This book is dedicated to the visionary leaders of the Academic Alliance for AIDS Care in Africa, a model for care-based professional training and research as an indispensable means of ending the AIDS pandemic. FM-X2882.indd ii 7/20/2007 2:33:42 PM An imprint of Elsevier Inc © 2008, Elsevier Inc. All rights reserved. Chapter 69 © Tony Barnett. The material in Chapter 63 is in the public domain and may be used and reprinted without special permission; citation of the source, however, is appreciated. First published 2008 No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the Publishers. Permissions may be sought directly from Elsevier’s Health Sciences Rights Department, 1600 John F. Kennedy Boulevard, Suite 1800, Philadelphia, PA 19103-2899, USA: phone: (+1) 215 239 3804; fax: (+1) 215 239 3805; or, e-mail: Preface The fi rst edition of this book’s predecessor, The off-patent production along with pharmaceutical Medical Management of AIDS, appeared in 1988, at a subsidies and governmental distribution are allow- time when care for even the most economically priv- ing millions of patients access to potent treatment. ileged sought to ameliorate but not reverse what was Although huge challenges remain, hope is now pos- then an invariably fatal disease. The epidemic in less sible for those areas most in need in confronting the advantaged areas such as Africa was barely men- scourge of HIV along with tuberculosis, malaria, and tioned, and antiretroviral therapy, primarily zidovu- the crushing poverty and gender inequalities that dine monotherapy, had only modest benefi t. serve as the stage on which the epidemic often The next six editions of The Medical Management of unfolds. AIDS saw great changes. By 1999, when the sixth The editors of the prior volume hope that this edition appeared, multi-drug antiretroviral regi- book’s re-birth as Global HIV/AIDS Medicine addresses mens had begun to reverse AIDS mortality trends in both the hope of newer treatment and the challenges the US and other resource-rich countries, and had that remain to be addressed for this hope to be real- been shown to dramatically decrease transmission ized globally. Additional editors have brought new from infected women to their infants. The incidence expertise to the book’s leadership, and many new of formerly common opportunistic infections and authors and topics make this the fi rst textbook aimed malignancies had decreased, and HIV infection was at a comprehensive approach to the management of increasingly seen as a chronic, albeit still serious, what is truly a global problem. The editors hope that disease. Still, in 1999, almost no one dared hope that this effort can play a valuable role in extending the similar benefi ts could be achieved in Africa, Asia, or incredible advances of HIV/AIDS therapy to the other resource-constrained regions. many millions still in desperate need. Much has changed by this edition’s publication in 2007. Antiretroviral regimens have become Paul A. Volberding, Merle A. Sande more convenient, less toxic, and, in resource-limited Warner C. Greene, Joep M. A. Lange, Joel E. Gallant settings, often much less expensive. Generic and xi FM-X2882.indd xi 7/20/2007 2:33:43 PM List of Contributors Donald I. Abrams MD Tony Barnett BA (Hons), MA Sahai Burrowes MALD Director of Clinical Programs (Econ), PhD International Projects Manager Osher Center for Integrative ESRC Professorial Research Center for HIV Information Medicine Fellow University of California San Professor of Clinical Medicine LSE Health Francisco University of California San London School of Economics San Francisco, CA Francisco London USA San Francisco, CA UK USA Oluma Y. Bushen MD John G. Bartlett MD Associate Director Frederick L. Altice MD Professor of Medicine Tulane University Technical Associate Professor of Medicine Division of Infectious Diseases Assistance Program Yale University AIDS Program The John Hopkins University Addis Ababa Yale University School of Medicine Ethiopia New Haven, CT Baltimore, MD USA USA Jayne Byakika-Tusiime Andrew Angelino MD BPharm, MSc Assistant Professor Paul R. Bohjanen MD, PhD PhD Candidate and Department of Psychiatry and Associate Professor of Epidemiologist Behavioural Sciences Microbiology and Medicine University of California Berkeley The Johns Hopkins University Department of Microbiology Berkeley, CA School of Medicine, University