Myron S. Cohen

Bio: Myron S. Cohen is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Population & Acquired immunodeficiency syndrome (AIDS). The author has an hindex of 103, co-authored 549 publications receiving 46021 citations. Previous affiliations of Myron S. Cohen include University of Massachusetts Medical School & Scripps Health.

Models for predicting effective HIV chemoprevention in women.

Abstract: OBJECTIVE Model systems that rapidly identify tissue drug concentrations protective of HIV infection could streamline the development of chemoprevention strategies. Tissue models are promising, but limited concentration targets exist, and no systematic comparison to cell models or clinical studies has been performed. DESIGN We explored the efficacy of maraviroc (MVC) and tenofovir (TFV) for HIV prevention by comparing Emax models from TZM-bl cells to vaginal tissue explants and evaluated their predictive capabilities with a dose-challenge clinical study. METHODS HIV-1JR-CSF was used for viral challenge. Drug efficacy was assessed using a luciferase reporter assay in TZM-bl cells and real-time PCR to quantify spliced RNA in a tissue explant model. Cell and tissue concentrations of MVC, TFV, and the active metabolite tenofovir diphosphate were measured by liquid chromatography with tandem mass spectrometry and used to create Emax models of efficacy. Efficacy after a single oral dose of 600 mg MVC and 600 mg tenofovir disoproxil fumarate was predicted from cell and tissue models and confirmed in a clinical study with viral biopsy challenge postdose. RESULTS TFV was >10-fold and MVC >1000-fold, more potent in TZM-bl cells compared with vaginal explant tissue. In the dose-challenge study, tissues from 3 of 6 women were protected from HIV infection, which was 49% lower than predicted by TZM-bl data and 36% higher than predicted by tissue explant data. CONCLUSIONS Comparative effective concentration data were generated for TFV and MVC in 3 HIV chemoprophylaxis models. These results provide a framework for future early investigations of antiretroviral efficacy in HIV prevention to optimize dosing strategies in clinical investigations.

The anti-SARS-CoV-2 monoclonal antibody, bamlanivimab, minimally impacts the endogenous immune response to COVID-19 vaccination

Abstract: As the coronavirus disease 2019 (COVID-19) pandemic evolves and vaccine rollout progresses, the availability and demand for monoclonal antibodies for the prevention and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also accelerating. This longitudinal serological study evaluated the magnitude and potency of the endogenous antibody response to COVID-19 vaccination in participants who first received a COVID-19 monoclonal antibody in a prevention study. Over the course of 6 months, serum samples were collected from a population of nursing home residents and staff enrolled in a clinical trial who were randomized to either bamlanivimab treatment or placebo. In an unplanned component of this trial, a subset of these participants was subsequently fully vaccinated with two doses of either SpikeVax (Moderna) or Comirnaty (BioNTech/Pfizer) COVID-19 mRNA vaccines. This post hoc analysis assessed the immune response to vaccination for 135 participants without prior SARS-CoV-2 infection. Antibody titers and potency were assessed using three assays against SARS-CoV-2 proteins that bamlanivimab does not efficiently bind to, thereby reflecting the endogenous antibody response. All bamlanivimab and placebo recipients mounted a robust immune response to full COVID-19 vaccination, irrespective of age, risk category, and vaccine type with any observed differences of uncertain clinical importance. These findings are pertinent for informing public health policy with results that suggest that the benefit of receiving COVID-19 vaccination at the earliest opportunity outweighs the minimal effect on the endogenous immune response due to prior prophylactic COVID-19 monoclonal antibody infusion. Description Individuals infused with an anti–SARS-CoV-2 antibody demonstrated a robust immune response to subsequent COVID-19 vaccination. Minimal impact As vaccines for SARS-CoV-2 became widely available, so too did monoclonal antibodies as therapeutics and prophylactics. Here, Benschop et al. investigated the impact of prior prophylactic treatment with a SARS-CoV-2 monoclonal antibody, bamlanivimab, on the response to vaccination with Comirnaty or SpikeVax in a cohort of nursing home residents and staff. They observed that the effect of prior bamlanivimab treatment on vaccination was minimal, suggesting that the benefits of monoclonal antibody therapy outweigh the costs in terms of reducing vaccine-elicited immune responses.

Epidemic Hemorrhagic Fever Revisited

Abstract: Epidemic hemorrhagic fever is a disease characterized by phases of sequential fever, hypotension, oliguria, and polyuria. This disease represented a major hazard for American soldiers during the Korean War (1950-1953) and is a persistent problem in Asia, the USSR, and northern Europe. Advances in the etiology, epidemiology, and therapy of epidemic hemorrhagic fever are discussed.

HIV Linkage to Care and Retention in Care Rate Among MSM in Guangzhou, China.

Abstract: Quantifying HIV service provision along the HIV care continuum is increasingly important for monitoring and evaluating HIV interventions. We examined factors associated with linkage and retention in care longitudinally among MSM (n = 1974, 4933 person-years) diagnosed and living in Guangzhou, China, in 2008–2014. We measured longitudinal change of retention in care (≥2 CD4 tests per year) from linkage and antiretroviral therapy initiation (ART). We examined factors associated with linkage using logistic regression and with retention using generalized estimating equations. The rate of linkage to care was 89% in 2014. ART retention rate dropped from 71% (year 1) to 46% (year 2), suggesting that first-year retention measures likely overestimate retention over longer periods. Lower CD4 levels and older age predicted retention in ART care. These data can inform interventions to improve retention about some subgroups.

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Abstract: Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Role of free radicals and catalytic metal ions in human disease: an overview.

Abstract: Publisher Summary This chapter discusses the role of free radicals and catalytic metal ions in human disease. The importance of transition metal ions in mediating oxidant damage naturally leads to the question as to what forms of such ions might be available to catalyze radical reactions in vivo . The chapter discusses the metabolism of transition metals, such as iron and copper. It also discusses the chelation therapy that is an approach to site-specific antioxidant protection. The detection and measurement of lipid peroxidation is the evidence most frequently cited to support the involvement of free radical reactions in toxicology and in human disease. A wide range of techniques is available to measure the rate of this process, but none is applicable to all circumstances. The two most popular are the measurement of diene conjugation and the thiobarbituric acid (TBA) test, but they are both subject to pitfalls, especially when applied to human samples. The chapter also discusses the essential principles of the peroxidation process. When discussing lipid peroxidation, it is essential to use clear terminology for the sequence of events involved; an imprecise use of terms such as initiation has caused considerable confusion in the literature. In a completely peroxide-free lipid system, first chain initiation of a peroxidation sequence in a membrane or polyunsaturated fatty acid refers to the attack of any species that has sufficient reactivity to abstract a hydrogen atom from a methylene group.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Abstract: 1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Sexually transmitted diseases treatment guidelines.

Abstract: The MMWR series of publications is published by the Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.