk in high-risk, vulnerable populations.

Inflammatory and Immune Mechanisms for Atherosclerotic Cardiovascular Disease in HIV.

Atherosclerotic vascular disease disproportionately affects persons living with HIV (PLWH) compared to those without. The reasons for the excess risk include dysregulated immune response and inflammation related to HIV infection itself, comorbid conditions, and co-infections. Here, we review an updated understanding of immune and inflammatory pathways underlying atherosclerosis in PLWH, including effects of viral products, soluble mediators and chemokines, innate and adaptive immune cells, and important co-infections. We also present potential therapeutic targets which may reduce cardiovascular risk in PLWH.

Coronary artery endothelial function and aging in people with HIV and HIV-negative individuals.

Coronary artery disease (CAD) is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH) and impaired coronary endothelial function (CEF) plays a central role in the pathogenesis of CAD. Age-related impaired CEF among PWH, however, is not well characterized. We investigated the association between CEF and age in males and females with and without HIV using 3-T magnetic resonance imaging (MRI). We measured the changes in coronary cross-sectional area (CSA) and coronary blood flow during isometric handgrip exercise (IHE), an established endothelial-dependent stressor with smaller increases in CSA and coronary blood flow indicative of impaired CEF. We included 106 PWH and 82 individuals without HIV. Differences in demographic and clinical characteristics between PWH and individuals without HIV were explored using Pearson's χ2 test for categorical variables and Welch's t test for continuous variables. Linear regression models were used to examine the association between CEF and age. CEF was significantly lower in PWH as compared with individuals without HIV. Coronary endothelial dysfunction was also present at younger ages in PWH than in the individuals without HIV and there were significant differences in CEF between the PWH and individuals without HIV across age groups. Among the individuals without HIV, the percent changes in CSA were inversely related to age in unadjusted and adjusted models. There was no significant association between CEF and age in PWH. To the best of our knowledge, this is the first study to examine the relationship between age and CEF in PWH, and our results suggest that factors other than age significantly impair CEF in PWH across the life span.NEW & NOTEWORTHY This is the first study to examine the relationship between age and coronary endothelial function (CEF) in people with human immunodeficiency virus (HIV) (PWH). CEF was assessed using magnetic resonance imaging (MRI) in people with and without HIV. Although age and CEF were significantly inversely related in individuals without HIV, there was no association between age and CEF in PWH.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.

Persistent gamma delta T-cell dysfunction in chronic HCV infection despite direct-acting antiviral therapy induced cure.

Immune dysfunction is a hallmark of chronic HCV infection and viral clearance with direct antivirals recover some of these immune defects. TCRVγ9Vδ2 T-cell dysfunction in treated HCV patients however is not well studied and was the subject of this investigation. Peripheral blood cells from patients who had achieved sustained virologic response (SVR) or those who had relapsed after interferon-free therapy were phenotyped using flow cytometry. Functional potential of Vγ9Vδ2 T cells was tested by measuring proliferation in response to aminobisphosphonate zoledronic acid, and cytotoxicity against HepG2 hepatoma cell line. TCR sequencing was performed to analyse impact of HCV infection on Vδ2 T-cell repertoire. Vγ9Vδ2 cells from patients were activated and therapy resulted in reduction of CD38 expression on these cells in SVR group. Relapsed patients had Vδ2 cells with persistently activated and terminally differentiated cytotoxic phenotype (CD38+ CD45RA+ CD27- CD107a+ ). Irrespective of outcome with therapy, majority of patients had persistently poor Vδ2 T-cell proliferative response to zoledronate along with lower expression of CD56, which identifies anti-tumour cytotoxic subset, relative to healthy controls. There was no association between the number of antigen reactive Vγ2-Jγ1.2 TCR rearrangements at baseline and levels of proliferation indicating nonresponse to zoledronate is not due to depletion of phosphoantigen responding chains. Thus, HCV infection results in circulating Vγ9Vδ2 T cells with a phenotype equipped for immediate effector function but poor cytokine response and expansion in response to antigen, a functional defect that may have implications for susceptibility for carcinogenesis despite HCV cure.