of Minnesota USA Baltimore, MD Minneapolis, MN USA USA Denise M. Cardo MD Director Cristian Apetrei MD, PhD Charles Boucher MD, PhD Division of Healthcare Quality Associate Professor Department of Virology Promotion Department of Microbiology Eijkman-Winkler Institute Centers for Disease Control and Tulane National Primate University Medical Center Prevention Research Center Utrecht Atlanta, GA Covington, LA Utrecht , The Netherlands USA USA David Bangsberg MD, MPH David R. Boulware MD, MPH, David J. Cennimo MD Associate Professor of Medicine DTMH Chief Medical Resident Department of Medicine Assistant Professor of Medicine Department of Medicine University of California San Department of Medicine New Jersey Medical School Francisco Division of Infectious Diseases Newark, NJ San Francisco, CA and International Medicine USA University of Minnesota USA Minneapolis, MN Richard E. Chaisson MD Jason D. Barbour PhD, MHS USA Professor of Medicine, Assistant Professor of Medicine Epidemiology and International Positive Health Program R. Douglas Bruce MD, MA Health San Francisco General Hospital Clinical Instructor of Medicine Johns Hopkins University University of California San Yale University AIDS Program Baltimore, MD Francisco Yale School of Medicine USA San Francisco, CA New Haven, CT USA USA xiii FM-X2882.indd xiii 7/20/2007 2:33:43 PM List of Contributors Marie Charles MD, MIA J. Lucian Davis MD W. Lawrence Drew MD, PhD Chair & CEO, International Clinical Instructor Director, Clinical Virology Center for Equal Healthcare Division of Pulmonary and Laboratory Access Critical Care Medicine and HIV/ Professor, Laboratory Medicine Henry Crown Fellow AIDS Division and Medicine The Aspen Institute San Francisco General Hospital Medical Center at Mount Zion Adjunct Professor, Columbia University of California San University of California San University, School of Francisco Francisco International and Public Affairs San Francisco, CA San Francisco, CA New York, NY USA USA USA Kevin M. DeCock MD, FRCP, Ernest Drucker PhD David B. Clifford MD DTM&H Professor of Epidemiology and Melba and Forest Seay Professor Director, HIV/AIDS Program Social Medicine of Clinical Neuropharmacology World Health Organization Montefi ore Medical Center Department of Neurology Geneva Albert Einstein College of Washington University School of Switzerland Medicine Medicine New York, NY St Louis, MO Steven G. Deeks MD USA USA Associate Professor of Medicine Positive Health Program James P. Dunn MD David A. Cooper MD, DSc San Francisco General Hospital Associate Professor of Professor of Medicine University of California San Ophthalmology National Centre in HIV Francisco The Wilmer Eye Institute Epidemiology and Clinical San Francisco, CA John Hopkins School of Medicine Research USA Baltimore, MD University of New South Wales USA Darlinghurst, NSW Inge Derdelinckx MD, PhD Australia Associate Professor Jerrold J. Ellner MD Department of Virology Professor and Chair Paul Coplan MSc, DSc, MBA Eijkman Winkler Institute Department of Medicine Senior Director, Risk University Medical Center New Jersey Medical School Management Utrecht Newark, NJ Global Safety Surveillance, The Netherlands USA Epidemiology and Labeling Wyeth Pharmaceuticals Emma Devitt MB BCh Kim S. Erlich MD Worldwide Special Lecturer in Medicine Assistant Clinical Professor of Collegeville, PA Medical Professorial Unit Medicine USA University College Dublin/Mater University of California San Hospital Francisco Ernest Darkoh-Ampem MD, Dublin San Francisco, CA MPH, MBA Ireland USA Chairman and Founding Partner BroadReach Healthcare Douglas Dieterich MD Oren K. Fix MD, MSc Washington, DC Professor of Medicine Assistant Professor of Medicine USA Department of Medicine Division of Gastroenterology Mount Sinai School of Medicine University of Washington New York, NY Medical School USA Seattle, WA USA xiv FM-X2882.indd xiv 7/20/2007 2:33:43 PM List of Contributors Charles W. Flexner MD Clive M. Gray MSc, PhD Richard L. Guerrant MD Professor of Medicine, Chief Specialist Scientist Thomas H. Hunter Professor of Pharmacology and Molecular Head of HIV Immunology International Medicine Sciences, and International HIV Immunology AIDS Research Division of Infectious Diseases Health Unit and International Health Division of Clinical National Institute for Director, Center for Global Pharmacology Communicable