Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1385&sort=keywords
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=keywords", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1442&sort=keywords", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1386&sort=keywords", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1384&sort=keywords" }, "data": [ { "type": "Grant", "id": "6898", "attributes": { "award_id": "1R43HL160312-01A1", "title": "Novel Orally Available CBP/Beta-Catenin Antagonists to Treat Idiopathic Pulmonary Fibrosis", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 22688, "first_name": "Louis J.", "last_name": "Vuga", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-03-05", "end_date": "2023-02-28", "award_amount": 334008, "principal_investigator": { "id": 22729, "first_name": "Omar", "last_name": "Haffar", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 1528, "ror": "", "name": "3+2 PHARMA, LLC", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1528, "ror": "", "name": "3+2 PHARMA, LLC", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "PROJECT SUMMARY/ABSRACT Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive fibrosing interstitial pneumonia characterized by the formation of scar tissue within the lungs in the absence of any known cause. IPF is a devastating disease with a poor prognosis and a median survival time of 2–4 years. The natural history of IPF is heterogeneous and most patients follow a slowly declining clinical course after diagnosis. However, episodes of acute respiratory worsening, are experienced by a significant minority. Currently there are two drugs approved by the FDA for the treatment of IPF, Boehringer Ingelheim's nintedanib and Roche's pirfenidone. Both drugs only modestly slow development of scar tissue in lungs of IPF patients. However, neither can reverse nor even halt disease progression, as they merely serve to slow the decline in patients' lung function. Therefore, there is a great unmet need to develop new therapeutics for IPF patients that can minimally stabilize and potentially reverse the course of the disease. Additionally, many patients with severe COVID-19 infections with comorbidities, subsequently develop pulmonary fibrotic disease1 and activation of Wnt/β-catenin signaling is associated with ventilator- induced pulmonary fibrosis2. IPF is a disease caused by injury to alveolar epithelial cells (AECs) with subsequent aberrant repair and over activation of mesenchymal cells with the formation of fibroblastic and myofibroblastic foci. It is well documented that Wnt/β-catenin signaling is important in the survival, migration, and proliferation of AECs and activated Wnt/β-catenin signaling in fibroblasts increases migration, proliferation, and extracellular matrix (e.g. collagen) production. However, the role of β-catenin signaling in fibrosis appears to follow a “Goldilocks” model, where too little β-catenin signaling in AT2 cells promotes epithelial cell death thereby exacerbating lung injury and fibrosis, whereas aberrantly high β-catenin signaling enhances the fibrotic phenotype via fibroproliferation, migration, and activation. Furthermore, the fate of “good” versus “bad” β-catenin signaling is dictated by β-catenin’s differential coactivator usage (Fig. 1)3. Therefore, safe modulation of Wnt/β-catenin signaling is a very appealing therapeutic strategy to treat pulmonary fibrosis. To date, there are no such molecularly targeted drugs that modulate Wnt/β-catenin signaling and differential Kat3 (i.e. CBP and p300) coactivator usage, for IPF in clinical trials. The proposed research plan outlines the development of a potent and highly specific small molecule, orally available, CBP/β-catenin antagonist, [3+2]-517. This lead compound and drug candidate demonstrates promising activity in the bleomycin induced mouse model of fibrosis when dosed orally. The proposed research centers on in vivo evaluation of [3+2]-517 to reverse late stage pulmonary fibrosis and to develop a highly efficient and convergent scale up synthesis for [3+2]-517 to serve as the basis for GLP/GMP production of the API for IND-enabling toxicology studies and clinical batch for the human phase 1 trial. “GOOD” ß-cat signaling (p300/ß-cat) “Bad” ß-cat signaling (CBP/ß-cat) “Bad” ß-cat signaling (CBP/ß-cat) Fig. 1. Model for ß-catenin signaling during lung injury, repair and fibrosis. Modified figure from Cara J. Gottardi and Melanie Königshoff; Am J Respir Crit Care Med 2013 187566-568.", "keywords": [ "AGTR2 gene", "Acute", "Adenovirus Vector", "Affect", "Animal Model", "Bleomycin", "Caring", "Cell Death", "Cells", "Chronic", "Cicatrix", "Cirrhosis", "Clinic", "Clinical", "Clinical Research", "Clinical Trials", "Collagen", "Continuous Intravenous Infusion", "Development", "Diagnosis", "Disease", "Disease Progression", "Dose", "EP300 gene", "Epithelial Cells", "Extracellular Matrix", "FDA approved", "Felis catus", "Fibroblasts", "Fibrosis", "Formulation", "Gene Expression", "Generations", "Grant", "Hepatitis C virus", "Human", "Immune", "In Vitro", "Injury", "Interstitial Pneumonia", "Investigation", "Japan", "Kidney", "Lead", "Liver", "Liver Fibrosis", "Lung", "Mesenchymal", "Minority", "Modeling", "Mus", "Natural History", "New Agents", "Oral", "Patients", "Pharmaceutical Preparations", "Phase I Clinical Trials", "Phenotype", "Pirfenidone", "Population", "Preclinical Testing", "Production", "Prognosis", "Pulmonary Fibrosis", "Research", "Role", "SARS-CoV-2 infection", "Safety", "Signal Transduction", "Structure of parenchyma of lung", "Technology", "Therapeutic", "Time", "Tissues", "Toxicology", "Transforming Growth Factor beta", "Ventilator", "WNT Signaling Pathway", "alveolar epithelium", "analog", "base", "beta catenin", "clinical development", "comorbidity", "design", "drug candidate", "experience", "idiopathic pulmonary fibrosis", "improved", "in vivo evaluation", "indium-bleomycin", "injury