Creating a plasma coordination center to support COVID-19 outpatient trials across a national network of hospital blood banks.

Introduction: In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

Methods: A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

Cytokine Storm Syndrome as a Manifestation of Primary HIV Infection.

HIV infection triggers an inflammatory response that manifests as acute retroviral syndrome (ARS) in most individuals infected by HIV. While this syndrome is usually self-limited, primary HIV infection sometimes triggers a fulminant inflammatory process consistent with cytokine storm syndrome (CSS). Many of the key findings of CSS including fever, splenomegaly, and cytopenias are routinely observed in ARS, suggesting CSS may be under recognized in the setting of acute HIV infection.

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy With Blood Pressure and Sustained Hypertension in People With Human Immunodeficiency Virus.

Background: Integrase strand transfer inhibitors (INSTIs) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP).

Methods: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy.

Objective: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).

Design: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4 + T-cell counts greater than 500 cells/μl, and nadir CD4 + T-cell counts greater than 350 cells/μl.

Methods: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55 Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55 Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C).

COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect.

Early antibody treatment, inflammation, and risk of post-COVID conditions.

Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

Background: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection.

Methods: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

Background: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

Study Design And Methods: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.

Heme-Induced Macrophage Phenotype Switching and Impaired Endogenous Opioid Homeostasis Correlate with Chronic Widespread Pain in HIV.

Chronic widespread pain (CWP) is associated with a high rate of disability and decreased quality of life in people with HIV-1 (PWH). We previously showed that PWH with CWP have increased hemolysis and elevated plasma levels of cell-free heme, which correlate with low endogenous opioid levels in leukocytes. Further, we demonstrated that cell-free heme impairs β-endorphin synthesis/release from leukocytes.

Why Wait? The Ethics of Disclosing HIV Screening Results.

Counseling patients on their HIV test results is an important part of undergraduate and graduate medical education. However, many trainees and physicians feel ill prepared to counsel patients on potentially distressing results. We present a case involving early disclosure of a false-positive HIV screening test result to a patient and the downstream effects of this premature disclosure.

Impacts of plasma microbial lipopolysaccharide translocation on B cell perturbations and anti-CD4 autoantibody production in people with HIV on suppressive antiretroviral therapy.

Background: . Up to 20% of people with HIV (PWH) who undergo virologically suppressed antiretroviral therapy (ART) fail to experience complete immune restoration. We recently reported that plasma anti-CD4 IgG (antiCD4IgG) autoantibodies from immune non-responders specifically deplete CD4 + T cells via antibody-dependent cytotoxicity.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

Background: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined.

Methods: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup.

The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.

Background: We recently reveal that anti-CD4 autoantibodies contribute to blunted CD4+ T cell reconstitution in HIV+ individuals on antiretroviral therapy (ART). Cocaine use is common among HIV+ individuals and is associated with accelerated disease progression. However, the mechanisms underlying cocaine-induced immune perturbations remain obscure.

Geospatial Analysis of Time to Human Immunodeficiency Virus (HIV) Diagnosis and Adult HIV Testing Coverage Highlights Areas for Intervention in the US Southeast.

Background: In the United States (US), 44% of people with human immunodeficiency virus (PWH) live in the Southeastern census region; many PWH remain undiagnosed. Novel strategies to inform testing outreach in rural states with dispersed HIV epidemics are needed.

Methods: Alabama state public health HIV testing surveillance data from 2013 to 2017 were used to estimate time from infection to HIV diagnosis using CD4 T-cell depletion modeling, mapped to county.

Early Treatment, Inflammation and Post-COVID Conditions.

Background: Post-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC.

Using publicly available data to identify priority communities for a SARS-CoV-2 testing intervention in a southern U.S. state.

Background: The U.S. Southeast has a high burden of SARS-CoV-2 infections and COVID-19 disease.

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial.

Background: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

Methods: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk.

Hypertension and Cardiovascular Disease Risk Among Individuals With Versus Without HIV.

Background: A high proportion of individuals with HIV have hypertension, and the incidence of cardiovascular disease (CVD) is high in individuals with HIV.

Methods: We determined if the association between hypertension and CVD, including acute myocardial infarction (AMI), stroke, and heart failure, differs between individuals with and without HIV. We analyzed data for 108 980 adults with HIV matched (1:4) to 435 920 adults without HIV in 2011 to 2019 from the Marketscan database, which includes US adults with health insurance.

Brief Report: Intracellular Cystatin B Levels Are Altered in HIV-Infected Participants With Respect to Neurocognitive Status and Antiretroviral Therapy.

With advances in HIV treatment, people with HIV (PWH) are living longer but experience aging-related comorbidities, including cognitive deficits, at higher rates than the general population. Previous studies have shown alterations in lysosomal proteins in blood from PWH with severe dementia. However, these markers have not been evaluated in PWH with milder neurocognitive impairment.