HIV-associated neurocognitive disorders (HAND) remain an important cause of cognitive dysfunction. Current nomenclature for HAND includes HIV-associated dementia and milder forms known as asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND). ANI and MND remain highly prevalent despite combined antiretroviral therapy (cART). These mild forms of HAND must be diagnosed through neuropsychological testing. If a patient has HAND, it remains unclear whether using a cART regimen with theoretically superior CNS penetration improves the prognosis. Nevertheless, a CNS penetration effectiveness score for antiretrovirals is available. Other factors to consider when diagnosing and treating HIV infection and HAND include the HIV clade or subtype. Data suggest that HAND occurs more often in association with certain clades, and higher vigilance for cognitive dysfunction may be recommended. Finally, comorbidities, such as diseases associated with advanced age, other infections, and drug abuse, need to be considered as cofactors for cognitive dysfunction and treated accordingly.
Abstract This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.
This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.
Important advances have been made in recent years in identifying the molecular mechanisms of HIV neuropathogenesis. Defining the pathways leading to HIV dementia has created an opportunity to therapeutically target many steps in the pathogenic process. HIV itself rarely infects neurons, but significant neuronal damage is caused both by viral proteins and by inflammatory mediators produced by the host in response to infection. Highly active antiretroviral therapy (HAART) does not target these mediators of neuronal damage, and the prevalence of HIV-associated neurocognitive dysfunction has actually been rising in the post-HAART era. This review will briefly summarize our current understanding of the mechanisms of HIV-induced neurological disease, and emphasize translation of this basic research into potential clinical applications.
This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of North American (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists, and dermatologists in North America. It is important to realize that guidelines cannot always account for individual variation among patients. They are assessments of current scientific and clinical information provided as an educational service; are not continually updated and may not reflect the most recent evidence (new evidence may emerge between the time information is developed and when it is published or read); should not be considered inclusive of all proper treatments methods of care, or as a statement of the standard of care; do not mandate any particular course of medical care; and are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Whether and the extent to which to follow guidelines is voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances. Although IDSA, AAN, and ACR make every effort to present accurate, complete, and reliable information, these guidelines are presented “as is” without any warranty, either express or implied. IDSA, AAN, and ACR (and their officers, directors, members, employees, and agents) assume no responsibility for any loss, damage, or claim with respect to any liabilities, including direct, special, indirect, or consequential damages, incurred in connection with these guidelines or reliance on the information presented. The guidelines represent the proprietary and copyrighted property of IDSA, AAN, and ACR. Copyright 2020 Infectious Diseases Society of America, American Academy of Neurology, and American College of Rheumatology. All rights reserved. No part of these guidelines may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of IDSA, AAN, or ACR. Permission is granted to physicians and healthcare providers solely to copy and use the guidelines in their professional practices and clinical decision-making. No license or permission is granted to any person or entity, and prior written authorization by IDSA, AAN, or ACR is required, to sell, distribute, or modify the guidelines, or to make derivative works of or incorporate the guidelines into any product, including but not limited to clinical decision support software or any other software product. Except for the permission granted above, any person or entity desiring to use the guidelines in any way must contact IDSA, AAN, or ACR for approval in accordance with the terms and conditions of third party use, in particular any use of the guidelines in any software product. Summarized below are the 2020 recommendations for the prevention, diagnosis, and treatment of Lyme disease. The panel followed a systematic process used in the development of other Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation) (see Figure 1). A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text (http://onlinelibrary.wiley.com/doi/10.1002/art.41562/abstract). A. Personal protective measures B. Repellents to prevent tick bites C. Removal of attached ticks A. Diagnostic tick testing B. Diagnostic testing of asymptomatic patients following tick bites Supplementary data. Supplementary materials (in addition to the full guideline) are available on the Arthritis & Rheumatology website at http://onlinelibrary.wiley.com/doi/10.1002/art.41562/abstract. