BETA BULLETIN OF EXPERIMENTAL TREATMENTS FOR AIDS A publication of the San Francisco AIDS Foundation May 1992 CONTENTS: A Preview of the VIII International Conference on AIDS in Amsterdam Written and Compiled by John Willoughby A World United Against AIDS Jonathan Mann An AIDS Activist Perspective Holly Ladd Messages from the Conference Co-Chairs The Program for a Working Conference Descriptions of Session Types Finding Your Way Through the Conference The Minicourses Commercial and Non-Profit Satellite Meetings Priority Questions for the Harvard-Amsterdam Conference Marcus Conant, M.D. Research Notes Ronald A. Baker, Ph.D. FDA Antiviral Advisory Committee Recommendations on ddC and ddI Ronald A. Baker, Ph.D. Current Guidelines for Anti-HIV Therapy in Adults Hypericin for the Treatment of HIV Disease: An Update Bernard Bihari, M.D. Tat, Protease and the Hoffmann-LaRoche HIV Community Advisory Board Edwin B. Brown Glossary ********** A PREVIEW OF THE VIII INTERNATIONAL CONFERENCE ON AIDS AMSTERDAM, THE NETHERLANDS JULY 19-24, 1992 Sponsored by Harvard University and the Dutch Foundation-AIDS Welcome to Amsterdam! BETA has devoted a major part of the current issue to a preview of the 1992 International Conference on AIDS in Amsterdam, The Netherlands, sponsored by Harvard University and the Dutch Foundation- AIDS. John Willoughby of the Harvard AIDS Institute has prepared this comprehensive preview for publication in BETA. The 1992 International Conference on AIDS in Amsterdam is the largest ever, with over 7,000 delegates expected to participate. On arrival, they will encounter an unprecedented educational forum for people from all of the diverse sectors of the global HIV/AIDS community. Whether or not you attend the Harvard Amsterdam Conference, the articles, descriptions and charts in this preview offer you an insider view of the full range of new information, lively ideas and relevant issues that make up the Conference program. This BETA preview highlights many different aspects of the Conference, ranging from a complete listing of the satellite meetings to inclusive reviews of 10 minicourses on such subjects as Diagnosis and Management of Opportunistic Infections and HIV/ AIDS and the Commercial Sex Industry. State-of-the-Art discussion sessions, poster presentations, and report sessions on up-to-the-minute research results are other Conference events outlined in this preview. BETA and the San Francisco AIDS Foundation extend best wishes for a productive and enjoyable Conference to all delegates, and thank them for their continuing efforts to ameliorate the devastating effects of HIV disease. Ronald A. Baker, Ph.D. Editor, BETA ********** A WORLD UNITED AGAINST AIDS Jonathan Mann Jonathan Mann, Conference Chair of the VIII International Conference on AIDS, is Professor of Epidemiology and International Health at the Harvard School of Public Health, and founder of the World Health Organization's Global Program on AIDS. It has long been recognized that an effective effort against HIV/AIDS depends upon the full and active participation of all parties involved. This includes not only caregivers, scientists, and clinicians, but also individuals with HIV/AIDS, advocates, policy makers and affected communities. Therefore, when a concerted international effort failed to change unnecessary and unfair U.S. visa restrictions for people with HIV, the VIII International Conference on AIDS/III STD World Conference was relocated. The Conference will now take place in Amsterdam, the Netherlands, from 19-24 July 1992. "For the first time community-based and nongovernmental organizations, people with HIV/AIDS, and the developing world are represented on the International Steering Committee for the Conference and on the Conference Track Program Committees." In addition to relocating the conference, organizers of the Harvard-Amsterdam Conference have taken concrete steps to ensure that the full range of issues and questions involved in the global effort against HIV/ AIDS are included in this Conference. For example, for the first time community-based and nongovernmental organizations, people with HIV/AIDS, and the developing world are represented on the International Steering Committee for the Conference and on the Conference Track Program Committees. In addition, the Community Liaison Committee of the Conference has held meetings with and sent questionnaires to individuals and organizations throughout the world to solicit input on the identification of key issues to be addressed at the Conference. "When representatives of all sectors in the fight against HIV/AIDS gather together, certain advances and progress can occur in a way that is not possible at smaller, discipline-specific gatherings." When representatives of all sectors in the fight against HIV/AIDS gather together, certain advances and progress can occur in a way that is not possible at smaller, discipline-specific gatherings. Those from countries at an early stage of the epidemic, for instance, can learn from the successes and mistakes of those who have already passed through these stages; comparisons can be made and conclusions drawn from the differing approaches to prevention, diagnosis, treatment and public policy in different parts of the world; and the potential value of possible research directions can be more fully