Association of Lipoprotein(a) with peri-coronary inflammation in persons with and without HIV infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) (PWH) have an increased risk of developing cardiovascular disease (CVD) compared to persons without HIV (PWoH). Lipoprotein(a) [Lp(a)] is a known atherosclerotic risk factor in PWoH, but there are no studies investigating Lp(a) and peri-coronary inflammation. OBJECTIVE: To investigate whether Lp(a) is associated with peri-coronary inflammation as assessed by the fat attenuation index (FAI) and activated monocytes and T lymphocytes in PWH and PWoH. METHODS: We measured plasma levels of Lp(a) at study entry in 58 PWH and 21 PWoH without CVD and who had FAI measurements. Associations of Lp(a) with FAI values of the right coronary artery (RCA) and left anterior descending artery were evaluated using multivariable regression models adjusted for potential confounders. Correlations between Lp(a) levels and systemic inflammatory markers and immune cell subsets were examined. RESULTS: Lp(a) was associated with greater peri-coronary inflammation among PWH compared to PWoH (ß=1.73, P=0.019) in the RCA, in adjusted models. Significant correlations were observed with certain inflammatory markers (tumor necrosis factor receptor [TNFR]-I, b=0.295, P<0.001; TNFR-II, b=0.270, P=0.002; high-sensitivity C-reactive protein, b=0.195, P=0.028). Significant correlations were found between Lp(a) levels and several markers of monocyte activation: CD16 -CD163+ (b= -0.199, P=0.024), and CD16 -DR+ MFI (b= -0.179, P=0.042) and T cell subset CD38+CD4+ TEMRA (b= 0.177, P= 0.044). CONCLUSIONS: Lp(a) was associated with greater peri-coronary inflammation in the RCA in PWH compared to PWoH, as well as with select systemic inflammatory markers and specific subsets of immune cells in peripheral circulation.

Cardiometabolic risk factors among HIV patients on antiretroviral therapy.

BACKGROUND: HIV and combination antiretroviral therapy (cART) may increase cardiovascular disease (CVD) risk. We assessed the early effects of cART on CVD risk markers in a population with presumed low CVD risk. METHODS: Adult patients (n=118) in Lusaka, Zambia were recruited at the time of initiation of cART for HIV/AIDS. Cardiometabolic risk factors were measured before and 90 days after starting cART. Participants were grouped according to cART regimens: Zidovudine + Lamivudine + Nevirapine (n=58); Stavudine + Lamivudine + Nevirapine (n=43); and 'other' (Zidovudine + Lamivudine + Efavirenz, Stavudine + Lamivudine + Efavirenz, Tenofovir + Emtricitabine + Efavirenz or Tenofovir + Emtricitabine + Nevirapine, n=17). ANOVA was used to test whether changes in cardiometabolic risk markers varied by cART regimen. RESULTS: From baseline to 90 days after initiation of cART, the prevalence of low levels of high-density lipoprotein cholesterol (<1.04 mmol/L for men and <1.30 mmol/L for women) significantly decreased (78.8% vs. 34.8%, P<0.001) while elevated total cholesterol (TC ≥5.18 mmol/L, 5.1% vs. 11.9%, P=0.03) and the homeostasis model assessment of insulin resistance ≥3.0 (1.7% vs. 17.0%, P<0.001) significantly increased. The prevalence of TC:HDL-c ratio ≥5.0 significantly decreased (44.9% vs. 6.8%, P<0.001). These changes in cardiometabolic risk markers were independent of the cART regimen. CONCLUSION: Our results suggest that short-term cART is associated with a cardioprotective lipid profile in Zambia and a tendency towards insulin resistance regardless of the cART regimen.

The Relationship Between Impaired Coronary Endothelial Function and Systemic Markers of Inflammation in People Living With HIV.