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author. Conflict of interest statement. See the Methodology section in the full guideline (on the Arthritis & Rheumatology website at http://onlinelibrary.wiley.com/doi/10.1002/art.41562/abstract) for approach to conflict of interest (COI) by the IDSA/AAN/ACR COI review group. The following list is a reflection of what has been reported to the IDSA/AAN/ACR COI review group. To provide thorough transparency, the IDSA/AAN/ACR requires full disclosure of all relationships, regardless of relevancy to the guideline topic. The assessment of disclosed relationships for possible COI is based on the relative weight of the financial relationship (i.e., monetary amount) and the relevance of the relationship (i.e., the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. Dr. Lantos has received research funding from the National Cytomegalovirus Foundation and from the NIH and educational funding from Duke University; and has served as a consultant and reviewed trial protocol for Frederick O’Connor Medical Consultants, LLC. Dr. Bockenstedt has received research funding from the NIH and the Gordon and Llura Gund Foundation; has received remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research; and was awarded an endowed professorship as the Harold W. Jockers Professor of Medicine at Yale University. Dr. Falck-Ytter serves as director of the Evidence Foundation and the GRADE Network; conducts GRADE workshops with the Evidence Foundation; has served as the chair of the Guidelines Committee for the American Gastroenterological Association; and has received research funding from the Cleveland VA Medical Research and Education Foundation. Dr. Aguero-Rosenfeld serves as a council member for the New York City chapter of the American Society of Microbiology (ASM) and as a Board member of the American Lyme Disease Foundation; has provided legal testimony and consultation regarding Lyme disease and tick-borne diseases; and has received research grants from the NIH, BioFire, New York State Department of Health, and ViraMed. Dr. Auwaerter receives research funding from the Fisher Center for Environmental Infectious Diseases and the NIH; serves on the Board of Directors of the American Lyme Disease Foundation and as the Vice Chair of the Infectious Diseases Society of America (IDSA) Foundation; serves as a scientific advisor for DiaSorin, Adaptive Technologies, and Shionogi; provides legal expert opinion testimony regarding Lyme disease; had stock in Johnson & Johnson; has served as an editor for Johns Hopkins POC-IT ABX Guide, an advisor for the Food and Drug Administration (FDA), Genentech, Dynavax, Aradigm, Cempra, BioMérieux, Cerexa, and Medscape; has received research funding from Cerexa; has served on the FDA Advisory Board, the Medscape Advisory Board, and the IDSA Board of Directors; and his spouse has equity interest in venture capital–funded Capricor. Dr. Belani reviews non-continuing medical education (CME) lectures for and received honoraria and travel reimbursement from Horizon Therapeutics; and has received research funding from the NIH and the Children’s Hospitals and Clinics of Minnesota. Dr. Bowie has provided expert testimony to the Canadian Senate Subcommittee on Bill C-442: An Act Respecting a National Lyme Disease Strategy on behalf of the Association of Medical Microbiology and Infectious Disease Canada; and has received research funding from GlaxoSmithKline, Pfizer Canada, the Canadian Institutes of Health Research, and Vancouver Coastal Health Research Institute. Dr. Branda receives research funding from the Lyme Disease Biobank Foundation and Zeus Scientific; serves as a scientific advisor and consultant to DiaSorin, Inc.; has served as a scientific advisor and consultant for T2 Biosystems; has served on the scientific advisory board of Roche Diagnostics and AdvanDx; has received research funding from Karius, Inc., Alere, Inc., T2 Biosystems, BioMérieux, TBS Technologies, Immunetics, Inc., DiaSorin, Inc., Kephera Diagnostics, Inc., and the Bay Area Lyme Foundation; has participated in unfunded research collaborations with Karius Inc. and Kephera Diagnostics; was a member of the editorial board of the Journal of Clinical Microbiology; was a co-inventor on an application for a patent to protect intellectual property; and his spouse is an employee of Informed DNA. Dr. Clifford receives research funding from the NIH and the Alzheimer’s Association; serves as scientific consultant to Inhibikase and Excision BioTherapeutics; serves on Data and Safety Monitoring Boards (DSMB) for Biogen, Genzyme/Sanofi, Genentech, EMD Serono, Shire, Wave Life Sciences, Pfizer, Atara, Mitsubishi Tanabe, and IQVIA (formerly