HIV and the Brain: New Challenges in the Modern Era PDF
Preview HIV and the Brain: New Challenges in the Modern Era
CURRENT CLINICAL NEUROLOGY Series Editor: Daniel Tarsy, MD Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA For other titles published in this series, go to www.springer.com/series/7630 Robert H. Paul • Ned Charlton Sacktor Victor Valcour • Karen Tokie Tashima Editors HIV and the Brain New Challenges in the Modern Era Editors Robert H. Paul, PhD Ned Charlton Sacktor, MD Department of Psychology Johns Hopkins University School of Medicine Behavioral Neuroscience Johns Hopkins Bayview Medical Center University of Missouri – St. Louis Baltimore, MD, USA St. Louis, MO, USA Victor Valcour, MD Karen Tokie Tashima, MD Department of Geriatric Medicine Alpert Medical School of Brown University John A. Burns School of Medicine The Miriam Hospital University of Hawaii Providence, RI, USA Honolulu, HI, USA and Memory and Aging Center Department of Neurology UCSF San Francisco, CA, USA ISBN: 978-1-93411-508-4 ISBN: 978-1-59745-434-6 (eBook) DOI: 10.1007/978-1-59745-434-6 Library of Congress Control Number: 2008943241 © Humana Press, a part of Springer Science+Business Media, LLC 2009 All rights reserved. This work may not be translated or copied in whole or in part without the written pemrission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, Nwe York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, n either the authors nor the editors nor the publisher can accept an y legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper springer.com Series Editor’s Introduction It is now more than a quarter century since the appearance of the ifrst reported cases of the acquired immunodeficiency syndrome (AIDS). Although successful treat- ments with highly acti ve antiretroviral therapies have made a major impact on survival, there still remains no vaccine for prevention and the available therapies do not cure the disease. As a result, AIDS has been transformed into a chronic, lifelong disease which requires continuous antiretro viral drug treatment together with ongoing treatment of the associated systemic medical complications. It appears that as survival improves, the prevalence of chronic central nervous system involvement may be increasing. As pointed out by the editors of this volume, this shift in emphasis requires further examination of how AIDS affects the brain in terms of cogniti ve function, neuropsychiatric manifestations, activities of daily living, and quality of life. They also go on to ask the interesting question of how AIDS involvement of the brain interacts with normal aging. In HIV and the Brain, Drs. Paul, Sacktor, Valcour, and Tashima have assembled an impressive international team of experts to summarize the current state of knowl- edge concerning brain function in AIDS. Early chapters re view epidemiology, pathophysiology, neuropathology, neuroimaging, and HIV genetics followed by a series of chapters concerning the neuropsychological, behavioral, and neuropsychi- atric aspects of the disease. Finally, several chapters are devoted to examining the interaction of the aging brain on the expression of AIDS-related cognitive impair- ment. This volume is largely directed to a clinical audience with the hope of advancing multidisciplinary translational research that may serv e to increase the understanding of how HIV affects the brain. The sobering statement by the editors that AIDS may be the most common cause of dementia among people under age 40 should lend impetus to the importance of more ef fectively dealing with this most dreaded complication of the disease. Daniel Tarsy, MD Professor of Neurology Harvard Medical School Vice Chair, Department of Neurology Beth Israel Deaconess Medical Center Boston, MA v Preface The history of human immunodeficiency virus (HIV) is very familiar to clinicians and researchers invested in this field, and a number of e xcellent texts have been published that provide contemporary summaries of the disease. This remains true in terms of the impact of the virus on the brain, which is an area of focus that has been appreciated since the early period of the HIV epidemic. Based on this, one may ask why yet another book is needed that specif ically focuses on HIV and the brain. Below we answer this question and in the process establish the rationale, purpose, and scope of this important and timely contribution to the field. Although treatment of HIV with highly acti ve antiretroviral therapy (HAART) has become standard in the developed world, and more common in the developing countries, no current therapies “cure” HIV. This has resulted in HIV transitioning from a time-limited, f atal disease to a chronic condition that requires constant medical intervention. As such, whereas in the past clinical care pro viders and the scientific community may have largely focused on efforts to prevent mortality prior to the availability of HAART, there is now a greater focus on addressing factors that negatively impact overall quality of life among individuals infected with HIV who are surviving the disease in the conte xt of chronic treatment. This paradigm shift has brought brain function associated with HIV into the clinical forefront because the impact of the virus on the brain is directly related to cogniti ve capacity, the expression of neuropsychiatric symptoms, independence in activities of daily living (including medication adherence), and ultimately patients’ percei ved ratings of quality of life. In addition to the general recognition noted above that brain function is now an important aspect of both HIV -related clinical care and research, ne w areas of emphasis have emerged in the modern era of the HIV pandemic that w arrant an update on HIV and the brain. In part, these changes reflect outcomes associated with a population of patients who are living longer, such as the impact of HIV on the brain in the context of chronic, long-term treatment with HAART, as well as the potential synergistic effects of HIV and advanced age on cognitive outcomes. The HIV population is aging, in part due to the longer survi val times associated with treatment and there is concern that HIV , like many other medical factors, may interact with the aging process to increase cognitive burden among patients. Finally, a focus on international studies of brain dysfunction in the conte xt of HIV has vii viii