Diseases Health, Johns Hopkins University Johannesburg University of Virginia Baltimore, MD South Africa Charlottesville, VA USA USA Warner C. Greene MD, PhD Gerald Friedland MD Director, Gladstone Institute of Catherine Hankins MD, MSc, Professor of Medicine and Virology and Immunology FRCP(C) Epidemiology and Public Health Nick and Sue Hellman Endowed Chief Scientifi c Adviser and Director, AIDS Program Professor of Translational Biology Associate Director Yale New Haven Hospital Professor of Medicine, Policy, Evidence and Partnerships Yale School of Medicine Microbiology and Immunology UNAIDS New Haven, CT University of California San Geneva USA Francisco Switzerland San Francisco, CA Helene D. Gayle MD, MPH USA P. Richard Harrigan PhD President and Chief Executive Director Offi cer Deborah Greenspan BDS, DSc, Research Labs CARE USA FDSRCS British Columbia Centre for Atlanta, GA Leland and Gladys Barber Excellence in USA Distinguished Professor and HIV/AIDS Interim Chair Vancouver, BC Sibyl Geelen MD, PhD Department of Orofacial Sciences Canada Senior Consultant School of Dentistry Pediatric Infectious Disease University of California San Marianne Harris MD Specialist Francisco Clinical Research Advisor Center for Poverty-related San Francisco, CA AIDS Research Programme Communicable Diseases- USA St Paul’s Hospital PharmAccess Foundation Vancouver, BC Amsterdam John S. Greenspan BSc, BDS, Canada Department of Pediatric PhD, FRC Path, ScD(hc), Infectious Diseases FDSRCS (Eng) Robert Heimer PhD University Medical Center Professor and Dean for Research Professor of Epidemiology and Utrecht School of Dentistry Public Health The Netherlands Director Department of Epidemiology and AIDS Research Institute Public Health Trevor E. Gerntholtz MD School of Medicine Yale University School of Dumisani Mzamane African University of California San Medicine Institute of Kidney Disease Francisco New Haven, CT Chris Hani Baragwanath San Francisco, CA USA Hospital USA Soweto Hans V. Hogerzeil MD, PhD, South Africa Carl Grunfeld MD, PhD DSc, FRCP(Edin) Professor of Medicine Director Metabolism and Endocrine Medicines Policy and Standards Sections World Health Organization University of California San Geneva Francisco Switzerland San Francisco, CA USA xv FM-X2882.indd xv 7/20/2007 2:33:43 PM List of Contributors Laurence Huang MD Lawrence D. Kaplan MD Jeanne C. Keruly MS, CRNP Associate Professor of Medicine Professor of Medicine Assistant Professor of Medicine Chief, AIDS Chest Clinic University of California San Department of Medicine HIV/AIDS Division and Division Francisco Johns Hopkins University School of Pulmonary and Critical Care San Francisco, CA of Medicine Medicine USA Baltimore, MD Department of Medicine USA San Francisco General Hospital Elly Katabira MD University of California San Deputy Dean for Research Paul E. Klotman MD Francisco Faculty of Medicine Professor and Chair San Francisco, CA Makerere University Medical Division of Nephrology USA School Mount Sinai School of Medicine Kampala New York, NY Jula K. Inrig MD Uganda USA Instructor in Medicine Division of Nephrology Salim Abdool Karim MBChB, Jane E. Koehler MA, MD Department of Medicine PhD Professor of Medicine Duke University Medical Center Director Division of Infectious Diseases Durham, NC Centre for the AIDS Programme University of California San USA of Research Francisco South Africa San Francisco, CA Mark A. Jacobson MD Professor in Clinical USA Professor of Medicine in Epidemiology Residence Columbia University Richard A. Koup MD Positive Health Program Adjunct Professor in Medicine Chief, Immunology Laboratory University of California San Cornell University Vaccine Research Center Francisco New York, NY National Institute of Allergy and San Francisco, CA USA Infectious Diseases USA Bethesda, MD Anthony D. Kelleher PhD, MB USA Malcolm John MD, MPH BS, MD Assistant Clinical Professor Associate Professor of Medicine Oliver Laeyendecker MS, MBA Director, 360: The Positive Care National Centre in HIV Research Assistant Center at USCF Epidemiology and Division of Infectious Diseases Division of Infectious Diseases- Clinical Research Department of Medicine Department of Medicine University of New South Wales Johns Hopkins School of University of California San Darlinghurst, NSW Medicine Francisco Australia Baltimore, MD San Francisco, CA USA USA Stephen J. Kerr