BACKGROUND: People with HIV (PWH) are at an increased risk of cardiovascular disease, partially believed to be related to chronically elevated systemic inflammation. Abnormal systemic endothelial function (SEF) and coronary endothelial function (CEF) develop early in atherogenesis and predict adverse events. It is unknown whether abnormal CEF is related to systemic inflammation in PWH. METHODS: In this substudy of a prior randomized controlled trial in PWH without prior clinical coronary artery disease suppressed on antiretroviral therapy with CEF as a primary end point (N = 82), we investigated the associations between baseline serum markers of inflammation and adhesion and baseline CEF, assessed by noninvasive MRI measures of percentage changes in coronary blood flow and cross-sectional area during isometric handgrip exercise, and SEF using brachial ultrasound for flow-mediated dilation. We also evaluated whether baseline marker levels were associated with CEF after 8 weeks in the placebo group (N = 40). RESULTS: CEF measures were abnormal at baseline, based on trial entry criteria. A higher value of CEF was directly associated with levels of interleukin 10, whereas CEF at baseline was inversely associated with E-selectin. Worse CEF at 8 weeks was directly associated with baseline tumor necrosis factor alpha, intercellular adhesion molecule 1, C-reactive protein, interferon gamma and sICAM-3. SEF at baseline or 8 weeks was not associated with any baseline markers. CONCLUSION: Coronary but not systemic endothelial dysfunction was significantly associated with select markers of inflammation and adhesion in PWH. Furthermore, CEF but not SEF at 8 weeks was associated with baseline levels of inflammation. Our findings suggest that abnormal CEF and systemic markers of inflammation are linked in PWH.

Association of Soluble Markers of Inflammation With Peri-coronary Artery Inflammation in People With and Without HIV Infection and Without Cardiovascular Disease.

Background: Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown. Methods: Plasma levels of inflammatory markers were measured in 58 PWH and 16 controls without current symptoms or prior known CVD who underwent coronary computed tomography angiography and had FAI measurements. A cross-sectional analysis was performed, and associations of markers with FAI values of the right coronary artery (RCA) and left anterior descending artery (LAD) were assessed using multivariable regression models adjusted for the potential confounders age, sex, race, low-density lipoprotein cholesterol, body mass index, and use of lipid-lowering medication. Results: Several inflammatory markers had significant associations with RCA or LAD FAI in adjusted models, including sCD14, sCD163, TNFR-I, and TNFR-II, CCL5, CX3CL1, IP-10. Conclusions: The associations between indices of systemic and peri-coronary inflammation are novel and suggest that these systemic markers and FAI together are promising noninvasive biomarkers that can be applied to assess asymptomatic CVD in people with and without HIV; they also may be useful tools to evaluate effects of anti-inflammatory interventions.

Assessment of coronary inflammation in antiretroviral treated people with HIV infection and active HIV/hepatitis C virus co-infection.

OBJECTIVE: People with HIV (PWH) and co-infected with hepatitis C virus (PWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary computed tomography angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PWH + HCV population. We tested whether peri-coronary inflammation is increased in PWH or PWH + HCV, and whether inflammation changes over time. DESIGN: Cross-sectional analysis to determine FAI differences among groups. Longitudinal analysis in PWH to assess changes in inflammation over time. METHODS: Age-matched and sex-matched seropositive groups (PWH and PWH + HCV) virologically suppressed on antiretroviral therapy, HCV viremic, and without prior CVD and matched controls underwent CCTA. Peri-coronary FAI was measured around the proximal right coronary artery (RCA) and left anterior descending artery (LAD). Follow-up CCTA was performed in 22 PWH after 20.6-27.4 months. RESULTS: A total of 101 participants (48 women) were studied (60 PWH, 19 PWH + HCV and 22 controls). In adjusted analyses, peri-coronary FAI did not differ between seropositive groups and controls. Low attenuation coronary plaque was significantly less common in seropositive groups compared with controls (LAD, P = 0.035; and RCA, P = 0.017, respectively). Peri-coronary FAI values significantly progressed between baseline and follow-up in PWH (RCA: P = 0.001, LAD: P = <0.001). CONCLUSION: PWH and PWH + HCV without history of CVD do not have significantly worse peri-coronary inflammation, assessed by FAI, compared with matched controls. However, peri-coronary inflammation in mono-infected PWH significantly increased over approximately 22 months. FAI measures may be an important imaging biomarker for tracking asymptomatic CVD progression in PWH.

Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution.

BACKGROUND: People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. SETTING: Prospective cohort study. METHODS: PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables. RESULTS: Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = -0.31, P = 0.014), hip circumference (R = -0.27, P = 0.037), and subcutaneous fat area (R = -0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. CONCLUSION: Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Association of hepatitis C infection and acute coronary syndrome: A case-control study.

ABSTRACT: Infections with hepatitis C virus (HCV) represent a substantial national and international public health burden. HCV has been associated with numerous extrahepatic conditions and can lead to metabolic derangements that are associated with atherosclerosis and cardiovascular disease. We investigated whether HCV infection is associated with an increased number of acute coronary syndrome (ACS) events among hospitalized patients in an inner-city tertiary hospital.We performed a matched (age, sex, and race/ethnicity) case-control study on patients at least 18 years old admitted to inpatient medical and cardiac services at the University of Maryland Medical Center from 2015 through 2018. The primary outcome was ACS and the primary exposure was HCV infection. Covariates of interest included: alcohol use, tobacco use, illicit drug use, hypertension, diabetes mellitus, human immunodeficiency virus infection, body mass index, dyslipidemia, and family history of coronary heart disease. Covariates with significant associations with both exposure and outcome in bivariate analyses were included in the multivariable analyses of the final adjusted model.There were 1555 cases and 3110 controls included in the final sample. Almost 2% of cases and 2.4% of controls were HCV infected. In adjusted models, there was no significant association found between experiencing an ACS event in those with HCV infection compared to those without HCV infection (odds ratio 0.71, 95% confidence interval 0.45-1.11).We found no significant association between HCV infection and ACS in our study population. However, given the mixed existing literature, the association between HCV and ACS warrants further investigation in future prospective cohort and/or interventional studies.

The Role of Multimodality Imaging in HIV-Associated Cardiomyopathy.

Despite marked advances in therapeutics, HIV infection remains a leading cause of morbidity and mortality worldwide. HIV infection is associated with cardiovascular complications including myocardial dysfunction. The description of HIV-associated cardiomyopathy (HIVAC) has evolved over time from a predominantly dilated cardiomyopathy with systolic dysfunction to one of subclinical diastolic dysfunction. Multimodality cardiovascular imaging plays an integral role in our understanding of the etiology and pathogenesis of HIVAC. Such imaging is also essential in the evaluation of individuals with chronic HIV disease who present with cardiac symptoms, especially of heart failure. In the present review, we will highlight current evidence for the role of multimodality imaging in establishing the diagnosis, etiology and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis.

A randomized, placebo-controlled, double-blinded clinical trial of colchicine to improve vascular health in people living with HIV.

OBJECTIVES: People living with HIV (PWH) experience an increased burden of coronary artery disease (CAD) believed to be related, in part, to an interplay of chronically increased inflammation and traditional risk factors. Recent trials suggest cardiovascular benefits of the anti-inflammatory, colchicine, in HIV-seronegative CAD patients. However, the impact of colchicine on impaired vascular health, as measured by coronary endothelial function (CEF), an independent contributor to CAD, has not been studied in PWH. We tested the hypothesis that colchicine improves vascular health in PWH. DESIGN: This was a randomized, placebo-controlled, double-blinded trial in 81 PWH to test whether low-dose colchicine (0.6 mg daily) improves CEF over 8-24 weeks. METHODS: Coronary and systemic endothelial function and serum inflammatory markers were measured at baseline, and at 8 and 24 weeks. The primary endpoint was CEF, measured as the change in coronary blood flow from rest to that during an isometric handgrip exercise, an endothelial-dependent stressor, measured with non-invasive MRI at 8 weeks. RESULTS: Colchicine was well tolerated and not associated with increased adverse events. However, there were no significant improvements in coronary or systemic endothelial function or reductions in serum inflammatory markers at 8 or 24 weeks with colchicine as compared to placebo. CONCLUSIONS: In PWH with no history of CAD, low-dose colchicine was well tolerated but did not improve impaired coronary endothelial function, a predictor of cardiovascular events. These findings suggest that this anti-inflammatory approach using colchicine in PWH does not improve vascular health, the central, early driver of coronary atherosclerosis.

Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review.

Hepatitis C virus (HCV) infects 180 million people worldwide and over 4 million people in the United States. HCV infection is a major cause of chronic liver disease and is recognized as a risk factor for clinical cardiovascular disease (CVD). Many studies have shown increased prevalence of cardiac and inflammatory biomarkers in patients with chronic HCV infection (CHC), and though these markers may be used to risk stratify people for cardiac disease in the general population their role in the HCV population is unknown. Patients with CHC have elevated cardiac and inflammatory biomarkers compared to noninfected controls which may play a role in CVD risk stratification. We undertook a systematic review of inflammatory and cardiac biomarkers in people with HCV infection with a focus on the effect of CHC on serum levels of these markers and their utility as predictors of CVD in this population. Medline, EMBASE, and Cochrane databases were searched for relevant articles until June 2019. A total of 2430 results were reviewed with 115 studies included. Our review revealed that HCV infection significantly alters serum levels of markers of inflammation, endothelial function, and cardiac dysfunction prior to HCV treatment, and some of which may change in response to HCV therapy. Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV-infected patients contributing to increased CVD risk.

Peripheral PD-1+ T Cells Co-expressing Inhibitory Receptors Predict SVR With Ultra Short Duration DAA Therapy in HCV Infection.

Direct acting antiviral (DAA) regimens of 12 weeks result in HCV clearance in vast majority of patients across genotypes. We previously demonstrated an ultra-short regimen of 4 weeks DAA cleared HCV in a subset of patients. Here, we hypothesized that individual level of antiviral immunity differentially influenced viral clearance and investigated biomarkers of a successful response. Cohorts of HCV patients treated for 4 weeks with DAA therapy who either achieved sustained virologic response (SVR) or relapsed were compared at baseline and at end of therapy (EOT) for immune cell phenotypes and HCV specific immunity. Higher levels of PD-1+ CD8+ and CD4+ T lymphocytes co-expressing inhibitory receptors (IR) were present at baseline and at EOT in HCV patients who eventually achieved SVR compared with those who relpased. HCV specific CD8+ T cells were predominantly contained within these IR expressing PD-1+ subsets. Patients in the SVR group had significantly higher CD8+ T cell degranulation in response to HCV peptides at baseline and higher levels of cytokine producing T cells at EOT time-point, relative to those who relapsed. In ex vivo cultures, PD-1+CD160+ CD8+ T cells had higher HCV specific degranulation and PD-1+2B4+ CD8+ T cells had higher cytokine expression (IFNγ+TNFα+ or IFNγ+CD107a+) compared with single or no IR expressing subsets, indicating higher virus specific functional capacity of these subsets. Receiver operating characteristics curve (ROC) for baseline circulating frequencies of PD-1+CD160+, PD-1+Tim-3+ CD8+ T cells and PD-1+CD160+, PD-1+Blimp-1+, PD-1-CTLA4+ CD4+ T cells respectively, had associated C-statistics of 0.8214 and 0.9451 for discriminatin of patients who successfully cleared HCV with 4 weeks treatment. Thus, PD-1+ virus-specific CD8+ T cell subsets with cytotoxic capacity are present in a subset of chronic HCV infected individuals that associate with ability to achieve SVR, indicating role of immunity in DAA mediated viral clearance with short duration therapy.

Global burden of atherosclerotic cardiovascular disease in people with hepatitis C virus infection: a systematic review, meta-analysis, and modelling study.

