Publications by authors named "Joseph J Eron"
T cells are involved in protective immunity against numerous viral infections. Data regarding functional roles of human T cells in SARS-CoV-2 (SARS2) viral clearance in primary COVID-19 are limited. To address this knowledge gap, we assessed samples for associations between SARS2 upper respiratory tract viral RNA levels and early virus-specific adaptive immune responses for 95 unvaccinated clinical trial participants with acute primary COVID-19 aged 18-86 years old, approximately half of whom were considered at high risk for progression to severe COVID-19.
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- - The text emphasizes that new antiretroviral drugs and formulations are continuously being developed for HIV prevention and treatment, highlighting the importance of updated strategies to manage the virus effectively.
- - A panel of expert physician scientists has compiled updated recommendations for 2024 based on extensive literature reviews and data from scientific conferences, focusing on treatment protocols tailored to specific patient needs.
- - Current recommendations advocate for antiretroviral therapy for all individuals with HIV, primarily using integrase strand transfer inhibitors, while also offering alternatives for those with unique circumstances, and suggesting both oral and injectable options for HIV prevention.
Background: Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited.
Methods: This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI.
We explored viral and symptom rebound after COVID-19 amubarvimab/romlusevimab monoclonal antibody therapy vs placebo in the randomized ACTIV-2/A5401 trial. Participants underwent nasal SARS-CoV-2 PCR at study days 3, 7, 14, and 28. Viral rebound was defined as RNA ≥3 and ≥0.
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- Monkeypox (mpox) has become more common and serious for people with HIV since 2022, with researchers looking into why some get sick and how others can protect themselves.
- From a study of nearly 20,000 people living with HIV, 413 cases of mpox were found, with specific groups being more at risk, like younger people and those not on treatment for HIV.
- The monkeypox vaccine was shown to be very effective, especially for people with a healthy immune system, but a lot of Black individuals with HIV were not getting vaccinated as often as others.
Introduction: Treatment for people with HIV-1 and end-stage kidney disease (ESKD) on haemodialysis (HD) has previously required complex dose-adjusted regimens, with limited data on the use of a single-tablet regimen in this population. Our aim was to assess the efficacy and safety of once-daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and to evaluate the pharmacokinetics of bictegravir (BIC) in adults with HIV-1 and ESKD on HD.
Methods: We performed an open-label extension (OLE) of an open-label, multicentre, single-group phase 3b study (NCT02600819) of adults with ESKD on HD and HIV-1 with virological suppression.
Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) extends dosing intervals from daily to every 8 weeks. Equitable implementation requires anticipating and addressing barriers to use. We described LAI-CAB/RPV eligibility and initiation among persons with HIV (PWH) receiving care at a Southeastern US academic medical center.
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- A study investigated whether the monoclonal antibodies amubarvimab/romlusevimab could lower the risk of Long COVID in non-hospitalized high-risk adults treated soon after COVID-19 symptoms began.
- Results showed that while this treatment significantly reduced hospitalizations and deaths (4% vs. 13% in the placebo group), it did not decrease the incidence of Long COVID symptoms, with 16% of treated participants reporting Long COVID compared to 14% in the placebo group.
- The conclusion is that although amubarvimab/romlusevimab is effective for immediate COVID-19 outcomes, additional strategies are necessary to prevent Long COVID.
Background: Anti-SARS-CoV-2 monoclonal antibodies (mAbs) have played a key role as an anti-viral against SARS-CoV-2, but there is a potential for resistance to develop. The interplay between host antibody responses and the development of monoclonal antibody (mAb) resistance is a critical area of investigation. In this study, we assessed host neutralizing antibody (nAb) responses against both ancestral virus and those with treatment-emergent E484K bamlanivimab resistance mutations.
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- The study evaluates two different antibody detection assays (MSD and Bio-Plex Pro) for their effectiveness in measuring antibodies against SARS-CoV-2, focusing on various antibody types (IgG, IgM, IgA) and antigens (RBD, N).
- Results showed high concordance (90.5% for anti-RBD IgG and 87% for anti-N IgG) in determining sample status as positive or negative across the two assays, indicating they can reliably assess immune responses.
- The research also found that participants treated with the monoclonal antibody bamlanivimab showed reduced IgG responses compared to those given a placebo, suggesting the treatment affects immune response
Background And Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort.
Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020.
Article Synopsis
- Therapeutic monoclonal antibodies (mAbs), specifically bamlanivimab targeting the SARS-CoV-2 spike protein, have been shown to alter the memory B cell (MBC) responses in individuals already infected with the virus.
- The treatment skewed MBCs to favor non-receptor binding domain (RBD) epitopes, resulting in a weaker affinity for RBD memory B cells compared to those who received a placebo.
- Even after mRNA COVID-19 vaccination, these changes persisted, indicating that mAb treatment can have lasting effects on immune memory and how the immune system recognizes specific viral epitopes.