explored. To promote this process, the program for the VIII International AIDS Conference includes several innovations. Within each of the four subject tracks--Basic Science, Clinical Science and Care, Epidemiology, and Social Impact and Response--a number of key questions have been identified to be addressed at the Conference. These key questions focus on the central dilemmas of the HIV/AIDS pandemic, and point the way forward for future policy, practice and research. For example, questions in Clinical Science and Care include: What is the most current information concerning combination antiretroviral therapy, including alternating regimens? What are the respective roles of the patient and the care providers in integrating clinical, nutritional, psychosocial and complementary therapies in individual treatment strategies? What is the most current information regarding diagnostic methods, prophylaxis and therapy for the major opportunistic infections? What is the most current information regarding empirically used immune-based therapies, including the combination of specific and nonspecific immunomodulators? To make sure that the Conference fulfills its function of providing the most up-to-date and relevant information to participants, time has been reserved for "recent reports sessions," which will feature important research results that have occurred since the deadline for abstract submission. To enhance learning opportunities, all posters will be displayed throughout the entire Conference and will be discussed in thematic sessions; roundtable discussions will feature lively exchanges among experts holding diverse points of view on major issues; and each oral abstract session will have a discussant, whose role will be to put the new information, experience and ideas presented at the session into context for the audience, relating the research presented to the broader issues raised in the relevant key questions. The Conference has also organized ten minicourses which will combine both didactic and interactive methods in order to allow comprehensive coverage of specific problems and issues of particular importance. These minicourses cover a wide range of subjects, from Diagnosis and Management of Opportunistic Infections to Clinical Trials to Alternative, Complementary, and Traditional Therapies. ____________________________ PHOTO OMITTED ---------------------------- Left to right: Ernst Roscam Abbing, Co-Chair, Jonathan Mann, Chair, Joost Ruitenberg, Co-Chair "Recent reports sessions will feature important research results that have occurred since the deadline for abstract submission. All posters will be displayed throughout the entire Conference and will be discussed in thematic sessions." In addition to the formal Conference program, we also recognize the importance of the informal sessions and satellite meetings which take advantage of the presence in a single location of the world's experts in the many sectors of HIV/AIDS. Therefore, although the Conference cannot officially sponsor any satellite meetings, we have done all we can to encourage and facilitate them. At this stage in the HIV/AIDS pandemic, it is crucial that we all work together, applying the lessons of HIV/ AIDS within the health sector and beyond, and stimulating a truly global approach to this global public health threat. The 1992 Conference is based on our profound belief that we will learn--over time--to prevent and control the ravages of HIV infection and AIDS in our world. This capacity, the combined result of science and societal response, must be promoted, strengthened and accelerated. The Harvard- Amsterdam Conference provides the location and the opportunity for creative renewal of our efforts; by attending, each of us can contribute our energy, experience and resolve to move forward. ********** AN AIDS ACTIVIST PERSPECTIVE Holly Ladd Holly Ladd is Executive Director of the Boston AIDS Consortium. The 8th International AIDS Conference has begun to carve a new mission for future international meetings on the HIV epidemic. The success of its efforts will be measured first in Amsterdam, but the challenge for all of us will be to see changes initiated by the Dutch / Harvard meeting institutionalized in the planning for the 9th Conference in Berlin and the 10th meeting in Tokyo. The Conference Chair, Jonathan Mann from the Harvard School of Public Health, made a commitment to inclusion of both community-based organizations and non-governmental organizations in the process to plan and in the audience of the international meeting. Significant efforts also have been made to include people with HIV and women in all aspects of the planning to date. Has he been successful? Will it make a difference? Is there a reason for activists to travel to Amsterdam in July? Yes, both to share in the experience and to ensure that the positive changes are supported. The first major change in the conference was the development of the program around the so-called "key questions" facing those of us working on HIV in 1992. This change allowed the conference to select issues before selecting speakers, rather than trying to build a conference around the work of a few well-known presenters. Abstracts were selected for presentation based upon their response to the key questions. Round tables will be used in place of abstract