MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown.

Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD-PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level.

Ex vivo sensitivity to broadly neutralizing antibodies and anti-CD4 antibody UB-421 of infectious viral isolates from people living with multidrug-resistant HIV.

Background: People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking.

Transcriptionally Active Defective HIV-1 Proviruses and Their Association With Immunological Nonresponse to Antiretroviral Therapy.

A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .

The Association of Air Pollution Exposure With Glucose and Lipid Levels: The Role of an Extreme Air Pollution Event Alongside 2 Decades of Moderate Exposure.

Extreme air pollution events and moderate exposure to fine particulate matter (PM2.5) are associated with increased cardiometabolic risk. The World Trade Center (WTC) Health Program general responder cohort includes responders to the WTC disaster.

Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study.

Objective: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers.

Design: National cohort study.

Setting: Sweden.

Sex-Specific Differences in Clinical Outcomes After Percutaneous Coronary Intervention: Insights from the TAILOR-PCI Trial.

Background TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype-guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of loss-of-function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex-specific analysis of genotyping and associated cardiovascular outcomes from this study.

Obstructive sleep apnoea and left ventricular diastolic dysfunction among first responders to the 9/11 World Trade Center terrorist attack: a cross-sectional study.

Objectives: Obstructive sleep apnoea (OSA) is often linked to cardiovascular disease. A limited number of studies have reported an association between OSA and left ventricular diastolic dysfunction (LVDD). However, prior studies were performed on small patient populations.

Pre-term delivery and long-term risk of heart failure in women: a national cohort and co-sibling study.

Aims: Women who deliver pre-term have higher future risks of hypertension and ischaemic heart disease, but long-term risks of heart failure (HF) are unknown. We examined these risks in a large national cohort.

Methods And Results: All 2 201 284 women with a singleton delivery in Sweden during 1973-2015 were followed up for inpatient or outpatient HF diagnoses through 2015.

Pre-Term Delivery and Risk of Ischemic Heart Disease in Women.

Background: Women who deliver pre-term have been reported to have increased future risks of cardiometabolic disorders. However, their long-term risks of ischemic heart disease (IHD) and whether such risks are due to shared familial factors are unclear. A better understanding of these risks may help improve long-term clinical follow-up and interventions to prevent IHD in women.

The Effect of GS-548351 on the Pharmacokinetics of Midazolam Following Multiple Doses of ANS-6637 in Healthy Adults.

ANS-6637, a pro-drug of GS-548351, is a selective, reversible inhibitor of aldehyde dehydrogenase isoform 2 under development as an anticraving agent for the treatment of substance use disorders. In vitro testing indicates that GS-548351 is an inhibitor and inducer of cytochrome P450 family 3, subfamily A (CYP3A). In this phase 1 single-center, open-label, fixed-sequence drug-drug interaction study we assessed the impact of steady-state GS-548351 on single-dose pharmacokinetics of midazolam, an index substrate for CYP3A.

Metabolic Changes in Chronic Hepatitis C Patients Who Carry IFNL4-ΔG and Achieve Sustained Virologic Response With Direct-Acting Antiviral Therapy.

Background: Clearance of hepatitis C virus (HCV) results in rapid changes in metabolic parameters early in direct-acting antiviral (DAA) therapy. Long-term changes after sustained virologic response (SVR) remain unknown.

Methods: We investigated longitudinal changes in metabolic and inflammatory outcomes in chronic hepatitis C (CHC) patients: low-density lipoprotein (LDL), high-density lipoprotein, triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) using a general linear model for repeated measurements at 5 clinical time points and by human immunodeficiency virus (HIV) coinfection and IFNL4 genotype.

Long-term changes in hepatic fibrosis following hepatitis C viral clearance in patients with and without HIV.

Background: While acute changes in hepatic fibrosis are recognized shortly after achieving sustained virological response (SVR) using direct-acting antiviral therapies, long-term outcomes for the growing population of successfully treated patients with HCV remain uncertain. The aim of this study is to characterize long-term changes in fibrosis following SVR in patients with and without HIV and to identify potential factors associated with progression or regression of fibrosis.

Methods: We completed a prospective longitudinal study of 162 subjects with HCV (34% HIV-coinfected) with pre-treatment fibrosis stage determined by liver biopsy and post-SVR transient elastography.

Association of Preterm Birth With Risk of Ischemic Heart Disease in Adulthood.

Importance: Preterm birth has previously been associated with increased risks of hypertension and diabetes, but not ischemic heart disease (IHD), in adulthood. The reasons for this lack of association with IHD despite associations with its risk factors have been elusive, but may be associated with methodologic issues, such as survivor bias, in prior studies.

Objective: To determine whether preterm birth is associated with an increased risk of IHD in adulthood in a large population-based cohort.

