Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial.

Importance: In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin reduced noncalcified plaque (NCP) volume, but specific protein and gene pathways contributing to changes in coronary plaque remain unknown.

Objective: To use targeted discovery proteomics and transcriptomics approaches to interrogate biological pathways beyond low-density lipoprotein cholesterol (LDL-C), relating statin outcomes to reduce NCP volume and promote plaque stabilization among people with HIV (PWH).

Design, Setting, And Participants: This was a post hoc analysis of the double-blind, placebo-controlled, REPRIEVE randomized clinical trial.

Association of T-cell subtypes with macrophage-specific arterial infiltration in people with HIV.

People with human immunodeficiency virus (HIV, PWH) face an increased risk of cardiovascular disease (CVD) compared to the general population. We previously demonstrated that people with (versus without) HIV have higher macrophage-specific arterial infiltration in relation to systemic monocyte activation. We now show that select T lymphocyte subpopulations (naïve CD4 + , effector memory CD4 + , and central memory CD8 + ) are differentially associated with macrophage-specific arterial infiltration among participants with versus without HIV, with evidence of interaction by HIV status.

Cytomegalovirus IgG is Associated With Physical Function But Not Muscle Density in People With HIV.

Background: Cytomegalovirus (CMV) seropositivity is associated with poor outcomes, including physical function impairment, in people without HIV. We examined associations between CMV IgG titer and physical function in virologically suppressed people with HIV (PWH).

Methods: REPRIEVE is a double-blind randomized trial evaluating pitavastatin for primary prevention of atherosclerotic cardiovascular disease in PWH.

Beyond Undetectable: Modeling the Clinical Benefit of Improved Antiretroviral Adherence in Persons With Human Immunodeficiency Virus With Virologic Suppression.

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown.

Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials.

Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People With Treated Human Immunodeficiency Virus.

Background: Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting.

Methods: In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression.

Results: Higher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition.

Variant With Multiple Resistance Mutations Detected in an Immunocompromised Patient Receiving Atovaquone Prophylaxis.

We report genomic sequences with multiple mutations in the atovaquone-target region of cytochrome b, including a newly identified Y272S mutation, plus 1 mutation of undetermined significance in the azithromycin-associated ribosomal protein L4. The parasite was sequenced from an immunocompromised patient on prophylactic atovaquone for pneumonia before diagnosis of babesiosis.

Effect of host factors and COVID-19 infection on the humoral immune repertoire in treated HIV.

People with HIV (PWH) appear to be at higher risk for suboptimal pathogen responses and for worse COVID-19 outcomes, but the effects of host factors and COVID-19 on the humoral repertoire remain unclear. We assessed the antibody isotype/subclass and Fc-receptor binding Luminex arrays of non-SARS-CoV-2 and SARS-CoV-2 humoral responses among antiretroviral therapy-treated (ART-treated) PWH. Among the entire cohort, COVID-19 infection was associated with higher cytomegalovirus (CMV) responses (vs.

Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV).

Background: Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque.

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk.

Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus.

Background: Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH).

Methods: Participants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH.

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use.

Background: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes.

Methods: We studied plasma immune activation biomarkers, viral load, and CD4 and CD8 cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks.

Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection.

Background: Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum period.

Methods: Women with HIV initiating antiretroviral therapy (ART) in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (n = 54).

Clinical consequences of asymptomatic cytomegalovirus in treated human immunodeficency virus infection.

Purpose Of Review: Despite antiretroviral therapy (ART)-mediated viral suppression, people with human immunodeficiency virus (HIV) (PWH) have increased morbidity and mortality. Immune activation and inflammation persist on ART and predict these complications. Over 90% of PWH have cytomegalovirus (CMV) co-infection, and CMV is considered a plausible contributor to this persistent immune activation.

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience.

Background: Heplisav-B, a hepatitis B virus (HBV) vaccine with an immunostimulatory adjuvant, was FDA approved in 2017 for adults ≥18 years. In randomized controlled trials, Heplisav-B demonstrated seroprotection rates (SPR) of 90%-95% versus 65%-80% for Engerix-B. No studies have included people with HIV (PWH), and the SPR and its predictors in this population are unknown.

