Cardiovascular Risk Estimation Is Suboptimal in People With HIV.

Background: Established cardiovascular disease (CVD) risk prediction functions may not accurately predict CVD risk in people with HIV. We assessed the performance of 3 CVD risk prediction functions in 2 HIV cohorts.

Methods And Results: CVD risk scores were calculated in the Mass General Brigham and Kaiser Permanente Northern California HIV cohorts, using the American College of Cardiology/American Heart Association atherosclerotic CVD function, the FHS (Framingham Heart Study) hard coronary heart disease function and the Framingham Heart Study hard CVD function.

Cardiometabolic health in people with HIV: expert consensus review.

Objectives: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts.

Methods: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations.

Changes in Body Mass Index with Longer-term Integrase Inhibitor Use: A Longitudinal Analysis of Data from the Randomized Trial to Prevent Vascular Events in Human Immunodeficiency Virus (REPRIEVE).

Over 2-years of follow-up, integrase strand transfer inhibitor (INSTI)-use was associated with weight gain among those on an INSTI <2 years at entry (+0.27 kg/m2/year; 95% confidence interval [CI], .22 to .

Metabolic Consequences of Antiretroviral Therapy.

Purpose Of Review: This review reports on published studies describing metabolic changes associated with antiretroviral therapy (ART) to treat HIV disease including a historical perspective of earlier ART agents, but with the main focus on newer ART agents currently in use.

Recent Findings: Studies from different countries around the world have shown that integrase inhibitor (INSTI)-based regimens as well as tenofovir alafenamide (TAF) are associated with weight gain, with women and people of black race at especially high risk. Some studies preliminarily suggest worsened metabolic outcomes associated with this weight gain including adverse effects on glucose homeostasis.

Changes in Inflammatory and Atherogenesis Biomarkers With the 2-Drug Regimen Dolutegravir Plus Lamivudine in Antiretroviral Therapy-Experienced, Virologically Suppressed People With HIV-1: A Systematic Literature Review.

Background: The 2-drug regimen dolutegravir plus lamivudine has demonstrated long-term noninferior efficacy vs 3-/4-drug regimens (3/4DRs) in phase 3 trials. This systematic literature review summarizes clinical trial and real-world evidence evaluating impact of dolutegravir plus lamivudine on inflammatory and atherogenesis biomarkers in people with human immunodeficiency virus type 1 (PWH).

Methods: Using Ovid MEDLINE, Embase, PubMed, and Cochrane library databases and conference proceedings, we searched for studies published from 1 January 2013 to 14 July 2021, reporting changes in inflammatory and atherogenesis biomarkers with dolutegravir plus lamivudine in antiretroviral therapy-experienced, virologically suppressed PWH aged ≥18 years.

Assessment of Obesity and Cardiometabolic Status by Integrase Inhibitor Use in REPRIEVE: A Propensity-Weighted Analysis of a Multinational Primary Cardiovascular Prevention Cohort of People With Human Immunodeficiency Virus.

Background: Emerging data demonstrate that the use of integrase inhibitor (INSTI)-based antiretroviral treatment (ART) is associated with increased weight, but the cardiometabolic health consequences of increased weight remains poorly understood.

Methods: This analysis examined INSTI use (>6 months) at entry among REPRIEVE participants enrolled in High Income and Latin America/Caribbean Global Burden of Disease regions. Primary analyses used linear and logistic regression; secondary analyses used quantile regression to examine differences across the full data distribution.

Severe autoimmune hemolytic anemia following receipt of SARS-CoV-2 mRNA vaccine.

Background: Large clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia.

Case Presentation: Here we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine.

Visceral Adiposity and Severe COVID-19 Disease: Application of an Artificial Intelligence Algorithm to Improve Clinical Risk Prediction.

Background: Obesity has been linked to severe clinical outcomes among people who are hospitalized with coronavirus disease 2019 (COVID-19). We tested the hypothesis that visceral adipose tissue (VAT) is associated with severe outcomes in patients hospitalized with COVID-19, independent of body mass index (BMI).

Methods: We analyzed data from the Massachusetts General Hospital COVID-19 Data Registry, which included patients admitted with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection from March 11 to May 4, 2020.

A neurobiological link between transportation noise exposure and metabolic disease in humans.

Background: Chronic transportation noise exposure associates with cardiovascular events through a link involving heightened stress-associated neurobiological activity (as amygdalar metabolic activity, AmygA) on F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT). Increased AmygA also associates with greater visceral adipose tissue (VAT) and type 2 diabetes mellitus (DM). While relationships between noise exposure and VAT and DM have been reported, the underlying mechanisms remain incompletely understood.

Changes in Body Mass Index Associated with Antiretroviral Regimen Switch Among Treatment-Experienced, Virologically Suppressed People Living with HIV in the United States.

With obesity on the rise among people living with HIV (PLWH), there is growing concern that weight gain may result as an undesired effect of antiretroviral therapy (ART). This analysis sought to assess the association between ART regimens and changes in body mass index (BMI) among ART-experienced, virologically suppressed PLWH. ART-experienced, virologically suppressed PLWH ≥18 years of age in the Observational Pharmacoepidemiology Research and Analysis (OPERA) cohort were included for analysis if prescribed a new regimen containing one of the following core agents: dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), raltegravir (RAL), rilpivirine (RPV), or boosted darunavir (bDRV), for the first time between August 1, 2013 and December 31, 2017.

