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Parenteral Inhibitors of HIV Entry in Current Development The R7694_2_REM_VE_COV_2_2_01.qxd 31/10/06 12:08 Page 2 VOLUME 2 NUMBER 2 2006 EDITORS-IN-CHIEF Graeme Moyle, Chelsea and Westminster Hospital, London, UK Jacob Lalezari, UCSF, San Francisco, CA, USA Parenteral Inhibitors of HIV Entry in Current Development Jacob Lalezari, Stanley Lewis, G Mani Subramanian, Richard Krawiec, and Mary K Delmedico The Mechanism and Inhibition of Influenza Entry Zhu-Nan Li and David A Steinhauer What is the Role for HIV-Entry Inhibitors in Microbicides? Per Johan Klasse Meeting Report from AIDS 2006 www.viralentry.com This activity has been planned and implemented in accordance This journal is supported by an with the Essential Areas and Policies of ACCME through the joint educational grant from Pfizer. sponsorship of the University of Kentucky College of Medicine and Remedica. The University of Kentucky College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. The University of Kentucky is an equal opportunity university. R7694_2_REM_VE_COV_2_2_01.qxd 31/10/06 12:08 Page 3 The Journal of Viral Entry is supported by an educational grant from Pfizer Editorial Policy Publisher’s Statement The Journal of Viral Entry is an independent journal published by Remedica Medical Education © Remedica Medical Education and Publishing 2006. and Publishing. Editorial control is the sole responsibility of the Editors-in-Chief, Editorial Advisory Board, and the Editors. Before publication, all material submitted to the journal is subjected to All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, rigorous review by the Editors-in-Chief, Editorial Advisory Board, Editors, and/or independent or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or reviewers for suitability of scientific content, scientific accuracy, scientific quality, and conflict otherwise without the prior permission of the copyright owners. While every effort is made by the publisher and editorial board to see that no inaccurate or misleading data, opinions, or statements of interest. appear in this journal, they wish to make it clear that the material contained in the publication Aims and Scope represents a summary of the independent evaluations and opinions of the authors and contributors. The Journal of Viral Entry is designed to bring a critical analysis of the world antiviral medicine As a consequence, the board, publishers, and any supporting company accept no responsibility for literature, written by clinicians, for clinicians, to an international, multidisciplinary audience. Our the consequences of any such inaccurate or misleading data or statements. Neither do they endorse mission is to promote better understanding of antiviral medicine across the global healthcare the content of the publication or the use of any drug or device in a way that lies outside its current system by providing an active forum for the discussion of clinical and healthcare issues. licensed application in any territory. Leading Articles The Journal of Viral Entry (ISSN 1748-0329) is published twice a year. Subscriptions are available These major review articles are chosen to reflect topical clinical and healthcare issues at the following rates: Europe Eur65, USA and Canada and all other territories US$85. Additional in antiviral medicine. All contributions undergo a strict editorial review process. subscription information is available from the publisher. Clinical Reviews Remedica Medical Education and Publishing Ltd., Commonwealth House, 1 New Oxford Street, The most important papers from the best of the international literature on antiviral medicine London WC1A 1NU, UK. are systematically selected by an internationally recognized panel of experts. The Editors then Telephone: +44 (0)20 7759 2999 Fax: +44 (0)20 7759 2951 prepare concise and critical analyses of each paper, and, most importantly, place the findings Editorial Team: Cecilia Waller, Scott Millar into clinical context. Editorial Director: Reghu Venkatesan Meeting Reports Design and Artwork: AS&K Skylight Creative Services The Journal of Viral Entry also provides incisive reportage from the most important Publishers: Ian Ackland-Snow, Simon Kirsch international congresses. ISSN 1748-0329 R7694_2_REM_VE_2_2_07.qxd 2/11/06 16:39 Page 2 Editors-in-Chief Contents Graeme Moyle Medical Director, St Stephen’s HIV Research, Editorials Chelsea and Westminster Hospital, London, UK Prevention and Therapeutics Jacob Lalezari Graeme Moyle and Jacob Lalezari 46 Assistant Clinical Professor of Medicine, Mount Zion Recent Results with CCR5 Antagonists Hospital of UCSF, and Director, Quest Clinical Research, Graeme Moyle and Jacob Lalezari 47 San Francisco, CA, USA Editorial Advisory Board Leading