BACKGROUND: More than 70 million people worldwide are estimated to have hepatitis C virus (HCV) infection. Emerging evidence indicates an association between HCV and atherosclerotic cardiovascular disease. We aimed to determine the association between HCV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HCV. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, Ovid Global Health, and Web of Science databases from inception to May 9, 2018, without language restrictions, for longitudinal studies that evaluated the risk ratio (RR) of cardiovascular disease in people with HCV compared with those without HCV. Two investigators independently reviewed and extracted data from published reports. The main outcome was cardiovascular disease, defined as hospital admission with, or mortality from, acute myocardial infarction or stroke. We calculated the pooled RR of cardiovascular disease associated with HCV using a random-effects model. Additionally, we calculated the population attributable fraction and disability-adjusted life-years (DALYs) from HCV-associated cardiovascular disease at the national, regional, and global level. We also used age-stratified and sex-stratified HCV prevalence estimates and cardiovascular DALYs for 100 countries to estimate country-level burden associated with HCV. This study is registered with PROSPERO, number CRD42018091857. FINDINGS: Our search identified 16 639 records, of which 36 studies were included for analysis, including 341 739 people with HCV. The pooled RR for cardiovascular disease was 1·28 (95% CI 1·18-1·39). Globally, 1·5 million (95% CI 0·9-2·1) DALYs per year were lost due to HCV-associated cardiovascular disease. Low-income and middle-income countries had the highest disease burden with south Asian, eastern European, north African, and Middle Eastern regions accounting for two-thirds of all HCV-associated cardiovascular DALYs. INTERPRETATION: HCV infection is associated with an increased risk of cardiovascular disease. The global burden of cardiovascular disease associated with HCV infection was responsible for 1·5 million DALYs, with the highest burden in low-income and middle-income countries. FUNDING: British Heart Foundation and Wellcome Trust.

Can routine clinical markers be used longitudinally to monitor antiretroviral therapy success in resource-limited settings?

Although routine clinical markers are used routinely to determine the stage of human immunodeficiency virus (HIV) disease, their use in monitoring response to antiretroviral therapy is poorly defined. Selected clinical markers were evaluated for their ability to predict first-line antiretroviral therapy success. No clinically meaningful variables were identified that predicted virologic or immunological success, implying that the CD4+ cell count and HIV type 1 RNA level data are required for optimal management of antiretroviral therapy.

Elbasvir/grazoprevir for treatment of chronic hepatitis C virus infection.

Hepatitis C is the leading cause of progressive liver fibrosis worldwide and results in cirrhosis, liver cancer, liver failure and death. Successful treatment for hepatitis C virus (HCV) has rapidly evolved in recent years to a well-tolerated, highly efficacious all-oral therapy. Elbasvir/grazoprevir (Zepatier) is the newest of the oral combinations of HCV direct-acting agents that was approved by the US Federal Drug Administration. This review focuses on the pharmacology, mechanism of action and clinical trial data that support the use of this new combination treatment for HCV infection. The data suggest that Zepatier offers an excellent treatment efficacy, safety and tolerability in HCV treatment naïve and experienced patients and those with and without cirrhosis across multiple genotypes. Also, it has the selective advantage of safety and efficacy in patients with renal disease, especially in those with end-stage renal disease and/or hemodialysis patients.

Risk of Cardiovascular Disease Due to Chronic Hepatitis C Infection: A Review.

Hepatitis C (HCV) infection has an estimated global prevalence of 2.5%, causing chronic liver disease in 170 million people worldwide. Recent data has identified HCV infection as a risk factor for subclinical and clinical cardiovascular disease (CVD), but these data have been mixed and whether HCV is an independent risk factor for development of CVD remains controversial. In this review, we present the literature regarding the association of HCV with subclinical and clinical CVD and the possible underlying mechanisms leading to increased CVD among those infected with HCV. HCV infection leads to increased CVD via direct and indirect mechanisms with chronic inflammation, endothelial dysfunction and direct invasion of the arterial wall cited as possible mechanisms. Our review showed that HCV infection, particularly chronic HCV infection, appears to lead to increased subclinical CVD most consistently and potentially also to increased clinical CVD outcomes, leading to increased morbidity and mortality. Furthermore, the majority of studies evaluating the impact of HCV therapy on CVD morbidity and mortality showed an improvement in subclinical and clinical CVD endpoints in patients who were successfully treated and achieved sustained viral suppression. These results are of particular interest following the development of new direct antiviral agents which have made HCV eradication simple and feasible for many more patients globally, and in doing so may possibly reduce CVD morbidity and mortality in those with chronic HCV infection.