and repair", "interstitial", "liver function", "lung injury", "migration", "molecular drug target", "mouse model", "nano-string", "nintedanib", "novel", "novel therapeutics", "phase I trial", "potential biomarker", "pre-clinical", "preclinical study", "pulmonary function", "repaired", "respiratory", "scale up", "severe COVID-19", "small molecule" ], "approved": true } }, { "type": "Grant", "id": "6946", "attributes": { "award_id": "3P01AI073693-11A1S1", "title": "Effect of Covid-19 engagement of ACE2 on brain health and pathology", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 7372, "first_name": "David R.", "last_name": "Johnson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-12-08", "end_date": "2022-06-30", "award_amount": 196504, "principal_investigator": { "id": 9461, "first_name": "Betty", "last_name": "Diamond", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 1019, "ror": "https://ror.org/05dnene97", "name": "Feinstein Institute for Medical Research", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 1019, "ror": "https://ror.org/05dnene97", "name": "Feinstein Institute for Medical Research", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "There are mechanisms in the brain that regulate interactions between neurons and microglial cells and promote homeostasis. These are perturbed in several diseases including neuropsychiatric lupus, NPSLE, studied in this PPG, and following sepsis. Many conditions of neuroinflammation are characterized by microglial activation, and, as a consequence of this activation, by neuronal dendritic pruning and an impaired blood brain barrier. Interestingly, a pathway regulating homeostasis in the brain and dysregulated by neuroinflammation is the renin-angiotensin system. Angiotensin II is generated by angiotensin converting enzyme, ACE, and binds to a receptor AT-1 to enhance inflammation. ACE inhibitors or angiotensin receptor blockers, ARBs, can improve neuroinflammation by either decreasing production or neutralizing angiotensin II. In this pathway, ACE2, a membrane-bound protease, also functions to destroy angiotensin and to generate a small angiotensin peptide, ang1-7, that is anti-inflammatory. ACE2 is the cellular receptor for Covid-19, and binds the viral spike protein, S, more specifically, the receptor binding domain, RBD. This study will examine the binding of S and RBD to normal mouse brain and to mouse brain mimicking NPSLE or sepsis survival. We will further study whether engagement by S or RBD alters the functional state of neurons, microglia and brain endothelial cells. Finally, we ask whether the use of ACE inhibitors or ARBs alters S or RBD binding, and whether S or RBD impair the efficacy of these medications in halting or reversing the neurodegenerative process in NPSLE and in sepsis survivors. This study cannot be performed in humans, but it has important translational implications.", "keywords": [ "AGTR2 gene", "Address", "Affect", "Alzheimer&apos", "s Disease", "Angiotensin I", "Angiotensin II", "Angiotensin Receptor", "Angiotensin-Converting Enzyme Inhibitors", "Angiotensins", "Anti-Inflammatory Agents", "Antibodies", "Antihypertensive Agents", "Behavior", "Binding", "Blood - brain barrier anatomy", "Brain", "Brain Pathology", "COVID-19", "Cardiac", "Cells", "Chronic", "Cleaved cell", "Cognition", "Coronavirus", "Data", "Dendrites", "Disease", "Drug usage", "Effectiveness", "Enzymes", "Epithelial Cells", "Exhibits", "G-Protein-Coupled Receptors", "GTP-Binding Protein alpha Subunits Gs", "Genetic Transcription", "Goals", "Homeostasis", "Human", "Impairment", "Individual", "Inflammation", "Inflammatory Response", "Interferons", "Mediating", "Membrane", "Microglia", "Modeling", "Mus", "Nerve Degeneration", "Neuraxis", "Neurons", "Neuropsychiatric Systemic Lupus Erythematosus", "Pathologic", "Pathology", "Pathway interactions", "Penetration", "Peptide Hydrolases", "Peptides", "Peptidyl-Dipeptidase A", "Peripheral Nervous System", "Pharmaceutical Preparations", "Positron-Emission Tomography", "Process", "Production", "Proteins", "Renal Tissue", "Renin-Angiotensin System", "Role", "Sepsis", "Survivors", "System", "TNF gene", "Therapeutic Effect", "Tissues", "Viral", "Virus", "arm", "base", "brain cell", "brain endothelial cell", "brain health", "cytokine", "enzyme pathway", "human disease", "human subject", "immune activation", "improved", "in vivo", "interest", "mouse model", "neuroinflammation", "prevent", "programs", "receptor", "receptor binding", "uptake" ], "approved": true } }, { "type": "Grant", "id": "9069", "attributes": { "award_id": "3UM1AI069419-14S1", "title": "WCM-Rutgers NJMS CTU Supplement for COVID Testing", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 24868, "first_name": "Teri L.", "last_name": "Greenfield", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-16", "end_date": "2021-11-30", "award_amount": 300000, "principal_investigator": { "id": 24869, "first_name": "ROY M.", "last_name": "GULICK", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 825, "ror": "", "name": "WEILL MEDICAL COLL OF CORNELL UNIV", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 825, "ror": "", "name": "WEILL MEDICAL COLL OF CORNELL UNIV", "address": "", "city": "", "state": "NY", "zip": "", "country": "United States", "approved": true }, "abstract": "The Rutgers New Jersey Medical School (NJMS) Clinical Research Site (CRS) 31786 is requesting $300,000 in funding to help support Severe Acute Respiratory Distress Syndrome Coronavirus-2 (SARS-CoV-2) testing. The CRS is part of the Weill Cornell-Rutgers NJMS Clinical Trials Unit and has been a site for two Division of AIDS (DAIDS) funded clinical trials networks: AIDS Clinical Trials Group (ACTG) and HIV Prevention Trials Network (HPTN) for fifteen years. The program plans to provide SARS-CoV-2 testing by leveraging its existing relationships with the local community and partnering with the clinical laboratory located at