Quintiles); serves on Progressive Multifocal Leukoencephalopathy (PML) adjudication committees for Amgen, GlaxoSmithKline, EMD Serono, Bristol Myers Squibb, Roche, and the Takeda Oncology (formerly Millennium) Adjudication Committee–FDA, as well as Dr. Reddy’s Laboratories; has previously received research funding from the NIH; and his spouse formerly held stock in Johnson & Johnson. Dr. DiMario has received research funding from Novartis. Dr. Halperin serves as an Editorial Board Member of Neurology, and Vice Chair of the American Academy of Neurology (AAN) Guideline Subcommittee; has stock in Abbott Labs, AbbVie, Merck, and Johnson & Johnson; provides and has previously provided legal expert testimony defending physicians in medical malpractice cases on various neurologic issues, including Lyme disease; has received research funding from NIH, the Centers for Disease Control and Prevention (CDC); and has served as a section editor of neuroinfectious diseases in Neurology & Neuroscience Reports. Dr. Krause receives research funding from the Yale Emerging Infections Program; receives remuneration from Gold Standard Diagnostics for a collaborative research project; has stock in Gilead Sciences and First Trust NASDAQ Pharmaceuticals ETF; has received research funding from the NIH, the Centers for Disease Control and Prevention (CDC), the Gordon and Llura Gund Foundation, and L2 Diagnostics for NIH-sponsored research; has served as a scientific consultant and provided medical education and training for Oxford Immunotec, Inc.; has a patent pending (Enhanced Chemiluminescent enzyme-linked immunosorbent assay for detection of antibodies against Babesia microti), for which US Provisional Patent Application No. 62/580,588, was filed on November 2, 2017; serves on the Board of Directors for the American Lyme Disease Foundation and the Editorial Boards of Pathogens and Plos Neglected Tropical Diseases and the Editorial Advisory Board of Clinical Infectious Diseases; was on the Editorial Board of Journal of Clinical Microbiology, and will be on the Editorial Board of Clinical Microbiology Reviews starting January 2021. Dr. Liang has stock in Johnson & Johnson; received research funding from the Veterans Health Administration, the Arthritis Foundation, and the NIH; has served on the FDA Advisory Panel, Institute of Medicine panels; served as a scientific reviewer for the Research Grant Council of Hong Kong and the NIH; served on the Board of the Lupus Clinical Trials Consortium, Beacon Hill Villages, and Rx Foundation and advised the Institute for Clinical and Economic Review and the China Medical Board; previously had stock in Sequenom; and his spouse has stock in Johnson & Johnson. Dr. Meissner is a current member of the CDC Workgroups and serves as a volunteer consultant on the American Academy of Pediatrics Committee on Infectious Diseases and the NIH DSMB. Dr. Nigrovic receives research funding from the NIH, Department of Defense, and the NIH Center for Research Resources and for Advancing Translational Sciences (NCATS), Global Lyme Alliance, and Peabody Foundation; serves on the Editorial Board for Annals of Emergency Medicine; has served as scientific consultant for Adaptive Technologies; has received research funding from the NIH, Provider and Payer Quality Initiative (PPQI) Research Foundation, Harvard Catalyst, Hood Foundation, Bay Area Lyme Foundation, CDC, Emergency Medical Services for Children (EMSC), the National Patient-Centered Clinical Research Network (PCORNet), Milton Foundation, and Boston Children’s Hospital. Dr. Nocton receives research funding from Bristol Myers Squibb; serves as a member of the Subboard of Pediatric Rheumatology of the American Board of Pediatrics; and has received research funding from AbbVie, NIH, and the Arthritis Foundation. Dr. Pruitt has received research funding from Teva Pharmaceuticals and has served on the AAN Editorial Board of Neurology Clinical Practice. Ms Rips has received research funding from the Center for AIDS Research, Biogen Idec, Hoffmann-LaRoche, Sun Pharmaceutical Industries Ltd., Genzyme, the Alzheimer’s Association, and the American College of Radiology; and has served as a speaker for Teva Pharmaceuticals. Dr. Rosenfeld serves as a Council Member of the American College of Cardiology; has stock in Abbott, Proctor & Gamble, and General Electric; has received Fellowship Support from Boston Scientific, Medtronic, and Abbott Laboratories (formerly St. Jude Medical); has received research funding from Boehringer Ingelheim Pharmaceuticals, Inc.; and has served on the Program Committee and the Patient and Caregivers Committee of the Heart Rhythm Society. Dr. Savoy serves on the American Academy of Family Physicians (AAFP) Board of Directors, as an ex-officio Board member of Delaware Academy of Family Physicians (DAFP), as the Chair of the Centers for Medicare and Medicaid Services (CMS) Advisory Panel on Outreach and Education, and as Secretary of the Board of Directors of the Association of Departments of Family