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.

Pregnancy rates and clinical outcomes among women living with HIV enrolled in HPTN 052

Abstract: ABSTRACT HPTN 052 was a multi-country clinical trial of cART for preventing heterosexual HIV-1 transmission. The study allowed participation of pregnant women and provided access to cART and contraceptives. We explored associations between pregnancy and clinical measures of HIV disease stage and progression. Of 869 women followed for 5.70 (SD = 1.62) years, 94.7% were married/cohabitating, 96% initiated cART, and 76.3% had >2 past pregnancies. Of 337 women who experienced pregnancy, 89.3% were from countries with lower contraceptive coverage, 56.1% first started cART with PI-based regimens and 57.6% were 25–34 years old. Mean cART duration and condom use were similar among pregnant and nonpregnant individuals. Adjusting for confounders, viral load suppression (VLS) was not (aHR(CI) = 0.82(0.61, 1.08)) and CD4 was slightly associated with decreased rates of first pregnancy over time (aHR(CI) = 0.9(0.84, 0.95)); baseline VLS was associated with increased (aRR(CI) = 2.48(1.71, 3.59)) and baseline CD4 was slightly associated with decreased number of pregnancies (aRR(CI) = 0.9(0.85,0.96)) over study duration. Partner seroconversion was univariably associated with higher rates of first pregnancy (HR(CI) = 2.02(1.32,3.07)). Despite a background of higher maternal morbidity and mortality rates, our findings suggest that becoming pregnant does not pose a threat to maternal health in women with HIV when there is access to medical care and antiretroviral treatment.

P692 Gentamicin susceptibility to neisseria gonorrhoeae in malawi after twenty-five years of sustained use

Abstract: Background Gentamicin has been used exclusively for the treatment of Neisseria gonorrhoeae (GC) in Malawi, since 1993. Previous gentamicin susceptibility testing in 1993, 1996 and 2007, showed ≥95% susceptibility by both agar dilution and E-test. However, clinical cure rates 1–2 weeks following treatment, have been in the 90% range. We are in the process of repeating this assessment to inform treatment guidelines. Methods We are enrolling HIV-infected men presenting with acute urethritis at the sexually transmitted infections (STI) clinic at Bwaila District Hospital in Lilongwe, Malawi. All participants provide urethral swabs for STI etiologic testing, and are treated syndromically per Malawian standard of care, with gentamicin 240 mg IM, doxycycline 100 mg, BID for 7 days, and metronidazole 2g single dose. Patients are seen one week post-treatment for repeat clinical exam and GC culture. All specimens with a positive GC culture are tested locally for gentamicin susceptibility via E-test. E-test inhibition with ranges from 0-4, 4-16, and ≥16 are categorized as high, moderate, and low susceptibility, respectively. Clinical cure is determined by genital examination. Results 42 men with gonococcal urethritis have been enrolled to date. Baseline gentamicin E-test results: high susceptibility: 0-1: 21%; 1-2: 60%; 2-4: 19%; moderate or low susceptibility ≥4: 0%. 37/42 men (88%) returned for follow-up. 4/37 (11%) were culture positive for GC, including 2 (5%) symptomatic men. 3/4 (75%) of the week one E-test results were in the high susceptibility range, and 1/4 (25%) was in the low susceptibility range (≥16). Conclusion Based on our E-test results, all of the baseline GC isolates appear to be susceptible to gentamicin. However, at one-week follow-up, ∼11% continued to be infected with GC. Determining if these are treatment failures, re-infections or new infections is a challenge. Laboratory comparisons of matched isolates are planned to help categorize these concerning results. Study enrollment continues. Disclosure No significant relationships.

HIV postexposure prophylaxis after sexual assault: why is it so hard to accomplish?