Abnormal Levels of Some Biomarkers of Immune Activation Despite Very Early Treatment of Human Immunodeficiency Virus.

Background: Despite early antiretroviral therapy (ART), ART-suppressed people with human immunodeficiency virus (HIV) (PWH) remain at higher risk for infections and infection-related cancers than the general population. The immunologic pathways that remain abnormal in this setting, potentially contributing to these complications, are unclear.

Methods: ART-suppressed PWH and HIV-negative controls, all cytomegalovirus seropositive and enriched for HIV risk factors, were sampled from an influenza vaccine responsiveness study.

Ross Procedure Following a Dislodged Transcatheter Aortic Valve Replacement.

A 36-year-old pregnant woman with a history of rheumatic heart disease and prior aortic valve replacement and mitral valve repair presented to an outside hospital with severe aortic stenosis. The patient had a cardiac arrest upon labor induction and underwent a transcatheter aortic valve replacement (TAVR), which dislodged two days later. Five months later, the patient underwent removal of the dislodged TAVR and a Ross procedure at the authors' institution.

Novel predictors of mild paravalvular aortic regurgitation in SAPIEN 3 transcatheter aortic valve implantation.

Aims: Paravalvular leak (PVL) remains an important issue in TAVI. The Edwards SAPIEN 3 (S3) valve has reduced PVL but in up to one third of patients mild leak remains. Our study aimed to identify predictors of mild PVL after TAVI with the S3 valve.

Bioprosthetic aortic valve replacement: Revisiting prosthesis choice in patients younger than 50 years old.

Objective: Aortic prosthesis choice is controversial in young adults because robust comparative outcome data are lacking. We therefore compared mortality and morbidity in young adults after bioprosthetic versus mechanical aortic valve replacement.

Methods: This was a retrospective analysis of 5111 patients aged 18 to 50 years undergoing primary aortic valve replacement in California and New York State from 1997 to 2006.

Survival and long-term outcomes after mitral valve replacement in patients aged 18 to 50 years.

Objective: To provide long-term data on survival and major morbidity after mitral valve replacement in patients aged 18 to 50 years.

Methods: Retrospective analysis of 2727 patients aged 18 to 50 years who underwent isolated mitral replacement in California and New York from 1997 to 2006. Median follow-up time was 12.

Feasibility of Intraoperative Extubation in Pediatric Heart Transplantation.

Based on described benefits of fast-tracking and early extubation in children undergoing congenital heart surgery, we applied this concept to selected children following uncomplicated orthotopic heart transplantation (OHT). In this case series, we report four patients who were extubated immediately after surgery in the operating room. A mild respiratory acidosis and hypercapnia were noted on the initial arterial blood gases, were well tolerated, and were normalized within 6 to 12 hours.

Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study.

Objective: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.

Design: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA View Article and Find Full Text PDF

Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial.

Background: Several direct-acting antivirals for chronic hepatitis C virus (HCV) infection are available, but they are limited by tolerability and dosing schedules. Once-daily daclatasvir, a potent NS5A replication complex inhibitor, was generally well tolerated in phase 1 studies. We assessed daclatasvir in combination with pegylated interferon (peginterferon) and ribavirin for chronic HCV.

Atazanavir and atazanavir/ritonavir pharmacokinetics in HIV-infected infants, children, and adolescents.

Objective: To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years.

Design: A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children.

Setting: Sites in the United States and South Africa.

Prevalence and clinical significance of HIV drug resistance mutations by ultra-deep sequencing in antiretroviral-naïve subjects in the CASTLE study.

Background: CASTLE compared the efficacy of atazanavir/ritonavir with lopinavir/ritonavir, each in combination with tenofovir-emtricitabine in ARV-naïve subjects from 5 continents.

Objectives: Determine the baseline rate and clinical significance of TDR mutations using ultra-deep sequencing (UDS) in ARV-naïve subjects in CASTLE.

Methods: A case control study was performed on baseline samples for all 53 subjects with virologic failures (VF) at Week 48 and 95 subjects with virologic successes (VS) randomly selected and matched by CD4 count and viral load.