Public Health Research Institute (PHRI), also a Rutgers facility to perform SARS-CoV-2 testing using the Cepheid testing platform. The Cepheid COVID-19 testing platform has been developed at PHRI with Cepheid and is one of the most sensitive tests currently available to detect SARS-Co-V 2 infection. We will provide SARS-CoV-2 testing at the CRS, in an adjacent building and on a mobile van. These testing locations are well-known and easily accessible to the community, healthcare workers and other high-risk groups. We will also attempt to ensure that special populations such as minorities and the LGBTQ community have access to the test. Finally, this will help the CRS further strengthen its relationship with the community and allow the unit to provide an essential service to this hard-hit community. If funded, this project will allow us to rapidly increase the availability of SARS CoV-2 testing and help contribute to the urgent need for additional COVID testing in an underserved community located near the epicenter of the COVID-19 pandemic in the United States.", "keywords": [ "AIDS clinical trial group", "Acquired Immunodeficiency Syndrome", "Address", "Administrative Supplement", "Adult Respiratory Distress Syndrome", "Affect", "Area", "COVID-19", "COVID-19 pandemic", "Clinical", "Clinical Trials", "Clinical Trials Network", "Clinical Trials Unit", "Communities", "Community Healthcare", "Coronavirus", "Enrollment", "Ensure", "Funding", "Future", "HIV prevention trials network", "Health Personnel", "Individual", "Infection", "Laboratories", "Lesbian Gay Bisexual Transgender Queer", "Location", "Minority", "New Jersey", "Research Institute", "Services", "Severe Acute Respiratory Syndrome", "Site", "Testing", "United States", "Work", "clinical research site", "cohort", "coronavirus disease", "high risk population", "infection rate", "interest", "medical schools", "named group", "pandemic disease", "programs", "public health research" ], "approved": true } }, { "type": "Grant", "id": "6232", "attributes": { "award_id": "3U01HL146194-02S3", "title": "UNC MACS/WIHS Combined Cohort Study Clinical Research Site", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Mental Health (NIMH)" ], "program_reference_codes": [], "program_officials": [ { "id": 21107, "first_name": "SEAN FITZGERALD", "last_name": "Altekruse", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2019-04-01", "end_date": "2026-03-31", "award_amount": 4252, "principal_investigator": { "id": 21108, "first_name": "ADAORA A", "last_name": "ADIMORA", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "This application proposes to establish The University of North Carolina at Chapel Hill as a Clinical Research Site (CRS) for the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS-CCS). The proposal represents a collaborative effort between investigators from The UNC Institute for Global Health and Infectious Diseases, Center for AIDS Research, UNC Gillings School of Global Public Health, Lineberger Comprehensive Cancer Center, Eshelman School of Pharmacy, and Cecil G. Sheps Center for Health Services Research. We propose to rapidly establish the UNC MACS/WIHS-CCS CRS, contribute meaningfully to the MACS/WIHS- CCS (CCS) Unified Science Agenda, and undertake ambitious research that encompasses pulmonary, cardiovascular, neurocognitive, and other HIV-related comorbidities; HIV pathogenesis/cure; social epidemiology and health outcomes; behavioral research; and advanced epidemiologic methods. We aim to: (1) Enroll 310 male and female participants who reflect the HIV epidemic in the southeastern US, and re-consent current WIHS enrollees for participation in the CCS; (2) Lead critical components of the CCS Unified Science Agenda; (3) Support all aspects of the CCS Science Agenda at the UNC CRS. By contributing a representative population of men and women, innovative science, and a strong, multidisciplinary cadre of investigators, UNC will enhance the efforts of the CCS, expand the range of questions that can be addressed and, in collaboration with the entire group, improve the health of men and women with or at high risk for HIV infection.", "keywords": [ "AIDS clinical trial group", "Acquired Immunodeficiency Syndrome", "Address", "Affect", "Aging", "American", "Area", "Behavioral Research", "Biological Markers", "Blood", "Cardiovascular Diseases", "Cardiovascular system", "Characteristics", "Chronic", "Chronic Obstructive Airway Disease", "Clinical", "Cohort Studies", "Collaborations", "Communicable Diseases", "Complement", "Comprehensive Cancer Center", "Consent", "Data Analyses", "Disease", "Disease remission", "Enrollment", "Epidemic", "Epidemiologic Methods", "Ethnic Origin", "Female", "Funding", "Geography", "Gills", "Grant", "Guidelines", "HIV", "HIV Infections", "HIV Seropositivity", "HIV prevention trials network", "Health", "Health Policy", "Health Services Research", "Incidence", "Individual", "Infection", "Infrastructure", "Institutes", "Insurance Coverage", "Interruption", "Intervention", "Lead", "Leadership", "Link", "Lung", "Lung diseases", "Malignant Neoplasms", "Malignant neoplasm of lung", "Methods", "Myocardial Infarction", "Nature", "Neighborhoods", "Neurocognitive", "North Carolina", "Outcome", "Participant", "Pathogenesis", "Pharmacy Schools", "Plasma", "Population", "Prevention", "Public Health", "Publications", "Race", "Research", "Research Personnel", "Respiratory Signs and Symptoms", "Respiratory physiology", "Risk", "Risk Factors", "Schools", "Science", "Sex Differences", "Site", "Socioeconomic Status", "Stroke", "Structure", "System", "The Multicenter AIDS Cohort Study", "Tissue Procurements", "Tissues", "Universities", "Viral Load result", "Viral reservoir", "Virus Latency", "Woman", "Women’s Interagency HIV Study", "antiretroviral therapy", "career", "clinical research site", "cohort", "collaboratory", "comorbidity", "design", "effective intervention", "gender difference", "global