presentations for more complex issues. Some topics that were key to activists and community providers raised questions where little work is being done and few abstracts were submitted. The lack of work in areas like transmission through oral sex, or the role that unacknowledged bisexuality plays in the spread of HIV in the developing world, suggests that these questions need to be asked during the conference in order to spur future research. Because some questions didn't fall within the established tracks of the Conference, the Executive Committee will schedule its own "complementary sessions. The interplay between reproductive rights and HIV, what those working on breast cancer can learn from the response to HIV and the role of activism, and the impact of the vaginal condom on prevention and education efforts are some of the topics that will find a special place in this year's conference. Along with the program changes and the attention to inclusion, the Conference Chair has made representation of developing countries a priority for the international meeting. Delegates from the developing world have never exceeded 11% of all attendees at previous conferences. The Conference has set an optimistic goal of 20% for the 8th International Conference. It will be important to see if the organizing efforts to bring people from Africa, Asia and South America are effective. For the first time the Conference will include a large, interactive meeting to discuss international concerns on access to care, information and treatment. Based on the model of a New England town meeting, the Global meeting will offer participants the opportunity to gather both at the beginning of the Conference as well as later in the week to see if a common agenda can be forged for the work ahead. The Global meeting, the inclusion of people from all continents and the enhancement of community-focused programming all promise a Conference that is relevant to our work and the problems we face. Can the Conference deliver? That remains to be seen. If it works, there will be a strong precedent and lobby to hold future Conference to the same standards. If it fizzles, than we can be sure that the German Conference in 1993 will look more like the disappointing experience of Florence "Science Challenges AIDS." There is an opportunity, despite the cost and the strain it puts on all of our agencies, to go to Amsterdam and "push the envelope," to see if the promise holds true, to learn and to share. It may even be the last opportunity to make the International AIDS Conferences inclusive of both science and community, providers, consumers and activists. We can be sure that it won' t happen without us. ********** MESSAGES FROM THE CONFERENCE CO-CHAIRS A Program Designed to Enhance Science Max Essex, Co-Chair for Science Mary Lasker Professor of Health Sciences in the Faculty of Public Health and Chairman of Cancer Biology at the Harvard School of Public Health When I attended the First International Conference on AIDS in 1985, scientists were just beginning to understand the most basic nature of the disease. Now, some 8 years later, we have made significant progress: the virus has been characterized, patchwork therapeutics have been developed, and our knowledge of the human immune system has advanced markedly. However, there is still a long way to go. "Every effort has been made to increase the representation and input of researchers from around the world, and particularly from developing countries." The International Conference on AIDS can make a real and lasting contribution to the progress we are all striving to achieve. In order to be of greatest value, the Conference must reflect the present course of the pandemic. For this reason, during the planning process of the Harvard-Amsterdam Conference, every effort has been made to increase the representation and input of researchers from around the world, and particularly from developing countries. In addition, several programmatic innovations have been developed to stimulate the international cooperation, collaboration, and joint problem-solving that are crucial to our future research efforts. ù Through the use of a set of "key questions," the Conference program has been designed not only to present the latest data, but to use this data to illuminate future research directions and clarify policy issues that affect research. ù Each abstract-driven session will have a discussant who will focus the sessions, highlighting agreement or disagreement among abstracts presented, and expediting assessment and analysis of information presented. ù For the first time, space will be reserved in the formal Conference program for "recent report sessions," enabling presentation of the most important developments that have surfaced in the months immediately preceding the Conference. ù For the first time, all posters will be displayed throughout the entire Conference, permitting delegates to take full advantage of the information presented by the posters. ù Mini-courses will be organized, combining both didactic and interactive methods to provide comprehensive analysis of particularly complicated or intractable research problems. More important than these innovations, however, is the fact that only at the Conference can each of us learn from experts not only in our field, but in all fields involved