BPharm, MIPH, PhD Joep M. A. Lange MD, PhD Edward C. Jones-López MD, MS Biostatistician Center for Poverty-Related Assistant Professor of Medicine HIV Netherlands Australia Communicable Diseases Division of Infectious Diseases Thailand Resarch collaboration International AIDS Therapy and Center for Emerging (HIV-NAT) Evaluation Center Pathogens Bangkok University of Amsterdam New Jersey Medical School Thailand Amsterdam, The Netherlands Newark, NJ Senior Lecturer USA National Centre in HIV Epidemiology and Clinical Research University of New South Wales Sydney Australia xvi FM-X2882.indd xvi 7/20/2007 2:33:44 PM List of Contributors Joan C. Lo MD John R. Mascola MD Julio S. G. Montaner MD Assistant Professor of Medicine Deputy Director Professor of Medicine & Chair of Division of Endocrinology Vaccine Research Center AIDS Research San Francisco General Hospital National Institute of Allergy and University of British Columbia University of California San Infectious Diseases AIDS Research Program Francisco Bethesda, MD St Paul’s Hospital San Francisco, CA USA Vancouver, BC USA Canada Toby Maurer MD Jessica L. Long MD Associate Professor Jose G. Montoya MD Johns Hopkins School of Department of Dermatology Associate Professor of Medicine, Medicine, MS IV University of California San Division of Infectious Diseases JH Bloomberg School of Public Francisco and Geographical Medicine Health, MPH Candidate San Francisco, CA Stanford University School of Baltimore, MD USA Medicine USA Stanford, CA Concepta Merry MB, PhD, MSc, USA Primo Madra MD, PhD MRCPI National Program Offi cer Clinical Researcher Richard D. Moore MD UNFPA – Uganda Country Offi ce University of Makerere Professor of Medicine Kampala Kampala Department of Medicine Uganda Uganda John Hopkins University School of Medicine Kasia Malinowska-Sempruch Mark Mitchnick MD Baltimore, MD MSW Chief Scientifi c Consultant USA Program Director International Partnership for International Harm Reduction Microbicides Philippa Musoke MB, ChB Development Program (IHRD) East Hampton, NY Consultant Paediatrician Open Society Institute USA Paediatrics Department New York, NY Mulago Hospital USA Mesfi n Teshome Mitike MD Kampala Assistant Professor Uganda Simon Mallal MB BS, FRACP, Department of Internal Medicine FRCPA Faculty of Medicine Meg D. Newman MD Professor of Clinical Immunology Addis Ababa University Associate Professor of Clinical and Infectious Diseases Addis Ababa Medicine Centre for Clinical Immunology Ethiopia Positive Health Program at San and Biomedical Statistics Francisco General Hospital Royal Perth Hospital Jean-Paul Moatti PhD University of California San Perth, WA Professor of Health Economics Francisco Australia University of Mediterranean & San Francisco, CA INSERM USA Preston Marx PhD Marseilles Chair, Division of Microbiology France David Nolan MB BS, FRACP and Professor of Tropical Centre for Clinical Immunology Medicine Lynne M. Mofenson MD and Biomedical Statistics Tulane National Primate Chief, Pediatric, Adolescent and Royal Perth Hospital and Research Center Maternal AIDS Branch Murdoch University Covington, LA National Institute of Child Health Perth, WA USA and Human Development Australia Rockville, MD USA xvii FM-X2882.indd xvii 7/20/2007 2:33:44 PM List of Contributors Catherine Orrell MBChB, B. Matija Peterlin MD Peter Reiss MD, PhD MMed Professor of Medicine, Professor of Medicine Clinical Trials Manager Microbiology and Immunology Department of Infectious Infectious Diseases Unit Rosalind Russell Medical Diseases, Tropical Medicine and UCT Lung Institute Research Center AIDS University of Cape Town University of California San Academic Medical Center Cape Town Francisco Amsterdam South Africa San Francisco, CA The Netherlands USA Julie Overbaugh PhD Jack S. Remington MD Member, Division of Human Marion Peters MD Professor Emeritus Biology Chief of Hepatology Research Department of Medicine Fred Hutchinson Cancer Professor of Medicine Division of Infectious Diseases Research Center Division of Gastroenterology and Geographic Medicine Seattle, WA University of California San Stanford University School of USA Francisco Medicine San Francisco, CA Marcus A. Krupp Research Chair Kathleen R. Page MD USA and Chairman Instructor of Medicine Department of Immunology and Division of Infectious Diseases Marco Petrella Infectious Diseases Research Johns Hopkins University