health", "health disparity", "high risk", "high risk population", "improved", "innovation", "interest", "male", "male health", "men", "mortality", "multidisciplinary", "novel", "programs", "research study", "sex", "social epidemiology" ], "approved": true } }, { "type": "Grant", "id": "6233", "attributes": { "award_id": "3U01HL146194-02S4", "title": "UNC MACS/WIHS Combined Cohort Study Clinical Research Site", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 21109, "first_name": "SEAN FITZGERALD", "last_name": "Altekruse", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2019-04-01", "end_date": "2026-03-31", "award_amount": 259788, "principal_investigator": { "id": 21110, "first_name": "ADAORA A", "last_name": "ADIMORA", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true }, "abstract": "This application proposes to establish The University of North Carolina at Chapel Hill as a Clinical Research Site (CRS) for the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study (MACS/WIHS-CCS). The proposal represents a collaborative effort between investigators from The UNC Institute for Global Health and Infectious Diseases, Center for AIDS Research, UNC Gillings School of Global Public Health, Lineberger Comprehensive Cancer Center, Eshelman School of Pharmacy, and Cecil G. Sheps Center for Health Services Research. We propose to rapidly establish the UNC MACS/WIHS-CCS CRS, contribute meaningfully to the MACS/WIHS- CCS (CCS) Unified Science Agenda, and undertake ambitious research that encompasses pulmonary, cardiovascular, neurocognitive, and other HIV-related comorbidities; HIV pathogenesis/cure; social epidemiology and health outcomes; behavioral research; and advanced epidemiologic methods. We aim to: (1) Enroll 310 male and female participants who reflect the HIV epidemic in the southeastern US, and re-consent current WIHS enrollees for participation in the CCS; (2) Lead critical components of the CCS Unified Science Agenda; (3) Support all aspects of the CCS Science Agenda at the UNC CRS. By contributing a representative population of men and women, innovative science, and a strong, multidisciplinary cadre of investigators, UNC will enhance the efforts of the CCS, expand the range of questions that can be addressed and, in collaboration with the entire group, improve the health of men and women with or at high risk for HIV infection.", "keywords": [ "AIDS clinical trial group", "Acquired Immunodeficiency Syndrome", "Address", "Affect", "Aging", "American", "Area", "Behavioral Research", "Biological Markers", "Blood", "Cardiovascular Diseases", "Cardiovascular system", "Characteristics", "Chronic", "Chronic Obstructive Airway Disease", "Clinical", "Cohort Studies", "Collaborations", "Communicable Diseases", "Complement", "Comprehensive Cancer Center", "Consent", "Data Analyses", "Disease", "Disease remission", "Enrollment", "Epidemic", "Epidemiologic Methods", "Ethnic Origin", "Female", "Funding", "Geography", "Gills", "Grant", "Guidelines", "HIV", "HIV Infections", "HIV Seropositivity", "HIV prevention trials network", "Health", "Health Policy", "Health Services Research", "Incidence", "Individual", "Infection", "Infrastructure", "Institutes", "Insurance Coverage", "Interruption", "Intervention", "Lead", "Leadership", "Link", "Lung", "Lung diseases", "Malignant Neoplasms", "Malignant neoplasm of lung", "Methods", "Myocardial Infarction", "Nature", "Neighborhoods", "Neurocognitive", "North Carolina", "Outcome", "Participant", "Pathogenesis", "Pharmacy Schools", "Plasma", "Population", "Prevention", "Public Health", "Publications", "Race", "Research", "Research Personnel", "Respiratory Signs and Symptoms", "Respiratory physiology", "Risk", "Risk Factors", "Schools", "Science", "Sex Differences", "Site", "Socioeconomic Status", "Stroke", "Structure", "System", "The Multicenter AIDS Cohort Study", "Tissue Procurements", "Tissues", "Universities", "Viral Load result", "Viral reservoir", "Virus Latency", "Woman", "Women’s Interagency HIV Study", "antiretroviral therapy", "career", "clinical research site", "cohort", "collaboratory", "comorbidity", "design", "effective intervention", "gender difference", "global health", "health disparity", "high risk", "high risk population", "improved", "innovation", "interest", "male", "male health", "men", "mortality", "multidisciplinary", "novel", "programs", "research study", "sex", "social epidemiology" ], "approved": true } }, { "type": "Grant", "id": "6951", "attributes": { "award_id": "3U01HL123336-06S3", "title": "REPRIEVE - CCC - Lead Application", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 10288, "first_name": "Patrice", "last_name": "Desvigne-Nickens", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2014-08-08", "end_date": "2023-04-30", "award_amount": 1210912, "principal_investigator": { "id": 10289, "first_name": "Pamela Susan", "last_name": "Douglas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 10290, "first_name": "STEVEN K.", "last_name": "GRINSPOON", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "In response to NOT-HL-20-757, Notice of Special Interest (NOSI): Availability of Administrative Supplements and revision Supplements on Coronavirus Disease 2019 (COVID-19), and PA-18-591 Administrative Supplements for existing NIH Grants and Cooperative Agreements, the enclosed administrative supplement, leveraging parent grant U01 HL123336, is submitted for consideration. Understanding COVID-related CV complications in at-risk populations represents an urgent national priority. Retrospective case series have shown that among patients in the general population hospitalized with COVID-19, approximately 20 to 30% evidence myocardial injury, which is associated with adverse outcomes including cardiac dysfunction, arrythmia, hypercoagulable events, and death. In addition, significant evidence exists for endothelial and vascular dysfunction related to COVID-19, related