Medicine; receives honoraria from AAFP, DAFP, CMS, and Merck; has served on an Advisory Council for Highmark Health and as an advisor to the AAFP Adolescent Immunization Project; has received honoraria from AAFP; has served as the President of DAFP, as Editor of DelFamDoc, and as a member of AAFP Commissions. Dr. Sood has received research funding from the NIH; and has provided expert testimony for Danaher Lagnese, PC. Dr. Steere receives research funding from the NIH and the Mathers Foundation; has received research funding from the NIH, the American College of Rheumatology, the Mathers Foundation, the English-Bonter-Mitchell Foundation, Immunetics, Inc., Zeus Diagnostics, and the Ounsworth-Fitzgerald Foundation; and has served as a scientific advisor for Baxter Bioscience Institute of Systems Biology, Immunetics, Inc., Roche Diagnostics, and Viramed. Dr. Strle receives research funding from the Slovenian Research Agency; serves as the Head of Health Counsel of the Ministry of Health of the Republic of Slovenia and as a member of the Steering Committee for the European Society of Clinical Microbiology and Infectious Diseases Study Group for Lyme Borreliosis; serves on the Roche Diagnostics Advisory Board on Lyme Disease Diagnostics; and has received honoraria from Roche Diagnostics. Dr. Sundel receives research funding from the NIH and AbbVie, Inc.; serves as a content author and editor for UpToDate; provides expert testimony to Chin-Caplan, PC; has provided expert testimony for Conway Homer, PC; has served as an advisor for Paul Hastings, LLC; has served as a content editor for SimulConsult and as a Medical Education Resources lecturer for CME-granting educational courses; has received remuneration from SimulConsult as a co-investigator for an NIH-sponsored grant; and has received research funding from the NIH. Dr. Tsao receives research funding from the National Science Foundation, NIH, CDC, the Michigan Lyme Disease Association, and the Michigan Department of Health and Human Services; serves as a Scientific Council Advisor Member for the Canadian Lyme Disease Research Network and as a scientific advisor for the American Lyme Disease Association; has received research funding from Michigan State University; has served as an Associate Editor for Ticks and Tick-Borne Diseases and on the Tick Vectors, Surveillance, and Prevention Subcommittee of the US Department of Health and Human Services Tick-Borne Disease Working Group; and has received remuneration for providing educational seminars for Boehringer Ingelheim (formerly Merial). Dr. Wormser receives research funding from Immunetics, Inc., Rarecyte, Inc., Institute for Systems Biology, and Quidel Corporation; serves on the Board of the American Lyme Disease Foundation; provides and has previously provided expert testimony in malpractice cases; has stock in AbbVie, Inc. and Abbott Laboratories; has received research funding from the CDC, NIH, BioMérieux, Bio-Rad Laboratories, and DiaSorin, Inc; has served as a scientific research advisor for Baxter International and as a Lyme disease advisor and expert for the Missouri Board of Registration for the Healing Arts; has a patent approved (US patent no. 10,669,567 B2) for High Sensitivity Method for Early Lyme Disease Detection; filed 2 patent applications related to early Lyme disease detection (application no: 62/277,252) and Lyme arthritis and post-treatment Lyme disease syndrome (application no: 62/725,745); and has served on the Editorial Boards for Clinical Infectious Diseases, Vector-Borne and Zoonotic Diseases, and Ticks and Tick-Borne Diseases. Dr. Zemel has served as an advisor for Novartis Promotional Speakers Bureau. No other disclosures relevant to this article were reported. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. The expert panel expresses its gratitude for thoughtful reviews of an earlier version to the external reviewers. The panel thanks the IDSA, AAN, and ACR for supporting the guideline development process. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Lantos had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Lantos, Rumbaugh, Bockenstedt, Falck-Ytter, Aguero-Rosenfeld, Auwaerter, Baldwin, Bannuru, Belani, Bowie, Branda, Clifford, DiMario, Halperin, Krause, Lavergne, Liang, Meissner, Nigrovic, Nocton, Osani, Pruitt, Rips, Rosenfeld, Savoy, Sood, Steere, Strle, Sundel, Tsao, Vaysbrot, Wormser, Zemel. Lantos, Rumbaugh, Bockenstedt, Falck-Ytter, Aguero-Rosenfeld, Auwaerter, Baldwin, Bannuru, Belani, Bowie, Branda, Clifford, DiMario, Halperin, Krause, Lavergne, Liang, Meissner, Nigrovic, Nocton, Osani, Pruitt, Rosenfeld, Savoy, Sood, Steere, Strle, Sundel, Tsao, Vaysbrot, Wormser, Zemel. Lantos, Rumbaugh, Bockenstedt, Falck-Ytter, Aguero-Rosenfeld, Auwaerter, Baldwin, Bannuru, Belani, Bowie, Branda, Clifford, DiMario, Halperin, Krause, Lavergne, Liang, Meissner, Nigrovic, Nocton, Osani, Pruitt, Rips, Rosenfeld, Savoy, Sood, Steere, Strle, Sundel, Tsao, Vaysbrot, Wormser, Zemel. 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