Immunological recovery in T-cell activation after sustained virologic response among HIV positive and HIV negative chronic Hepatitis C patients.

Background: Rapid decreases in activated CD4+ and CD8+ (HLA-DR + and CD38+ co-expressed) T-lymphocytes have been described within 1-2 weeks of initiating direct-acting antiviral (DAA) therapy among chronic Hepatitis C (CHC) patients. However, it is not known whether these changes are maintained past sustained virologic response (SVR), particularly in those who are HIV/HCV-coinfected.

Methods: We investigated the changes in immune parameters of T-lymphocytes from pre-DAA therapy to post-SVR among HIV negative and HIV positive patients with CHC.

Teaching Patients with Advanced Cancer to Self-Advocate: Development and Acceptability of the Strong Together™ Serious Game.

Objective: Serious games are a growing form of psychoeducation, although few studies have evaluated serious games for patients with advanced cancer. The purpose of this study was to develop and assess the initial acceptability of a serious game to teach women with advanced cancer self-advocacy skills, including communication, decision-making, and social connectivity, to improve their quality of life with cancer.

Materials And Methods: We conducted a multistage, user-centered codesign process to develop the content of the game that was consistent with our work on how patients self-advocate and patients' preferences for the game.

Testosterone in Men With Chronic Hepatitis C Infection and After Hepatitis C Viral Clearance.

Background: Hepatitis C virus (HCV) and hepatic dysfunction are associated with low total and free testosterone (TT and FT) and high sex hormone-binding globulin (SHBG). However, little is known about changes in testosterone following successful HCV treatment.

Methods: We evaluated testosterone levels and the prevalence of low testosterone in a cohort of 327 men with chronic HCV infection (human immunodeficiency virus [HIV] coinfection = 150) and in a subset of 85 men with testosterone levels obtained pre-HCV treatment and after sustained virologic response (SVR).

Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine.

Background: Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection. This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication.

Methods: This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers.

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

Background: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.

Methods And Findings: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016).

Magnetic Resonance Elastography Shear Wave Velocity Correlates with Liver Fibrosis and Hepatic Venous Pressure Gradient in Adults with Advanced Liver Disease.

Portal hypertension, an elevation in the hepatic venous pressure gradient (HVPG), can be used to monitor disease progression and response to therapy in cirrhosis. Since obtaining HVPG measurements is invasive, reliable noninvasive methods of assessing portal hypertension are needed. Noninvasive markers of fibrosis, including magnetic resonance elastography (MRE) shear wave velocity, were correlated with histologic fibrosis and HVPG measurements in hepatitis C (HCV) and/or HIV-infected patients with advanced liver disease enrolled in a clinical trial of treatment with simtuzumab, an anti-LOXL2 antibody.

Availability, Use, and Barriers to Cardiac Rehabilitation in LMIC.

Background: Cardiac rehabilitation (CR) is a cornerstone of secondary prevention of ischemic heart disease. It is critically important in low- and middle-income countries (LMIC), where the burden of ischemic heart disease is substantial and growing. However, the availability and utilization of CR in LMIC is not systematically known.

Adverse effects of antiretroviral therapy on liver hepatocytes and endothelium in HIV patients: An ultrastructural perspective.

Human immunodeficiency virus and antiretroviral therapy (ART) together can be far more detrimental to liver cells than either of the two unaided. However, ultrastructural aspects of the synergistic effects of HIV and ART have been understudied. In a patient cohort receiving ART, this study characterizes ultrastructurally sinusoidal degeneration, hepatocytic aberrations, mitochondrial dysfunction, accumulation of bulky lipid droplets (steatosis), and occlusion of sinusoidal lumina.

Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.

Background: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression.

Objectives: The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging.

Methods: Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months.

The prevalence of metabolic syndrome among law enforcement officers who responded to the 9/11 World Trade Center attacks.

Background: Law enforcement officers (LEOs) experience high rates of cardiovascular events compared with the general US population. Metabolic syndrome (MetS) confers an increased risk of cardiovascular disease and all-cause mortality. Data regarding MetS among LEOs are limited.

Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial.

Background: Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed.

Aim: The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease.

Lack of an Effect of Ritonavir Alone and Lopinavir-Ritonavir on the Pharmacokinetics of Fenofibric Acid in Healthy Volunteers.

Study Objective: Because we previously observed a significant 41% reduction in gemfibrozil exposure after 2 weeks of lopinavir-ritonavir administration, we sought to determine the influence of lopinavir-ritonavir and ritonavir alone on the pharmacokinetics of fenofibric acid, an alternative to gemfibrozil for the treatment of elevated triglyceride levels.

Design: Open-label, single-sequence pharmacokinetic study.

Setting: Clinical Research Center at the National Institutes of Health.