to membrane uptake via ACE-2 or other mechanisms. People with HIV (PWH) already face increased risk of myocardial infarction and heart failure as compared with the general population. How COVID-19 affects CV morbidity and mortality among PWH remains unknown and preventive/therapeutic strategies have yet to be identified. We propose to leverage the REPRIEVE trial – the largest international randomized trial focused on preventing HIV-associated CV disease – to address critical knowledge gaps regarding SARS-CoV-2 infection and COVID-related CV complications among PWH. Studying 7,700 PWH ages 40-75 across 5 continents, we will focus on three interrelated but independent key topics: epidemiology, host factors, and protective strategies. In this regard, statins have pleiotropic effects and potently reduce vascular inflammation and improve endothelial function, The results of the supplement will provide critical information on HIV and COVID-19, and conversely critical effects of statins to mitigate effects of the SARS-Co-V2 virus on cardiovascular disease and endothelial function, and MACE. These results will be broadly generalizable to the large population of HIV patients simultaneously at risk for COVID-19 and CVD and also to other populations at risk for CVD experiencing COVID infection.", "keywords": [ "AIDS clinical trial group", "Acquired Immunodeficiency Syndrome", "Adverse effects", "Angiography", "Arterial Fatty Streak", "Arteries", "Atherosclerosis", "Authorization documentation", "Biological Factors", "Biological Markers", "Biology", "Blood Tests", "CCL2 gene", "Cardiac", "Cardiopulmonary Resuscitation", "Cardiovascular Diseases", "Cardiovascular system", "Cessation of life", "Characteristics", "Coagulation Process", "Collaborations", "Coronary", "Data", "Data Coordinating Center", "Disease", "Dyslipidemias", "Endothelium", "Enrollment", "Event", "Fibrin fragment D", "Glucose", "Glycosylated hemoglobin A", "Grant", "HIV", "Heart", "Heart Arrest", "Heart Diseases", "Hospitalization", "Image", "Immune", "Immunologic Markers", "Immunologics", "Incidence", "Infection", "Inflammation", "Inflammatory", "Insulin", "LDL Cholesterol Lipoproteins", "Lead", "Lipids", "Liver", "Liver Dysfunction", "Low-Density Lipoproteins", "Malignant Neoplasms", "Mediating", "Medicine", "Morphology", "Muscle", "Myocardial Infarction", "Myositis", "National Heart Lung and Blood Institute", "National Institute of Allergy and Infectious Disease", "Organization and Administration", "Participant", "Particle Size", "Pathway interactions", "Patients", "Peripheral", "Population", "Prevalence", "Prevention strategy", "Primary Prevention", "Property", "Randomized", "Research", "Risk", "Risk Factors", "Safety", "Site", "Smoking", "Stroke", "Study models", "T-Lymphocyte", "Testing", "Thromboplastin", "Time", "United States", "Unstable angina", "Update", "Viral Load result", "Work", "X-Ray Computed Tomography", "antiretroviral therapy", "atherogenesis", "attenuation", "blood glucose regulation", "cardiovascular disorder risk", "cardiovascular risk factor", "clinical research site", "coronary plaque", "follow-up", "heart imaging", "high risk", "immune activation", "immune function", "improved", "indexing", "lipoprotein-associated phospholipase A(2)", "monocyte", "mortality", "novel", "oxidized low density lipoprotein", "prevent", "primary endpoint", "randomized placebo-controlled clinical trial", "response", "treatment strategy", "vascular inflammation", "virology" ], "approved": true } }, { "type": "Grant", "id": "11396", "attributes": { "award_id": "1U24HL164284-01", "title": "2/2 REPRIEVE Extension for Trial Completion", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 10288, "first_name": "Patrice", "last_name": "Desvigne-Nickens", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2023-05-01", "end_date": "2026-04-30", "award_amount": 1243585, "principal_investigator": { "id": 27449, "first_name": "Michael Tse-Yin", "last_name": "Lu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 27450, "first_name": "Heather Jane", "last_name": "Ribaudo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 736, "ror": "https://ror.org/002pd6e78", "name": "Massachusetts General Hospital", "address": "", "city": "", "state": "MA", "zip": "", "country": "United States", "approved": true }, "abstract": "This proposal will support the Data Coordinating Center (DCC) for the Randomized Trial to Prevent Vascular Events in HIV Trial (REPRIEVE) Extension for up to two additional years, with an additional year for study close-out. This additional time is necessary to collect the major adverse cardiovascular events (MACE) required to ensure adequate power to address the primary aim of REPRIEVE, to determine the efficacy of statins as a primary cardiovascular prevention strategy in HIV. Completion of the trial will protect the value of the initial NIH investment and leverage existing REPRIEVE infrastructure, with its data analytical and oversight structures. This DCC proposal is a companion to the REPRIEVE Clinical Coordinating Center (CCC) proposal. REPRIEVE is a multicenter, randomized, placebo controlled, pragmatic trial investigating the efficacy of statins for primary prevention of cardiovascular disease (CVD) events (primary endpoint) in 7,770 persons with HIV (PWH) without known CVD and with low to moderate CVD risk as per the 2013 ACC/AHA Pooled Cohort Equations, (referred to as ASCVD risk). To understand the biology of statin effects, 805 participants were co- enrolled in an embedded mechanistic substudy that will determine the effects of statins on non-calcified plaque volume and high risk plaque morphology using coronary computed tomographic angiography (CTA), as well as on blood biomarkers of vascular inflammation and immune activation after 4 months and two years. Further, in response to the global SARS-CoV-2 pandemic, REPRIEVE will address critical knowledge gaps regarding the epidemiology of