School Neurochem Inc. Institute of Medicine Québec Palo Alto Medical Foundation Baltimore, MD Canada Palo Alto, CA USA USA William G. Powderly MD, Adelisa L. Panlilio MD, MPH FRCPI Tobias F. Rinke de Wit PhD Medical Epidemiologist Professor of Medicine Professor of Sustainable Department of Healthcare Head, School of Medicine Diagnostics Quality Promotion University College Dublin School PharmAccess Foundation Centers for Disease Control and of Medicine Center for Poverty-related Prevention Dublin Communicable Diseases Atlanta, GA Ireland Academic Medical Center – USA University of Amsterdam Thomas C. Quinn MD, MSc Amsterdam Andrew T. Pavia MD Director The Netherlands Professor of Pediatrics and Johns Hopkins Center for Global Medicine Health Allan Ronald OC, FRSC, MD, Chief, Division of Pediatric Professor of Medicine, FRCPC, MACP Infectious Diseases International Health, Distinguished Professor Emeritus University of Utah Health Epidemiology, and Molecular Department of Internal Medicine Sciences Center Microbiology and Immunology University of Manitoba Salt Lake City, UT Johns Hopkins Medical Winnipeg, MB USA Institutions Canada Associate Director for Laurence Peiperl MD International Research Zeda F. Rosenberg ScD Associate Professor of Clinical Division of Intramural Research Chief Executive Offi cer Medicine National Institute of Allergy and International Partnership for University of California San Infectious Diseases Microbicides Francisco National Institutes of Health Silver Spring, MD San Francisco, CA Bethesda, MD USA USA USA xviii FM-X2882.indd xviii 7/20/2007 2:33:44 PM List of Contributors Kiat Ruxrungtham MD, MSc Hanneke Schuitemaker PhD James H. Stein MD Professor of Medicine Professor in Virology, Viro- Associate Professor of Medicine Department of Medicine pathogenesis of AIDS Cardiovascular Medicine Chulalongkorn University Department of Clinical Viro- Division Bangkok Immunology University of Wisconsin School of Thailand University of Amsterdam Medicine and Public Health Amsterdam Madison, WI Máirín Ryan BSc(Pharm), Dip The Netherlands USA Clin Pharm, Dip Health Econ, PhD Michael H. Serlin MD Steffanie Strathdee PhD Lecturer in Pharmacoeconomics Interim Chair of the Special Professor and Harold Simon National Centre for Services/HIV Department Chair Pharmacoenconomics Attending, Department of Division of International Health Trinity College Medicine and Cross Cultural Medicine Dublin Division of Infectious Diseases University of California School of Ireland North General Hospital Medicine Instructor, Department of Adjunct Professor Merle A. Sande MD Medicine John Hopkins Bloomberg School Professor of Medicine, University Mount Sinai School of Medicine of Public Health of Washington School of New York, NY USA Medicine USA President, Academic Alliance for Carlos S. Subauste MD AIDS Care and Prevention in James C. Shepherd MD, PhD Associate Professor Africa Adjunct Assistant Professor Departments of Ophthalmology USA Division of Infectious Diseases and Medicine Johns Hopkins School of Case Western Reserve University Morris Schambelan MD Medicine School of Medicine Professor of Medicine Baltimore, MD Cleveland, OH Associate Chair for Clinical and USA USA Translational Research University of California San Thira Sirisanthana MD Khuanchai Supparatpinyo MD Francisco Department of Medicine Associate Professor San Francisco, CA Chiang Mai University Hospital Department of Medicine USA Chiang Mai Faculty of Medicine, Thailand Chiang Mai University Hospital Mauro Schechter MD, PhD Chiang Mai Professor of Infectious Diseases Heather Southwell MS, RD Thailand University Federal do Rio de Research Dietitian Janeiro San Francisco VA Medical Center Lynda A. Szczech MD, MSCE Rio de Janeiro San Francisco, CA Assistant Professor Brazil USA Division of Nephrology Department of Medicine, Maarten F. Schim van der Loeff Papa Salif Sow MD Duke University Medical Center MD, MSc, PhD Professor of Infectious Diseases Durham, NC Senior Epidemiologist Dakar University Teaching USA Center for Poverty-related Hospital Communicable Diseases Dakar Feiko O. ter Kuile MD, PhD Academic Medical Center – Senegal Senior Clinical Lecturer University of Amsterdam Tropical Child Health Amsterdam Theo Sowa Liverpool School of Tropical The Netherlands Social Development Specialist Medicine London Liverpool UK UK xix FM-X2882.indd xix 7/20/2007 2:33:44 PM