A5049151623- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- Immune Cell Function and Interaction
- Pneumocystis jirovecii pneumonia detection and treatment
- Pneumonia and Respiratory Infections
- Long-Term Effects of COVID-19
- Cytomegalovirus and herpesvirus research
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- HIV-related health complications and treatments
- COVID-19 and healthcare impacts
- Vaccine Coverage and Hesitancy
- Hepatitis B Virus Studies
- Cervical Cancer and HPV Research
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- COVID-19 epidemiological studies
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Nosocomial Infections in ICU
- COVID-19 and Mental Health
Aarhus University Hospital
2016-2025
Aarhus University
2016-2025
University of Copenhagen
2018-2023
Health Net
2023
University Health Network
2023
The University of Sydney
2018
GTx (United States)
2018
Pharmacologically-induced activation of replication competent proviruses from latency in the presence antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse humans have yielded mixed results. Here, we report proof-of-concept phase Ib/IIa trial where 6 aviremic infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, cellular...
Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection blocking virus-activating host cell TMPRSS2. However, antiviral activity of metabolites and potential viral resistance have not been analyzed. Moreover, in human lung tissue remains be demonstrated.
BackgroundUpon SARS-CoV-2 infection, most individuals develop neutralizing antibodies and T-cell immunity. However, some reportedly remain PCR positive by pharyngeal swabs weeks after recovery. Whether viral RNA in these persistent carriers is contagious stimulates SARS-CoV-2-specific immune responses unknown.MethodsThis cohort study was conducted between April 3rd–July 9th 2020, recruiting COVID-19 recovered that were symptom-free for at least 14 days. We collected serum total Ig, IgA IgM...
Understanding the molecular pathways driving acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments severe COVID-19. Here, we find decreasing number of circulating plasmacytoid dendritic cells (pDCs) in COVID-19 patients early after symptom onset, correlating with disease severity. pDC depletion transient coincides decreased expression type I IFNα systemic cytokines CXCL10 IL-6. Using an vitro stem cell-based human model, further demonstrate...
Objective: We aimed to compare the potential for inducing HIV production and effect on T-cell activation of potent HDAC inhibitors undergoing clinical investigation.Design: In vitro studyMethods: The latently infected cell lines ACH2 U1 were treated with panobinostat, givinostat, belinostat, vorinostat valproic acid. Viral induction was estimated by p24 production. Peripheral blood mononuclear cells from uninfected donors expression markers phenotypes measured using flow cytometry. Finally,...
Treatment with latency reversing agents (LRAs) enhances human immunodeficiency virus type 1 (HIV-1) transcription in vivo but leads to only modest reductions the size of reservoir, possibly due insufficient immune-mediated elimination infected cells. We hypothesized that a single drug molecule—a novel Toll-like receptor 9 (TLR9) agonist, MGN1703—could function as an enhancer innate immunity and LRA vivo. conducted single-arm, open-label study which 15 virologically suppressed HIV-1–infected...
HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However must continued for life, because interruption of ART leads to rapid recrudescence from long-lived latently infected cells. A number approaches are currently being developed 'purge' the reservoir cells order either eliminate completely, or significantly delay time viral after interruption. fundamental question research is how frequently virus reactivates latency, and thus much might need...
ABSTRACT Toll-like receptor (TLR) agonists are potent enhancers of innate antiviral immunity and may also reverse HIV-1 latency. Therefore, TLR have a potential role in the context “shock-and-kill” approach to eradicate HIV-1. Our extensive preclinical evaluation suggests that novel TLR9 agonist, MGN1703, indeed perform both functions an eradication trial. Peripheral blood mononuclear cells (PBMCs) from aviremic HIV-1-infected donors on antiretroviral therapy (ART) were incubated with...
There are limited data on outcomes of moderate to severe coronavirus disease 2019 (COVID-19) among patients treated with remdesivir and dexamethasone in a real-world setting. We sought compare the effectiveness standard care (SOC) alone versus SOC plus dexamethasone.Two population-based nationwide cohorts individuals hospitalized COVID-19 during February through December 2020 were studied. Death within 30 days need mechanical ventilation (MV) compared by inverse probability treatment...
Introduction of vaccines against COVID-19 has provided the most promising chance to control world-wide pandemic. However, adenovirus-vector based Oxford/AstraZeneca [ChAdOx1] (AZ) and Johnson & [Ad26.CoV2.S] have been linked with serious thromboembolic events combined thrombocytopenia, denominated Vaccine-induced Immune Thrombocytopenia Thrombosis (VITT). The pathogenesis VITT remain incompletely understood; especially initial that trigger platelet activation, factor (PF)4 release,...
This was an exploratory, single-arm clinical trial that tested the immune enhancement effects of 24-weeks Toll-like receptor 9 (TLR9) agonist (MGN1703; Lefitolimod; 60 mg × 2 weekly) therapy.We enrolled HIV-1-infected individuals on suppressive combination antiretroviral therapy. Safety assessed throughout study. The primary outcome reduction in total CD4 T-cell viral DNA levels. Secondary outcomes included safety, detailed immunological and virological analyses, time to rebound (viral load...
SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk breakthrough infection in a fully vaccinated cohort. anti-spike IgG levels were measured before first vaccination at day 21-28, 90 180, as well after booster vaccination. Breakthrough infections captured through Danish National Microbiology database. incidence rate ratio (IRR) for time-updated was determined using Poisson regression. Among...
The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of infections and aid search evaluation new treatment modalities vaccines, comprehensive characterization adaptive immune responses towards is needed.
Although persistent symptoms after coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on diversity and duration of needed.Patients aged ≥18 years with positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome 2 who were hospitalized at Department Infectious Diseases, Aarhus University Hospital, Denmark, in period from March 11 May 15 offered follow-up hospitalization. On admission, comprehensive symptom medical history...
BackgroundThe administration of broadly neutralising anti-HIV-1 antibodies before latency reversal could facilitate elimination HIV-1-infected CD4 T cells. We tested this concept by combining the antibody 3BNC117 in combination with latency-reversing agent romidepsin people HIV-1 who were taking suppressive antiretroviral therapy (ART).MethodsWe did a randomised, open-label, phase 2A trial at three university hospital centres Denmark, Germany, and USA. Eligible participants virologically...
Abstract In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally individuals with HIV-1 starting antiviral therapy (ART) or without adjunctive bNAb 3BNC117 treatment. Using activation-induced marker (AIM) assay and interferon-γ release, observe that frequencies of Pol-...
To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies.Adults without history SARS-CoV-2 infection from Danish population scheduled for vaccination were enrolled in this parallel group, phase 4 study. Spike IgG Spike-ACE2-receptor-blocking antibodies measured at days 0, 21, 90, 180. Vaccine was categorized according to levels day 90 after first vaccination. Nondurable response defined as day-90...