SARS-CoV-2 infection and COVID-related CVD complications among PWH, and determine the protective statin effects for COVID disease across the globe. In the proposed extension, the REPRIEVE DCC will continue to provide methodological and logistical support for the collection, quality control, and analysis of data including rigorous, timely, and independent adjudication of potential MACE events. Furthermore, the DCC remains responsible for statistical design and analysis, assistance in protocol development, data management, CTA data acquisition and interpretation, biospecimen analysis, and electronic communications.", "keywords": [ "AIDS clinical trial group", "Address", "Ancillary Study", "Angiography", "Authorization documentation", "Biological Assay", "Biological Markers", "Biology", "Blood", "Blood Vessels", "COVID-19 pandemic", "Cardiovascular Diseases", "Cardiovascular system", "Clinical", "Clinical Data", "Clinical Trials", "Clinical Trials Data Monitoring Committees", "Collaborations", "Collection", "Companions", "Computers", "Coronary artery", "Data", "Data Analyses", "Data Analytics", "Data Collection", "Data Coordinating Center", "Data Reporting", "Disease", "Electronic Mail", "Enrollment", "Ensure", "Epidemiology", "Equation", "Event", "HIV", "Heart Diseases", "Information Dissemination", "Infrastructure", "Investments", "Knowledge", "Laboratories", "Lead", "Leadership", "Letters", "Methodology", "Morphology", "Myocardial Infarction", "National Heart Lung and Blood Institute", "Outcome", "Participant", "Persons", "Placebo Control", "Preparation", "Prevention strategy", "Primary Prevention", "Procedures", "Process", "Publications", "Quality Control", "Randomized", "Reporting", "Research", "Research Design", "Risk", "SARS-CoV-2 infection", "Site", "Statistical Data Interpretation", "Stroke", "Structure", "System", "Time", "Training", "United States National Institutes of Health", "X-Ray Computed Tomography", "adjudication", "archive data", "cardiovascular disorder prevention", "cardiovascular disorder risk", "cohort", "coronary computed tomography angiography", "coronavirus disease", "data acquisition", "data archive", "data exchange", "data management", "data repository", "data sharing", "design", "follow-up", "high risk", "imaging study", "immune activation", "inflammatory marker", "medical specialties", "meetings", "pragmatic trial", "prevent", "primary endpoint", "protocol development", "randomized trial", "response", "stroke event", "tool", "trial design", "vascular inflammation" ], "approved": true } }, { "type": "Grant", "id": "9057", "attributes": { "award_id": "3UM1AI068636-15S1", "title": "CoVPN 3502 / ACTIV-2/A5401", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 21580, "first_name": "Akinlolu O", "last_name": "Ojumu", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-24", "end_date": "2022-11-30", "award_amount": 19807516, "principal_investigator": { "id": 21581, "first_name": "Judith S.", "last_name": "Currier", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 21582, "first_name": "Joseph J", "last_name": "Eron", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 817, "ror": "", "name": "UNIV OF NORTH CAROLINA CHAPEL HILL", "address": "", "city": "", "state": "NC", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected with SARS-CoV-2 (CoVPN 3502) Transmission of SARS-CoV-2 occurs primarily through person-to-person contact and respiratory droplet transmission (Lai,2020). Household contacts of a person infected with SARS-CoV-2 are at a high risk for acquiring infection, with transmission rates ranging from approximately 10% to 15%. The majority of individuals who acquire infection from household contacts develop symptoms of COVID-19 (Burke,2020) (Jing, 2020), (Bi,2020) (Li,2020b). Prophylaxis is urgently needed to reduce transmission rates and/or reduce the occurrence of symptomatic disease. Ideally, prophylaxis would need to be given as soon as possible after a known exposure, as the duration of time between symptomatic infection in the source individual and the development of symptoms in newly infected individual is thought to be approximately 5 days, with a possible range of 2 to14 days(Lauer,2020) (Li,2020a). Animal models suggest that SARS-CoV-2 RT-PCR in nasopharyngeal (NP) samples become positive within a few days after infection (Rockx,2020). An ideal agent for prophylaxis should be fast acting and highly effective and should protect against multiple viral variants. A monoclonal antibody (mAb) combination therapy, with two different monoclonal antibodies that bind distinct regions of the portion of the SARS-CoV-2 spike(S) protein that bind to and facilitate entry into host cells, has been developed in order to achieve these goals. A mAb combination against SARS-CoV-2 for post-exposure prophylaxis that can either prevent the development of disease or reduce viral acquisition or shedding could be key to reducing transmission of the virus and limiting symptoms and adverse outcomes following infection. Given the speed at which this outbreak has spread and how it has impacted almost every community globally, there is an urgent need to develop safe and efficacious interventions to slow the spread of the SARS-CoV-2 virus and decrease adverse outcomes associated with symptomatic disease. This study is designed to assess the efficacy and safety of co-administered REGN10933+REGN10987 combination therapy (“REGN10933+REGN10987”) to reduce the proportion of SARS-CoV-2 infections and prevent the development of COVID-19 disease (symptomatic SARS-CoV2 infection), after household exposure to individuals with SARS-CoV-2 infection. ACTIV-2/A5401: Adaptive Platform Treatment Trial for Outpatients with COVID-19 (Adapt Out COVID) – Brii Biosciences Agent Adapt Out COVID is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19. It begins with a phase II evaluation, followed by a transition into a larger phase III evaluation for promising