Preface emerged within the last decade, and this work may offer important insights into the neuropathogenesis of brain impairment associated with the virus. HIV includes multiple genetic strains (clades), and reports suggest potential dif ferences in bio- logical properties and neurovirulence across these clades. Answering these issues is complicated by the global geographic distribution of the clade subtypes, and the inherent need to conduct cross-cultural studies of neuropsychological function. Several chapters in this book review this literature and provide guidance and insight for future studies. The purpose of this edited v olume is to summarize the e xtant knowledge of brain function in the conte xt of chronic treatment, interactions between age and HIV on the brain, and international studies of brain involvement with an emphasis on clade diversity. Scientif c authorities in each of the three areas ha ve provided comprehensive and insightful reviews of the literature. Each chapter is written with a clinical audience in mind, and while the science is of suff cient rigor to serve as an important resource for basic scientists, a major goal of this book is to present the science in a manner that is ultimately useful to both bench scientists as well as clinical researchers and clinical-care providers. Ideally, a book that is attractive to these audiences will f acilitate the development of future transdisciplinary and translational studies to further de velop our understanding of HIV and the brain. Given current estimates that HIV may be the most common cause of dementia worldwide among individuals under the age of 40, the research re viewed and guidelines proposed within this book are both timely and important in a global and international context. University of Missouri St. Louis, St. Louis, MO, USA Robert H. Paul Johns Hopkins University, Baltimore, MD, USA Ned C. Sacktor UCSF, San Francisco, CA, USA Victor Valcour Brown University, Pawtucket RI, USA Karen T. Tashima Contents 1 Neurocognitive Changes in AIDS: Evolution of Treatment of HIV Infection ....................................................................................... 1 Erna Milunka Kojic and Charles C.J. Carpenter 2 Global Incidence and Epidemiology of the AIDS Pandemic, Distribution of HIV Subtypes, and Epidemiology of Hepatitis C Infection Among HIV-Positive Individuals ....................................... 9 Karen T. Tashima and Aadia I. Rana 3 New Insights into HIV Neuropathogenesis ............................................ 17 Tory P. Johnson and Avindra Nath 4 Neuropathological Findings Associated with Long-Term HAART ........................................................................ 29 Iain C. Anthony and Jeanne E. Bell 5 Biomarkers of HIV-Related Central Nervous System Disease ............ 49 Bruce James Brew and Scott Letendre 6 Neuroimaging Among HIV-Infected Patients: Current Knowledge and Future Directions ........................................... 75 David F. Tate, Jared J. Conley, Dominik S. Meier, Bradford A. Navia, Ronald Cohen, and Charles R.G. Guttmann 7 The Assessment of HIV-Associated Neurocognitive Disorders: New Challenges in the HAART Era ....................................................... 109 Lucette A. Cysique and Bruce J. Brew 8 The Changing Face of HIV-Associated Cognitive and Neuropsychiatric Disturbance ......................................................... 133 Ron Cohen ix x Contents 9 Youth with HIV/AIDS: Neurobehavioral Consequences ................... 187 Susannah Allison, Pamela L. Wolters, and Pim Brouwers 10 Co-Occurrence of HIV, Hepatitis C, and Substance Use Disorders: Effects on Brain Functioning ...................................... 213 Raul Gonzalez, Phillip J. Quartana, and Eileen M. Martin 11 The Functional Impact of HIV-Associated Neuropsychological Decline .................................................................. 233 Matthew J. Wright, Ellen Woo, Terry R. Barclay, and Charles H. Hinkin 12 Adjunctive Therapy for Long-Term Support of Cognitive Impairment ....................................................................... 249 Joshua T. Dearborn, Susan E. Maloney, Nicole Hicklin, Elizabeth M. Lane, and Robert Paul 13 HIV-1 Genetic Diversity and Its Biological Significance .................... 267 Michael M. Thomson 14 Opportunistic Infections in the Brain in Developing Countries ........................................................................ 293 Marcus Tulius T. Silva and Beatriz Grinsztejn 15 Impact of Clade Diversity on Neuropsychological Outcomes ............ 319 Robert Paul, Ned Sacktor, Lucette Cysique, Bruce Brew, and Victor Valcour 16 The Effects of Aging on HIV Disease ................................................... 331 Robert C. Kalayjian and Lena Al-Harthi 17 Neuropsychology of Healthy Aging ...................................................... 347 Molly E. Zimmerman and Adam M. Brickman 18 Interactions Between Advanced Age and HIV Cognitive Impairment............................................................................ 369 Victor Valcour and Aaron M. McMurtray Index ................................................................................................................ 393 Contributors Lena Al-Harthi Graduate Program in Immunology and Microbiology, Rush Medical College, Chicago, IL, USA Susannah Allison Infant, Child, & Adolescent Research Programs, Center for Mental Health Research on AIDS, Division of AIDS & Health and Behavior Research, National Institute of Mental Health, NIH, Bethesda, MD, USA Iain C. Anthony Centre for Infectious Diseases, University of Edinburgh, Edinburgh, Scotland Terry R. Barclay HealthEast Hospitals and Clinics, Department of Psychology, St. Paul, MN, USA Jeanne E. Bell Pathology (Neuropathology), University of Edinburgh, Western General Hospital, Edinburgh, Scotland Bruce J. Brew University of New South Wales, Sydney, NSW, Australia; Department of Neurology, St. Vincent’s Hospital, Victoria St. Darlinghurst, NSW, Australia Adam Brinkman Department of Neurology, College of Physicians and Surgeons, Columbia University, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, New York, NY, USA Pim Brouwers Infant, Child, & Adolescent Research Programs, Center for Mental Health Research on AIDS, Bethesda, MD, USA Charles C.J. Carpenter Brown University, Providence, RI, USA xi
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