in the fight against HIV/AIDS. I urge each of you to attend. By gathering together, each contributing our individual information and expertise, we can significantly address the most difficult problems and issues of the epidemic. We can avoid duplication of effort, identify promising avenues of research, and by so doing perhaps mark a new era of cooperation in the work that we all share. STD World Congress and AIDS Conference Join Forces Yamil Kouri, Co-Chair for STDs Research Coordinator for Latin America and the Caribbean, Harvard Institute for International Development This year, for the first time, the International Conference on AIDS and the STD World Congress will meet concurrently, marking a historical juncture in our efforts to coordinate worldwide control of the spread of HIV infection and other sexually transmitted diseases. "This year, for the first time, the International Conference on AIDS and the STD World Congress will meet concurrently, marking a historical juncture in our efforts to coordinate worldwide control of the spread of HIV infection and other sexually transmitted diseases." The First STD World Congress was held in Puerto Rico in 1981, and the Second took place in Paris, France in 1986. While both meetings addressed the full range of STDs, AIDS was a significant topic of discussion at both, from initial reports of the disease at the First Congress to full awareness of the global magnitude of the pandemic at the Second. As we have learned more about HIV/AIDS over the years, the reasons for combining these 2 scientific meetings have become increasingly compelling. In most countries, sexual contact is the principle mode of transmission of HIV, and it has been clearly shown that the risk of such sexual transmission is enhanced by the concomitant presence of other sexually transmitted infections. These considerations, combined with the shortage of global health care resources and an increased awareness of common intervention strategies, have led many nations as well as national and international organizations to link HIV and STD prevention and control programs. By joining the primary international meetings of the 2 disciplines, we hope to spur this process, thus increasing our efficiency and success in combatting not only AIDS but all STD's. To ensure effective inclusion of international STD issues throughout the Conference program, the Conference has a co-chair for STDs, who is assisted by an STD advisory group. Members of this group include Peter Piot (Belgium), King Holmes (USA), J. Ndinya-Achola (Kenya), Ernesto Guerrero (Dominican Republic), and Y.F. Ngeow (Singapore). In addition, a member of each Program Committee has been designated to serve as an STD focal point, and individuals with STD expertise have been included on each of four International Program Track Committees. We believe that by merging our efforts we can be more effective in stopping the spread of HIV/AIDS than by working separately. Further, we hope that this example of inter-disciplinary cooperation is merely the first step in an international movement toward joint action in the face of massive public health challenges. ********** Societal Impact and Response Form a Complex Dynamic Paul Schnabel, Co-Chair for Impact/Response Director of Research at the Netherlands Institute of Mental Health and Professor of Mental Health at the University of Utrecht As the HIV/AIDS pandemic has expanded over the past decade, it has had an increasingly profound and direct impact not only on individuals, but also on national, regional, and international social and governmental structures. Every aspect of society, from medicine and health care delivery to fields as diverse as law, ethics, economics, and international tourism, has felt the consequences of the widening circle of this epidemic. The response of communities, nations, and international organizations to HIV/AIDS has varied widely. Some of the communities most severely affected have reacted with great strength and intensity of purpose. Through their response, these communities have brought profound change to our customary formulation of the doctor-patient relationship, to concepts of care and treatment, to traditional gender roles in family relationships, and to the mechanisms for developing drugs and therapies. Their work, dedication, and perseverance have made increasingly clear the importance and very real value of involving both individual patients and affected communities in the medical, scientific, and social responses to HIV/AIDS. "Some of the communities most severely affected have reacted with great strength and intensity of purpose. The impact of HIV/AIDS will only intensify in the coming years, and the ways in which our societies respond will directly effect the spread of the pandemic and therefore the ways in which those societies evolve and face an ever more complex future. In the continued absence of a vaccine or other effective preventive medical interventions, preventive behavior is the most important issue at hand. Only by changing behavior can we hope to bring the disease under control. It is therefore critical that the VIII International Conference on AIDS/III STD World Congress, as the premier international meeting devoted to the pandemic, give significant attention to the impact of HIV/AIDS and the range of possible