agents. This supplement represents activity for the Brii Biosciences Agent. The trial is a randomized, blinded, controlled adaptive platform that allows agents to be added and dropped during the course of the study for efficient testing of new agents against placebo within the same trial infrastructure. When two or more new agents are being tested concurrently, the same placebo will be used, if feasible. The primary outcome measures in the phase II evaluation will be duration of symptoms, similar to the outcome used for outpatient influenza studies, loss of detection of SARS-CoV-2 RNA by nasopharyngeal (NP) swab, and safety. Determination of whether a phase II agent will continue to be evaluated in phase III will be made after the last participant randomized to that agent or placebo group completes their day 28 phase II visit. If continued, data collected from participants enrolled in phase II will be included in the phase III evaluation. The phase III evaluation is a continuation of the phase II trial for agents that meet study-defined criteria for further evaluation and for which sufficient investigational agent is available. An agent may also enter directly into phase III evaluation based on Trial Oversight Committee (TOC) assessments. The fully powered phase III trial will evaluate the efficacy of each selected investigational agent compared to placebo to prevent hospitalization and death in non-hospitalized adults with COVID-19. The protocol will be amended when information becomes available from within or outside of the trial indicating that further randomization to a placebo is inappropriate.", "keywords": [ "AIDS clinical trial group", "AIDS/HIV problem", "Address", "Affect", "Aging", "Anti-Retroviral Agents", "Antiviral Agents", "Area", "Behavioral", "Biological Markers", "Blood", "California", "Cardiovascular system", "Clinical", "Clinical Research", "Clinical Trials", "Collaborations", "Communication", "Conduct Clinical Trials", "Development", "Disease", "Disease remission", "Drug resistance in tuberculosis", "Epidemic", "Evaluation", "Funding", "Goals", "HIV", "HIV Infections", "HIV/TB", "Health", "Hepatitis B", "Hepatitis B Virus", "Immune", "Immunologics", "Industry Collaboration", "Infection", "Infrastructure", "International", "Intervention", "Knowledge", "Laboratories", "Leadership", "Los Angeles", "Maintenance", "Mental Health", "Metabolic", "Morbidity - disease rate", "Multidrug-Resistant Tuberculosis", "Neurologic", "Obesity", "Occupational activity of managing finances", "Phase", "Population", "Prevention", "Prevention and Treatment of Opportunistic Infection", "Protocols documentation", "Publishing", "Regimen", "Research", "Research Personnel", "Resources", "Risk", "Science", "Specimen", "Structure", "System", "Testing", "Therapeutic", "Therapeutic Intervention", "Tissues", "Training", "Tuberculosis", "Universities", "Virus Diseases", "active method", "acute infection", "antiretroviral therapy", "burden of illness", "chronic infection", "collaboratory", "community engagement", "community involvement", "comorbidity", "comparative efficacy", "data management", "design", "drug-sensitive", "efficacy trial", "improved", "innovation", "mortality", "multidisciplinary", "neutralizing antibody", "novel", "operation", "prevent", "protocol development", "social", "statistics", "therapeutic vaccine", "treatment guidelines", "virology" ], "approved": true } }, { "type": "Grant", "id": "7644", "attributes": { "award_id": "3UM1AI106701-07S1", "title": "A5401 COVID Supplement", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 21127, "first_name": "Daniella", "last_name": "Livnat", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-07-09", "end_date": "2021-11-30", "award_amount": 3770048, "principal_investigator": { "id": 21126, "first_name": "Grace M", "last_name": "Aldrovandi", "orcid": null, "emails": "[email protected]", "private_emails": null, "keywords": "[]", "approved": true, "websites": "[]", "desired_collaboration": "", "comments": "", "affiliations": [ { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 818, "ror": "", "name": "UNIVERSITY OF CALIFORNIA LOS ANGELES", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "The AIDS Clinical Trials Group (ACTG) has been selected to lead a Master Adaptive protocol under the Accelerating COVID-19 Therapeutic Interventions and Vaccine (ACTIV) Operation Warp Speed. This trial (ACTG 5401 or ACTIV-2) will evaluate multiple monoclonal antibodies and other small molecules for outpatient COVID treatment. The Laboratory Center will expand its efforts to include support for COVID-19 clinical trials.", "keywords": [ "AIDS clinical trial group", "AIDS/HIV problem", "Address", "Biological Assay", "Biological Markers", "COVID-19", "Clinical", "Clinical Research", "Clinical Trials", "Collaborations", "DNA Repository", "Evaluation", "Genomics", "HIV", "Health", "Immunology", "International", "Knowledge", "Laboratories", "Laboratory Research", "Lead", "Leadership", "Measures", "Monoclonal Antibodies", "Outpatients", "Pathogenesis", "Patients", "Pharmacology", "Procedures", "Protocols documentation", "Research", "Research Personnel", "Research Priority", "Research Support", "Safety", "Scientific Advances and Accomplishments", "Severe Acute Respiratory Syndrome", "Site", "Specimen", "Speed", "Standardization", "Testing", "Therapeutic", "Therapeutic Intervention", "Total Quality Management", "Training Programs", "United States National Institutes of Health", "base", "coronavirus disease", "data management", "human DNA", "improved", "innovation", "laboratory experience", "novel", "operation", "programs", "small molecule", "therapeutic vaccine", "treatment guidelines" ], "approved": true } }, { "type": "Grant", "id": "14663", "attributes": { "award_id": "1I01CX002698-01", "title": "Leveraging Jak 1/2 Inhibition with Baricitinib Towards HIV Cure in the Veteran