Gastrointestinal Dysfunction and HIV Comorbidities.

Purpose Of Review: Gut dysfunction and resulting chronic low-grade inflammation have been linked to metabolic and chronic diseases in the general population. In this review, we present recently published studies of HIV-associated gut dysfunction and comorbidities including obesity, diabetes, cardiovascular disease, liver disease, and neurocognitive disease.

Recent Findings: Biomarkers of microbial translocation, dysbiosis, or intestinal epithelial integrity have been used to investigate relationships between HIV-associated gut dysfunction and metabolic, cardiovascular, and neurologic complications.

Pro-Inflammatory Interleukin-18 is Associated with Hepatic Steatosis and Elevated Liver Enzymes in People with HIV Monoinfection.

People with HIV (PWH) are at an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Interleukin (IL)-18 is regulated by inflammasomes in response to pathogens and danger signals and has been implicated in both the pathogenesis of NAFLD and HIV disease progression. We hypothesized that increased IL-18 may be associated with NAFLD and liver injury in PWH.

EGFR/ErbB2-Targeting Lapatinib Therapy for Aggressive Prolactinomas.

Context: Approximately 10% to 20% of prolactinomas are resistant to dopamine agonist therapy. The ErbB signaling pathway may drive aggressive prolactinoma behavior.

Objective: We evaluated lapatinib, an ErbB1-epidermal growth factor receptor (EGFR)/ErbB2 or human EGFR2 (HER2) tyrosine kinase inhibitor (TKI), in aggressive prolactinomas.

Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial.

Background: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.

Methods: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.

Differential Plasma Protein Regulation and Statin Effects in Human Immunodeficiency Virus (HIV)-Infected and Non-HIV-Infected Patients Utilizing a Proteomics Approach.

Background: People with human immunodeficiency virus (PWH) demonstrate increased atherosclerotic cardiovascular disease (ASCVD). Statins are being studied to prevent ASCVD in human immunodeficiency virus (HIV), but little is known regarding the effects of statins on a broad range of inflammatory and cardiovascular proteins in this population.

Methods: We used a highly specific discovery proteomic approach (Protein Extension Assay), to determine statin effects on over 350 plasma proteins in relevant ASCVD pathways among HIV and non-HIV groups.

Measures of Adipose Tissue Redistribution and Atherosclerotic Coronary Plaque in HIV.

Objective: People with HIV (PWH) who are well treated on antiretroviral therapy remain at increased risk for body composition changes, including increased visceral adipose tissue (VAT) and reduced subcutaneous adipose tissue (SAT), as well as increased cardiovascular disease (CVD). The relationship between adipose compartments and coronary disease is not well understood among PWH.

Methods: A total of 148 PWH and 68 uninfected individuals without CVD were well phenotyped for VAT and SAT via single-section abdominal computed tomography (CT) at L4.

Low vitamin D is associated with coronary atherosclerosis in women with HIV.

Background: Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD). While vitamin D deficiency has been associated with CVD in observational studies in the general population, there are limited data in PLWH.

Individual coronary plaque changes on serial CT angiography: Within-patient heterogeneity, natural history, and statin effects in HIV.

Background: It is not known how the volume and composition of individual coronary plaques change over time in HIV-infected people and whether statins influence these changes.

Methods: We included forty adults with HIV and subclinical coronary atherosclerosis who participated in a randomized controlled trial of placebo vs. atorvastatin.

Caspase-1 Activation Is Related With HIV-Associated Atherosclerosis in an HIV Transgenic Mouse Model and HIV Patient Cohort.

Objective: Atherosclerotic cardiovascular disease (ASCVD) is an increasing cause of morbidity and mortality in people with HIV since the introduction of combination antiretroviral therapy. Despite recent advances in our understanding of HIV ASCVD, controversy still exists on whether this increased risk of ASCVD is due to chronic HIV infection or other risk factors. Mounting biomarker studies indicate a role of monocyte/macrophage activation in HIV ASCVD; however, little is known about the mechanisms through which HIV infection mediates monocyte/macrophage activation in such a way as to engender accelerated atherogenesis.

Anti-Inflammatory Interleukin 10 Inversely Relates to Coronary Atherosclerosis in Persons With Human Immunodeficiency Virus.

Interleukin 10 (IL-10) is an anti-inflammatory cytokine that may be protective against coronary atherosclerosis. In an observational study of persons with human immunodeficiency virus (PWH) and uninfected controls, IL-10 was measured in serum samples by means of enzyme-linked immunosorbent assay, and coronary atherosclerosis was assessed using computed tomographic angiography. Among PWH, a 10-fold decrease in IL-10 was associated with a 2.

Obesity and Fat Metabolism in Human Immunodeficiency Virus-Infected Individuals: Immunopathogenic Mechanisms and Clinical Implications.

Metabolic complications relating to complex effects of viral and immune-mediated mechanisms are now a focus of clinical care among persons living with human immunodeficiency virus (PLHIV), and obesity is emerging as a critical problem. To address knowledge gaps, the US National Institutes of Health sponsored a symposium in May 2018 entitled "Obesity and Fat Metabolism in HIV-infected Individuals." Mechanisms relating to adipose dysfunction and fibrosis, immune function, inflammation, and gastrointestinal integrity were highlighted as contributors to obesity among PLHIV.