Abstract: In this issue of Sexually Transmitted Diseases, Du Mont et al.1 described a study of 318 adolescent females seeking care for sexual assault in Ontario, Canada. The study focuses on HIV prevention after sexual assault and produced findings consistent with earlier studies2: although the majority of women were eligible for postexposure prophylaxis (PEP), most (57%) chose not to initiate therapy, and only a third actually completed a course of therapy. How can we account for the poor performance of this intervention? By any measure, the young women in this study seem highly motivated to protect their health. Indeed, they all sought health care after an assault. In their analysis, the investigators noted a number of factors, which made study subjects more likely to choose ART, such as a high level of anxiety (OR, 4.6) and student status (OR, 2.21). The most important influencing factor, however, was directive action (strong support for PEP) from the health care provider (OR 5.6). But 70% of the time, the healthcare provider was neutral (noncommittal) about PEP even though 84% of the subjects were eligible for treatment. Of those eligible, 94% were offered PEP. These results suggest that the problem with PEP lies as much with the providers as the patients who are victims of assault. In most instances, providers are likely unsure about the value of PEP. This should come as no surprise since there are simply no human data to prove that HIV PEP works for sexual exposure nor is there research on how best to use it in humans. PEP guidelines were established based on research with rhesus macaques (reviewed in Ref.3). In the macaque model, vaginal HIV transmission occurs slowly4 or swiftly,5 depending on the details of exposure. Prophylaxis with tenofovir can reliably prevent infection in macaques if started promptly (less than 72 hours after exposure) and when continued for 28 days. These observations form the basis for HIV PEP protocol in humans. The only human randomized clinical trials data reflect the very visible success of PEP to prevent mother-to-child (postpartum) HIV transmission,6 but the biology of such transmission is simply far too different from sexual exposure to justify comparison. And clearly it is difficult, if not impossible, to make PEP cost-effective unless the intervention is limited to the highest risk groups,7 which is inconsistent with most guidelines. As a result, health care providers have received very mixed messages. Sexual exposure to HIV in humans carries a very heterogeneous transmission probability.8 However, the risk is often conveyed as 1/1000 episode of intercourse, a number which clearly leads some victims to conclude that their risk of contracting HIV is low. But transmission probability rises dramatically during anal intercourse, or when genital tract viral load is high, or when inflammation or ulcers or traumatized tissues are present.4,8 These are largely “invisible” risks, undetectable during an assault, or even in the context of a prior relationship between victim and assailant. Indeed, the fact that subjects in the current report1 were less likely to chose ART if they knew their assailant for more than 24 hours is particularly alarming. In this study of subjects who were given initial PEP, fully two thirds stopped therapy. Some subjects might have accurately determined that their risk was much lower than initially perceived, but it seems likely that most victims were bothered by the inconvenience and/or side effects of the treatment and concluded the risk was too low to justify it. When health care providers believe that a history of possible HIV exposure justifies therapy, victims are best served when offered emergent, “front loaded” therapy and a follow-up when the victim is calmer. This is the strategy that seems to have been used in Ontario: a 4-day ART “starter-pack” and a follow-up visit. The drug choices also matter. In the Ontario study, subjects received a 3-drug regimen of combivir and kaletra. Although studies have suggested that 2-drug PEP regimens are better tolerated,9 use of 3 drugs seems wise to prevent outgrowth of a resistant HIV variant, and such variants are certainly not rare.10 Drugs that get into the female genital tract at the highest concentration and with the greatest speed seem best suited for PEP.11 HIV PEP is here to stay, and preventing even a single case of HIV makes it well worthwhile.12 This study from Ontario, howCorrespondence: Myron S. Cohen, MD Director, UNC Institute of Global Health and Infectious Disease Chief, Division of Clinical Infectious Diseases, 130 Mason Farm Road, Suite 2115, CB #7030 UNC Chapel Hill, Chapel Hill, NC 27514. E-mail: mscohen@med. unc.edu. Received for publication July 15, 2008, and accepted September 25, 2008. The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Sexually Transmitted Diseases, December 2008, Vol. 35, No. 12, p.979–980 DOI: 10.1097/OLQ.0b013e31818f2af4 Copyright © 2008, American Sexually Transmitted Diseases Association All rights reserved.

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.