Population", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [], "program_reference_codes": [], "program_officials": [], "start_date": "2024-04-01", "end_date": "2027-03-31", "award_amount": null, "principal_investigator": { "id": 31360, "first_name": "Christina", "last_name": "Gavegnano", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 1477, "ror": "https://ror.org/05eq41471", "name": "Veterans Health Administration", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "A major barrier to HIV eradication is maintenance of latently infected cells in people living with HIV (PWH). The Veteran population of PWH is nearly 2.5-fold greater versus non-Veteran individuals living in the United States, underscoring a major unmet need within the United States Veteran's population for safe, specific agents that can cure HIV and prevent or reverse associated co-morbidities. Chronic inflammation despite suppressive ART drives HIV persistence and co-morbidities, including cardiovascular disease, frailty, diabetes, and HIV- associated neurocognitive dysfunction (HAND). The Janus Kinase Signal Transducer and Activator of Signal Transduction (Jak-STAT) pathway is a major mechanism of elevated immune dysregulation, even during viral suppression. In viremic individuals, elevated pSTATs including pSTAT5 are associated with increased reservoir size, viral loads, and decreased CD4+ T cell counts, underscoring the direct link between the Jak-STAT pathway and the HIV-1 reservoir. Our team (Vincent Marconi (VAMC) William Tyor (VAMC) and Christina Gavegnano) has extensively studied the class of Jak 1/2 inhibitors (indication HIV-1), including a first-generation Jak 1/2 inhibitor ruxolitinib, and demonstrated in a recently completed multi-site Phase 2a ACTG-sponsored study (A5336;n=60) that ruxolitinib is safe, well-tolerated, and reduces key markers of immune activation associated with HIV-1 persistence (HLA-DR/CD38, sCD14, and cellular lifespan marker bcl-2). We also showed a reduction in the HIV-1 reservoir in individuals with higher baseline frequency of integrated HIV-1 DNA, demonstrating proof- of-concept that Jak 1/2 inhibition can reduce the reservoir in a clinical setting. Furthermore, we observed that ruxolitinib, in an in vitro model of HIV-1-infection in total memory CD4+ T cells, pushes differentiation of central memory cells (TCM) to a shorter lived phenotype (effector memory T cells-TEM), which could also induce HIV- 1 reservoir decay. Baricitinib is a second-generation Jak 1/2 inhibitor (FDA approved for rheumatoid arthritis and COVID-19), presenting a markedly improved safety profile versus ruxolitinib including approval for chronic long- term use (including children), once daily dosing and renal clearance (making drug-drug interactions with hepatically cleared agents unlikely; critical for add-on to ART). We have shown that baricitinib significantly reduces the HIV-1 reservoir in primary T cells and reverses HIV-1 persistence markers and inflammation (murine model). We also demonstrated that baricitinib confers substantial improvement of CD4/CD8 HIV-specific effector function, boosting natural immune function that may i) enhance reservoir decline and ii) block or prevent inflammatory driven co-morbidities in PWH. However, how baricitinib can confer reservoir reduction in ex vivo patient samples, and in a dynamic in vivo (murine) model of systemic infection, remains unclear. We will define the multi-functional action of baricitinib, a Jak ½ inhibitor developed by our team for treatment of viral infections including HIV and COVID-19, towards control HIV reservoirs and persistence. This will be done by leveraging our now-enrolling Phase2a study for baricitinib towards reduction of HIV-1 reservoir in the CNS (NCT05452564) across peripheral blood and cerebral spinal fluid samples from the study, and existing VA cohorts from Dr. Vincent Marconi (VA, Emory). Additional mechanisms will be bolstered by collaboration with Dr. William Tyor (VA and Emory) using the humanized murine model of HIV-1 infection. Data will streamline translation to additional human studies in the Veteran PWH population, for comorbidities and eventual HIV cure.", "keywords": [ "AIDS clinical trial group", "Antiinflammatory Effect", "BCL2 gene", "CD4 Positive T Lymphocytes", "CD8B1 gene", "COVID-19", "Cardiovascular Diseases", "Cell Count", "Cells", "Cerebrospinal Fluid", "Child", "Chronic", "Clinical", "Collaborations", "DNA", "Data", "Diabetes Mellitus", "Dose", "Drug Interactions", "Enrollment", "Epigenetic Process", "FDA approved", "Frequencies", "Functional disorder", "Generations", "HIV", "HIV-1", "HLA-DR Antigens", "Hepatic", "Human", "Immune", "Immunologic Markers", "In Vitro", "Individual", "Infection", "Inflammation", "Inflammatory", "Interruption", "Investigation", "Janus kinase", "Link", "Longevity", "Maintenance", "Measures", "Memory", "Modeling", "Modification", "Mus", "Myelogenous", "Neurocognitive", "Patients", "Peripheral", "Persons", "Pharmaceutical Preparations", "Phase", "Phenotype", "Population", "Prevention", "Renal clearance function", "Research Personnel", "Rheumatoid Arthritis", "Safety", "Sampling", "Sampling Studies", "Sentinel", "Signal Transduction", "Signal Transduction Pathway", "Site", "Systemic infection", "T memory cell", "T-Lymphocyte", "Testing", "Therapeutic Agents", "Transducers", "Translations", "United States", "Veterans", "Viral", "Viral Load result", "Virus Diseases", "antiretroviral therapy", "behavior change", "cohort", "comorbidity", "experimental study", "frailty", "immune activation", "immune function", "improved", "in vitro Model", "in vivo", "inflammatory marker", "inhibitor", "memory CD4 T lymphocyte", "military veteran", "mouse model", "peripheral blood", "prevent", "terminally differentiated effector memory (TEM) T cells", "translation to humans", "translational goal", "viral rebound" ], "approved": true } } ], "meta": { "pagination": { "page": 1385, "pages": 1442, "count": 14420 } } }