Background: We evaluated the fully human polyclonal antibody product SAB-185 in a phase 3 trial for COVID-19.
Methods: Nonhospitalized high-risk adults within 7 days of symptom onset were randomized 1:1 to open-label SAB-185 3840 units/kg or casirivimab/imdevimab 1200 mg. Noninferiority comparison was undertaken for pre-Omicron population (casirivimab/imdevimab expected to be fully active) and superiority comparison for the Omicron population (casirivimab/imdevimab not expected to be active).
Background: Reliable biomarkers of coronavirus disease 2019 (COVID-19) outcomes are critically needed. We evaluated associations of spike antibody (Ab) and plasma nucleocapsid antigen (N Ag) with clinical outcomes in nonhospitalized persons with mild-to-moderate COVID-19.
Methods: Participants were nonhospitalized adults with mild-to-moderate COVID-19 enrolled in ACTIV-2 between January and July 2021 and randomized to placebo.
Background: Persistence of HIV-1 in reservoirs necessitates life-long antiretroviral therapy (ART). There are conflicting data using genetic analysis on whether persistence includes an actively replicating reservoir with strong evidence arguing against replication.
Methods: We investigated the possibility of ongoing viral evolution during suppressive therapy by comparing near full-length viral genomic sequences using phylogenetic analysis of viral RNA in plasma before therapy initiation early after infection and from virus induced to grow from the latent reservoir after a period of suppressive ART.
Article Synopsis
- Outpatient treatment of COVID-19 using subcutaneous monoclonal antibodies (mAbs) could simplify logistics compared to intravenous delivery.
- In a clinical trial with 211 participants, the BMS mAbs did not show significant benefits in symptom improvement or viral load reduction compared to placebo, despite being safe with fewer severe adverse events reported.
- The results suggest that subcutaneous administration of BMS mAbs may not be effective for low-risk COVID-19 patients, potentially due to how the body absorbs mAbs through this method.
Article Synopsis
- Monoclonal antibodies are an important treatment for COVID-19, and a study compared the effects of single vs. dual mAb treatments, specifically amubarvimab and romlusevimab.
- The study found that dual-active mAbs resulted in a quicker reduction of viral load in patients, though hospitalizations and death rates were similar between the two treatment types.
- Additionally, dual-active therapy showed a lower incidence of resistance mutations compared to single-active treatment.
Article Synopsis
- Emergency use authorization allowed several monoclonal antibody (mAb) therapies to treat mild-to-moderate COVID-19 in high-risk patients, targeting the virus's spike protein to prevent infection.
- While mAb therapy can reduce viral loads and hospitalization rates, cases of viral resistance have led to significant viral rebounds in some patients.
- Researchers developed models to explain these rebounds, suggesting that replenishing target cells is necessary, and variations in immune response may determine who experiences these significant rebounds.
HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear.
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- - The study examined the effects of starting antiretroviral therapy (ART) during acute or early HIV infection on the viral reservoir and immune responses in participants from various regions.
- - Results showed that starting ART earlier resulted in lower levels of HIV DNA in the blood, particularly for those who began treatment in the very early stages of infection, but it did not fully eliminate the presence of HIV-infected cells.
- - Despite achieving viral suppression at 48 weeks, the study found no strong correlation between HIV DNA levels and the strength of HIV-specific T cell immune responses, suggesting that early treatment may reduce, but not completely prevent, viral rebound after stopping ART.
Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4 T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir.
Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4 counts ≥350 cells/μL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE).
Article Synopsis
- The study investigated how diverse strains of HIV relate to their vulnerability to broadly neutralizing antibodies (bNAbs) in 89 individuals starting ART early in HIV-1 infection.
- It found similar levels of HIV-1 diversity and predicted bNAb susceptibility at the start of treatment, suggesting stability in viral diversity during ART.
- The results indicate that the initial viral strain may help identify individuals who could respond well to bNAb treatments in clinical trials.
Background: In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19.
Objectives: To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system.
Methods: We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022.
Background: The histone deacetylase inhibitor vorinostat (VOR) can reverse human immunodeficiency virus type 1 (HIV-1) latency in vivo and allow T cells to clear infected cells in vitro. HIV-specific T cells (HXTCs) can be expanded ex vivo and have been safely administered to people with HIV (PWH) on antiretroviral therapy.
Methods: Six PWH received infusions of 2 × 107 HXTCs/m² with VOR 400 mg, and 3 PWH received infusions of 10 × 107 HXTCs/m² with VOR.
Article Synopsis
- A study on people with HIV (PWH) assessed how different subgroups experience internalized HIV stigma (IHS) using a four-item survey between February 2016 and November 2022, involving over 12,000 participants.
- Results showed that younger individuals, cisgender women, and those living in specific regions reported higher IHS scores, while Black/African American and Latine participants had lower scores compared to their White counterparts.
- The study emphasizes the widespread nature of IHS among PWH and the importance of tailored interventions and routine screenings to address and reduce stigma within different subgroups.