responses to it. The Conference program has been designed to allow participants to do just that. While Track D has been specifically designated to highlight the scientific and behavioral research related to impact/response issues, all program tracks will devote time to these concerns. Through the key questions, each sector of the HIV/AIDS community will include in its formal program a consideration of how different communities are affected by HIV/AIDS, how these communities can best respond, and how communities and individual people with HIV can most effectively be involved in every aspect of the response to the pandemic. Particular attention must be paid to those groups who are heavily burdened by HIV/AIDS and yet are often underserved and underrepresented, including women in developing countries, children who become orphans or who are used as sex objects, and IV drug users around the world. By following this path, we will create a road map of our progress in contending with the epidemic, including our failures as well as our successes. By addressing these questions fully, we can not only illuminate the current responses to HIV/AIDS, but also assess where to apply efforts in the future. Over the past several years, the responses to HIV/ AIDS by individual communities affected by the epidemic, and by many community-based and non-governmental agencies, have been heroic and effective. However, AIDS is a worldwide problem. To effectively confront AIDS, these initial efforts must be expanded upon, joined together, and placed in a larger, global context. By considering the impact and response issues in all tracks, by combining our joint knowledge and experience, we can make a significant beginning on a coordinated, international response to HIV/AIDS that will lessen its impact. If we do this, we will begin to position ourselves and our colleagues worldwide to take full advantage of the remarkable advances of science in the face of this disease. ********** THE PROGRAM FOR A WORKING CONFERENCE The program of the 1992 International Conference on AIDS/III STD World Congress has been designed to provide critical, practical, applicable information about the HIV/AIDS pandemic. The meeting's goal--to advance our individual and collective efforts against AIDS --is apparent in the 3 essential innovations in the Conference program. The program is focused. For the first time, the Conference has been developed around the most critical questions and issues of the epidemic. The Conference will select speakers and abstract and poster presenters who can best address these questions in 4 areas: basic science, clinical science and care, epidemiology, and social impact and response. By identifying these key issues before the receipt of abstracts, the Conference can develop the most educational and useful program possible for delegates. The program is inclusive. The Conference key questions have been developed through unprecedented collaboration with hundreds of experts worldwide. Consequently, the program includes the contributions of the numerous groups essential to an effective response to AIDS, including basic scientists, clinicians, educators, people with HIV/AIDS, policy makers, people from community organizations and social scientists. This is the first time that such a broad spectrum of individuals has contributed to program development. The result is a Conference representing the issues most important to individuals from every AIDS discipline and from all geographic areas affected by the epidemic. The program is relevant. The key question format provides delegates with a road map of our progress in contending with the epidemic, including our successes and failures. Equally important, by addressing these questions fully, we can not only illuminate the current response to HIV/AIDS, but also assess where to apply efforts in the future. These questions therefore have important, practical implications for the most crucial research, policy, and resource allocation decisions in the year to come. ********** DESCRIPTIONS OF SESSION TYPES Below are descriptions of the various session formats which will be used in the Harvard-Amsterdam Conference. Unless otherwise noted, each session is scheduled to last approximately 1 hour. Multidisciplinary Plenaries: At each plenary session, experts in a variety of HIV/AIDS disciplines from all over the world will come together to address a core problem of our work. By considering the problem concurrently from a number of perspectives, the session will shed new light on the issue and contribute to progress toward a solution. The format for the plenaries consists of a brief introduction, presentations by each speaker, a discussion among the speakers about their respective presentations and a period of open discussion between speakers and audience. Each plenary will last approximately 80 minutes. State-of-the-Art Sessions: These sessions are designed to make complex and wide-ranging subjects accessible to the largest possible audience. While these sessions will make use of the latest data and scientific research, the emphasis will be on providing an updated summary of knowledge and experience on a key question relevant to HIV/AIDS. In these sessions, from 1 to 3 speakers will give short talks, followed by a question and discussion period. Roundtable Discussions: This format was chosen for the presentation of those key questions which are best served by a lively exchange among experts holding diverse points of view. In the roundtables, participants will present their individual views on controversial or problematic topics in HIV/AIDS, followed by a moderated discussion among the experts. A question and answer period will follow, and the facilitator will close the session with a brief summary highlighting the key points of the discussion. Oral Abstract Sessions: The 1992 Conference will include many traditional Oral Abstract sessions, in which 5 or 6 experts present summary results of their research and experience and respond to questions. To make sure that the educational potential of these presentations is fully realized, for the first time each abstract session will have a discussant, who will put the new information, experience, and ideas into context for the audience and relate the research presented to the broader issues raised in the relevant key questions. Poster Discussion Sessions: At this year's meeting, all posters will be on display throughout the entire Conference, and will be grouped together thematically. Poster discussion sessions will take place during the extended lunch periods of the Conference. In these sessions, expert moderators will highlight areas of agreement, disagreement, and uncertainty among posters in a single subject area, and will facilitate informal discussion and debate among participants and authors. Recent Report Sessions: For the first time, the 1992 Conference has reserved time in the formal program for the presentation of scientific research which has been completed between the deadline for abstract submission and the opening of the Conference. This research will be presented in the Recent Report Sessions on the first day of the Conference, thus ensuring that the very latest research in HIV/AIDS is presented to Conference attendees. Special Presentations: The objective of special presentations is to explore a specific issue or key question of HIV/AIDS in a flexible format. The format may include films, videos, or other artistic presentations in addition to featured speakers, or may cover topics which do not fit into existing sessions. Case Studies: These sessions will follow traditional case study format. A particular "case" will be presented briefly, after which the presenter will pose specific questions to a panel of experts. There will then be an open discussion among the experts and the audience, followed by summation. Minicourses: These courses, which are new to the International AIDS Conference, are designed to promote practical learning in a particular subject area. The courses will combine didactic presentation with interactive discussion between participants and program presenters. Each minicourse will be held on three consecutive afternoons--Tuesday 21 July, Wednesday 22 July, and Thursday 23 July--from 6.00 to 7.30 p.m. ********** FINDING YOUR WAY THROUGH THE CONFERENCE The International Conference on AIDS is the only meeting at which top experts from all facets of HIV/AIDS work come together to discuss their work. This is one of the Conference's great strengths. However, the sheer size of the program can sometimes seem overwhelming, and sorting through all of the sessions to find those of particular interest to you can become confusing. Below are brief "road maps" to the Conference, listing some sessions that will be of particular interest in selected subject areas. We have developed these pathways to provide examples of how delegates interested in particular areas might take best advantage of the Conference program. Please be aware that some time changes may have been made, and additional "supplementary" sessions added, since this printing: check your Final Program and the Conference daily newspaper to be sure of session times and titles. GENERAL THERAPY ISSUES ù Drug Therapy and Pathogenesis: (State-of-the-Art): Monday, July 20, 8:30 a.m. ù New Antiretrovirals: (Oral Abstract): Monday, July 20, 9:45 a.m. ù Combination Antiretroviral Therapies: (Poster Discussion): Monday, July 20, 1:00 p.m. ù Monitoring Surrogate Markers: Monday, July 20, 1:00 p.m. ù Indicators Measuring Quality of Life: Monday, July 20, 1:00 p.m. ù Combination Antiretroviral Therapy: (Oral Abstract): Monday, July 20, 2:30 p.m. ù Clinical Use of DDI/DDC: (Oral Abstract): Monday, July 20, 4:15 p.m. ù Treatment Regimens for PWAs: (Round Table): Tuesday, July 21, 9:45 a.m. ù Antiviral Drugs and Drug Resistance: (Poster Discussion): Tuesday, July 21, 1:00 p.m. ù Long-Term Studies of Early AZT Use: (State-of-the-Art): Wednesday, July 22, 8:30 a.m. ù Active & Passive Immunotherapy: (Round Table): Wednesday, July 22, 9:45 a.m. ù HIV Disease Progression, Co-Factors and Clinical Practice: Plenary: Wednesday, July 22,11:30 a.m. ù Virus Inactivation Procedures: (Poster Discussion): Wednesday, July 22,1:00 p.m. ù Effect of Antiviral Treatment on Infectiousness: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù HIV Treatment and Care for People with Hemophilia: (Oral Abstract): Thursday, July 22, 9:45 a.m. ù Treatment Priorities: Plenary: Thursday, July 22,11:30 a.m. ù Resistance to Anti-viral Therapy in HIV-1 and HSV: (Poster Discussion): Thursday, July 22,1:00 p.m. ù Most Current Immune-Based Therapies: (Poster