Articles Parenteral Inhibitors of HIV Entry David Cooper in Current Development Director and Professor of Medicine, National Centre in HIV Jacob Lalezari, Stanley Lewis, Epidemiology and Clinical Research, Sydney, NSW, Australia G Mani Subramanian, Richard Krawiec, and Mary K Delmedico 48 Robert Doms Chair, Department of Microbiology, University of Pennsylvania The Mechanism and Inhibition of Influenza School of Medicine, Philadelphia, PA, USA Virus Entry J Michael Kilby Zhu-Nan Li and David A Steinhauer 57 Associate Professor of Medicine, Medical Director, UAB 1917 (HIV) Clinic, Associate Director, UAB Pittman Commentary What is the Role for Entry Inhibitors in General Clinical Research Center, University of Alabama Microbicides for Blocking Transmission at Birmingham, Birmingham, AL, USA of HIV-1 via the Cervico–Vaginal or Peter Reiss Rectal Mucosa? Deputy Director of the Dutch National AIDS Therapy Per Johan Klasse 67 Evaluation Center (NATEC), Academic Medical Center, Clinical Reviews University of Amsterdam, Amsterdam, The Netherlands Coreceptors 73 Jonathan Schapiro Drug Interactions 73 Adjunct Clinical Professor, Center for AIDS Research, Stanford University School of Medicine, Stanford, CA, USA, Drug Resistance and Susceptibility 74 and Director, AIDS Service, National Hemophilia Center, Viral Variants 75 Tel Hashomer, Israel Antiretroviral Therapy 75 Vincent Soriano Service of Infectious Diseases, Instituto de Salud Carlos III, Meeting Report Madrid, Spain The 16th International AIDS Conference (AIDS 2006) Editors Toronto, ON, Canada, 13–18 August, 2006 77 James Hellinger Assistant Professor, Division of Infectious Diseases, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA Andrew Luber Consultant, Division of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA Mike Youle Director, Royal Free Centre for HIV Medicine, Royal Free Hospital, London, UK R7694_2_REM_VE_2_2_07.qxd 2/11/06 16:39 Page 46 Prevention and Therapeutics Graeme Moyle1 and Jacob Lalezari2 1St Stephen’s HIV Research, Chelsea and Westminster Hospital, London, UK 2Mount Zion Hospital of University of California and Quest Clinical Research, San Francisco, CA, USA J Viral Entry 2006:2(2):46. EDITORIAL This year’s 16th International AIDS conference in Toronto, fusion inhibitors. As reviewed by Jacob Lalezari (Mount Zion ON, Canada, and ICAAC in San Francisco, CA, USA, Hospital of University of California and Quest Clinical brought two themes to the fore: prevention and new Research, San Francisco, CA, USA) and colleagues, a treatments. The rising burden of HIV infection is number of these compounds are parenteral formulations disproportionately impacting lives, life expectancy, and that offer the potential of improved pharmacokinetic economies in many of the world’s poorest nations, creating properties and/or sustained release profiles, which might a vicious cycle. The limited availability and relatively high allow once-weekly, or even once-monthly, dosing. Although cost (relative to gross domestic product or health spend) of parenterally administered agents are unlikely to compete as antiretroviral drugs has not been sufficient to act as a public first- or second-line agents in most settings, their emergence health measure, although they do provide benefits to many could result in greater treatment choices for patients in need individuals. Similarly, the disappointingly slow progress on of salvage therapy. vaccine development means that this option remains As a journal of viral entry, the scope of in this issue distant, at best. As the majority of HIV transmissions occur expands to include a comprehensive discussion by Zhu-Nan through sexual intercourse, easy access to an inexpensive Li and David A Steinhauer (Emory University School of topical product, such as a microbicide preparation that is Medicine, Rollins Research Center, Atlanta, GA, USA) of the protective against HIV transmission and not an irritant to mechanism of entry of the influenza virus. The interaction the vaginal or rectal mucosa, would be highly attractive. between influenza viral hemagglutinin (HA) and host cell Furthermore, microbicides offer the advantage of a means surface glycoproteins containing sialic acid results in of protection that the passive party in a relationship can conformational changes within HA that produce a fusion control and potentially use without their sexual partner’s peptide – a helical coiled coil structure – that, like gp41 of knowledge. Such an agent would complement other HIV, is propelled to the target cell surface to mediate entry preventative measures including condoms, circumcision, into the cell. Interestingly, as noted by Li and Steinhauer, this and one day, hopefully, vaccinations.
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