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.

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

Abstract: Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

Point-of-Care Diagnostics for Acute HIV Infection: An Important Public Health Priority

Abstract: To the Editor—We appreciate the correspondence in this issue of the Journal by Jones et al and Laperche et al evaluating the performance of the Alere Determine HIV-1/2 Ag/Ab Combo test (Combo point-of-care test [POCT]) for the detection of antibodies for established human immunodeficiency virus (HIV) infection and p24 antigen for acute HIV infection (AHI) [1, 2]. We believe that the earliest stages of HIV infection, including AHI, are critical for both individual health and HIV prevention. During AHI, establishment of latency currently renders HIV infection incurable. Persons with AHI also have high viral loads, making them highly contagious for a brief period. AHI therefore represents an important time for intervention [3]. Identification of subjects with AHI is critical, yet challenging. Since persons are antibody-negative during AHI, HIV rapid tests, which detect HIV antibodies, cannot detect AHI. AHI can be detected only with diagnostics capable of identifying HIV RNA, DNA or p24 antigen. To date, most of these diagnostics have been laboratory-based. In a recent issue of the Journal, we evaluated the Combo POCT, a test designed to concomitantly detect HIV antibodies and p24 antigen in separate reading frames at the point of care [4]. Our study was conducted among persons attending a sexually transmitted infection clinic and an HIV testing and counseling center in Lilongwe, Malawi. We found that the antibody portion of the test had excellent sensitivity and specificity for detecting established HIV infection. However, the antigen portion of the test had zero sensitivity and inadequate specificity for detecting AHI. The antigen portion of the test was unable to identify any of the 8 persons with true AHI, and it falsely classified 6 HIV-uninfected persons as having AHI. Such incorrect results could cause considerable mental anguish, confusion, and cost. Jones et al report similar findings among high-risk persons in the United Kingdom [1]. The antibody portion of the Combo POCT had excellent sensitivity and specificity, but the antigen portion of the test had poor sensitivity and specificity. It did not identify the 2 persons with AHI, and it incorrectly classified 2 HIV-uninfected and 1 antibody-positive person as having AHI. They also noted several invalid tests and implementation challenges owing to a narrow reading interval. Laperche et al assess the sensitivity of the Combo POCT at different p24 concentrations and among different clades in archived plasma and stored supernatants [2]. Even in these laboratory settings, the Combo POCT was unable to detect p24 consistently, especially with non-B subtypes. Although laboratory testing can be an important early step for gauging when a test may or may not perform adequately, it simply cannot replace field testing, which is required to determine ultimate utility. This is especially important for a test like the Combo POCT, which is designed to be used at the point of care on finger-stick whole blood. Laperche et al note the difficulty of field testing for AHI. However, we and others have demonstrated the feasibility of this approach. We have reported elsewhere that AHI can be detected routinely in the sexually transmitted infection setting where we conducted our analysis [5], allowing us to conduct ongoing studies related to this stage of HIV disease [6–7]. Although the performance of the antigen portion of the Combo POCT has been disappointing, the goal of identifying persons during AHI is important [8]. Investigators and industry should work together toward designing sensitive and specific diagnostics that can detect AHI at the point of care. These diagnostics must then be field tested before clinical use, regardless of the degree of difficulty involved.

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.