Discussion): Thursday, July 22,1:00 p.m. ù Access to Care Systems: (Poster Discussion): Thursday, July 22, 4:15 p.m. ù Mixing Therapeutic Approaches: (Round Table): Thursday, July 22, 2:30 p.m. ù Choosing Therapies for Individual Treatment Strategies: (Round Table): Thursday, July 22, 4:15 p.m. Minicourses: ù Clinical Trials: Methods and Ethics: Tuesday, July 21-Thursday, July 23, 6:00 p.m. ù Alternative, Complementary and Traditional Therapies: Tuesday, July 21-Thursday, July 23, 6:00 p.m. TREATMENT OF OPPORTUNISTIC INFECTIONS: ù HlV-Related Malignancies: (Oral Abstract): Monday July 20, 2:30 p.m. ù STD Treatment Regimens for PWAs: (Round Table): Tuesday, July 21, 9:45 a.m. ù Tuberculosis and HIV: Plenary: Tuesday, July 21,11:30 a.m. ù Drug-resistant Tuberculosis: (Oral Abstract): Tuesday, July 21, 2:30 p.m. ù HIV Infection and TB: (Oral Abstract): Tuesday, July 21, 4:15 p.m. ù PCP Diagnosis, Therapy, and Prophylaxis: (Oral Abstract): Wednesday, July 22, 9:45 a.m. ù HIV Disease Progression, Co-Factors and Clinical Practice: Plenary: Wednesday, July 22,11:30 a.m. ù Diagnosis, Therapy, and Prophylaxis of Opportunistic Infections other than PCP: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù Major Opportunistic Infections: (Round Table): Wednesday, July 22, 4:15 p.m. ù Oral Manifestations: (Oral Abstract): Thursday, July 22, 9:45 a.m. ù Management of Malignancies: (Oral Abstract): Thursday, July 22, 2:30 p.m. Minicourses: ù Diagnosis and Management of Opportunistic Infections in Countries with Advanced Health Care Systems: Tuesday, July 21-Thursday, July 22, 6:00 p.m. ù Diagnosis and Management of Opportunistic Infections in Developing Countries: Tuesday, July 21-Thursday, July 22, 6:00 p.m. WOMEN AND HIV/AIDS ù Gender, Power, and HIV: (State-of-the-Art): Monday, July 20, 8:30 a.m. ù Gender-Related Variations in Natural History: (Oral Abstract): Monday, July 20, 9:45 a.m. ù Impact of HIV on Family Systems: (Oral Abstract): Monday, July 20, 2:30 p.m. ù Epidemiology of HIV in Women: (State-of-the-Art): Tuesday, July 21, 8:30 a.m. ù Human Sexuality: (State-of-the-Art): Tuesday, July 21, 8:30 a.m. ù AIDS Programs and Family Planning: (Round Table): Tuesday, July 21, 9:45 a.m. ù Definitions of AIDS: (Round Table): Tuesday, July 21, 9:45 a.m. ù AIDS and Breast Cancer: Lessons Shared: Tuesday, July 21, 9:45 a.m. ù Female Drug Injectors: (Poster Discussion): Tuesday, July 21,1:00 p.m. ù Clinical Manifestations of HIV in Women: (Oral Abstract): Tuesday, July 21, 2:30 p.m. ù Economic Impact on Households: Tuesday, July 21, 4:15 p.m. ù Variations in Clinical Manifestations by Population: (State-of-the-Art): Wednesday, July 22, 8:30 a.m. ù Prevention Programs for Women: (Round Table): Wednesday, July 22, 9:45 a.m. ù Decreasing Sexual Transmission in Women: (Poster Discussion): Wednesday, July 22,1:00 p.m. ù Women with HIV: Reproductive Choices: (Round Table): Wednesday, July 22, 4:15 p.m. ù Empowering Heterosexual Women: (Poster Discussion): Thursday, July 22,1:00 p.m. ù Empowerment of Women: (Round Table): Thursday, July 22, 4:15 p.m. ù Pelvic Inflammatory Disease: To be Scheduled. ù Intravaginal Barriers to HIV Transmission: To be Scheduled. GAY MEN AND HIV/AIDS ù Impact of High Mortality on Communities: (Poster Discussion): Monday, July 20,1:00 p.m. ù Evolution of Community-Based Organizations: (Oral Abstract): Monday, July 20, 4:15 p.m. ù Attitudes Toward Gay and Bisexual Men and Prevention Efficacy: Monday, July 20, 4:15 p.m. ù Human Sexuality: (State-of-the-Art): Tuesday, July 21, 8:30 a.m. ù Interventions for Men Who Have Sex with Men: (Poster Discussion): Tuesday, July 21,1:00 p.m. ù Maintaining Safe Behavior among Men Who Have Sex with Men: (Round Table): Tuesday, July 21, 2:30 p.m. ù Long-Term Survivors: (Round Table): Tuesday, July 21, 4:15 p.m. ù Homophobia, Denial and HIV Programs: (Round Table): To be Scheduled. ù Discordant Couples: (Oral Abstract): Wednesday, July 22, 2:15 p.m. ù Sustainable Community Action: Is It Possible? (State-of-the-Art): Thursday, July 22, 8:30 a.m. ù Human Rights Plenary: Thursday, July 22,11:30 a.m. ù Can Reinfection Occur? (Poster Discussion): Thursday, July 22,1:00 p.m. ù Approaches to AIDS Activism: (Round Table): Thursday, July 22, 2:30 p.m. ù Patterns & Structures of Male Homosexuality: (Round Table): Thursday, July 22, 4:15 p.m. YOUTH AND HIV/AIDS ù Impact of HIV on Family Systems: (Oral Abstract): Monday, July 20, 2:30 p.m. ù AIDS and Street Children in Brazil: (Case Study): Monday, July 20, 4:15 p.m. ù Safe Sex Programs for Youth: (Oral Abstract): Tuesday, July 21, 4:15 p.m. ù School-Based HIV Education: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù Youth and AIDS: Thursday, July 22, 9:45 a.m. ù AIDS and Adolescents: Thursday, July 22, 4:15 p.m. PEDIATRIC HIV/AIDS ù Management of Pediatric HIV: (Oral Abstract): Monday, 20, 9:45 a.m. ù Impact of HIV on Family Systems: (Oral Abstract): Monday, July 20, 2:30 p.m. ù Clinical Lessons - Pediatric Studies: (Special Presentation): Tuesday, July 21, 8:30 a.m. ù Pathogenesis in Pediatric Hosts: (Poster Discussion): Tuesday, July 12, lunch break ù Role of Breast Milk in Transmission: Wednesday, July 22: Lunch break ù Vertical Transmission: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù Maternal-Fetal Transmission: (State-of-the-Art): Thursday, July 23, 8:30 a.m. ù The Role of Breast Feeding in HIV Transmission: (Oral Abstract): Thursday, July 22, 9:45 a.m. ù Maternal-Infant Transmission by Population: (Poster Discussion): Thursday, July 23, Lunch break ù Early HIV Diagnosis in Infants: (Oral Abstract): Thursday, July 22, 4:15 p.m. Minicourses: ù Pediatric AIDS: Tuesday, July 21-Thursday, July 23, 6:00 p.m. PREVENTION Sexual Transmission ù Sex and Drugs in Prison: (Oral Abstract): Monday, July 20, 9:45 a.m. ù Interventions to Protect Sex Workers: (Poster Discussion): Monday, July 20, 1:00 p.m. ù Condom Use among Commercial Sex Workers and Their Clients: (Poster Discussion): Monday, July 20,1:00 p.m. ù Attitudes Toward Gay and Bisexual Men and Prevention Efficacy: Monday, July 20, 4:15 p.m. ù Interventions for Men Who Have Sex with Men: (Poster Discussion): Tuesday, July 21,1:00 p.m. ù Safe Sex Programs for Youth: (Oral Abstract): Tuesday, July 21, 4:15 p.m. ù Barriers to Condom Acceptance: (State-of-the-Art): Wednesday, July 22, 8:30 a.m. ù Decreasing Sexual Transmission in Women: (Poster Discussion): Wednesday, July 22,1:00 p.m. ù National Condom Prevention: Case Study: Wednesday, July 22, 4:15 p.m. ù Changing Male Heterosexual Attitudes & Behavior: (Oral Abstract): Thursday, July 22, 9:45 a.m. ù Determinants of Sexual Risk Behavior: (Oral Abstract): Thursday, July 22, 2:30 p.m. IVDU Transmission ù Sex and Drugs in Prison: (Oral Abstract): Monday, July 20, 9:45 a.m. ù Risk Behaviors among Drug Users: (Poster Discussion): Tuesday, July 21, 1:00 p.m. ù Female Drug Injectors: (Poster Discussion): Tuesday, July 21, 1:00 p.m. ù Human Rights and Drug Use: (Oral Abstract): Tuesday, July 21, 4:15 p.m. ù Interventions among IVDUs: (Poster Discussion): Wednesday, July 22, 1:00 p.m. ù Needle Exchange Programs: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù Transmission and Natural History of HIV Infection among IVDUs: (Oral Abstract): Thursday, July 22, 2:30 p.m. General ù Prevention Programs: (State-of-the-Art): Monday, July 20, 8:30 a.m. ù Costs and Benefits of Prevention Programs: (Poster Discussion): Monday, July 20, 1:00 p.m. ù HIV Transmission in Health Care: (Poster Discussion): Monday, July 20, 1:00 p.m. ù HIV Testing for Prevention: (Round Table): Monday, July 20, 2:30 p.m. ù Transmission of HIV through Blood and Blood Products: (Oral Abstract): Monday, July 20, 4:15 p.m. ù Infection Control in Health Care Settings: (Poster Discussion): Tuesday, July 21,1:00 p.m. ù Selecting and Evaluating Interventions: (Round Table): Tuesday, July 21, 2:30 p.m. ù Prevention Programs for Women: (Round Table): Wednesday, July 22, 9:45 a.m. ù Alcohol, Other Drugs, and Natural History of HIV: (Oral Abstract): Wednesday, July 22, 9:45 a.m. ù Prevention Efforts in the Workplace: (Poster Discussion): Wednesday, July 22, 1:00 p.m. ù School-Based HIV Education: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù Determinants of Risk-Taking Behavior: (State-of-the-Art): Thursday, July 22, 8:30 a.m. ù Evaluation of Prevention Programs: (Poster Discussion): Thursday, July 22, 1:00 p.m. ù HIV Transmission in Health Care: (Round Table): Thursday, July 22, 4:15 p.m. Minicourses: ù Selection and Evaluation of Interventions to Prevent HIV Infection: Tuesday, July 21-Thursday, July 22, 6:00 p.m. ù HIV/AIDS and the Commercial Sex Industry: Policy and Program Issues: Tuesday, July 21 - Thursday, July 22, 6:00 p.m. HIV/AIDS IN DEVELOPING COUNTRIES ù International Cooperation: (Round Table): Monday, July 20, 9:45 a.m. ù Modelling Impact on Health & Social Service Systems: (Poster Discussion): Monday, July 20, 1:00 p.m. ù Descriptive Epidemiology in Asia & Oceania: (Poster Discussion): Monday, July 20, 1:00 p.m. ù National Policies on International Mobility: (Round Table): Monday, July 20, 2:30 p.m. ù AIDS & Street Children in Brazil: (Case Study): Monday, July 20, 2:30 p.m. ù Developing Country STD Clinical Services: (State-of-the-Art): Tuesday, July 21, 8:30 a.m. ù Natural History of HIV-2: (State-of-the-Art): Tuesday, July 21, 8:30 a.m. ù Descriptive Epidemiology in Latin America and the Caribbean: (Poster Discussion): Tuesday, July 21, 1:00 p.m. ù Human Rights Violations: (Round Table): Tuesday, July 21, 2:30 p.m. ù STD Case Management in Developing Countries: (Round Table): Tuesday, July 21, 4:15 p.m. ù Variations in Clinical Manifestations by Population: (State-of-the-Art): Wednesday, July 22, 8:30 a.m. ù The United Nations and Global Responsibility: Wednesday, July 22, 9:45 a.m. ù Municipalities in the Developing World: (Round Table): Wednesday, July 22, 2:30 p.m. ù HIV/AIDS & Development Issues: Plenary: Wednesday, July 22, 11 :30 a.m. ù Clinical HIV Manifestations by Geographic Area and Ethnic Group: (Poster Discussion): Wednesday, July 22, 1:00 p.m. ù Transmission & Natural History of HIV: (Oral Abstract): Wednesday, July 22, 2:30 p.m. ù National Condom Prevention: Case Study: Wednesday, July 22, 4:15 p.m. ù Indigenous People and HIV/AIDS: Wednesday, July 22, 4:15 p.m. ù Socioeconomic Factors and HIV Spread: (State-of-the-Art): Thursday, July 22, 8:30 a.m. ù STD Diagnosis in Resource-Poor Settings: (State-of-the-Art): Thursday, July 22, 8:30 a.m. ù Human Rights: Plenary: Thursday, July 22,11:30 a.m. ù Descriptive Epidemiology in Africa: (Poster Discussion): Thursday, July 22, 1:00 p.m. ù Cultural Sensitivity in HIV Prevention: (Poster Discussion): Thursday, July 22, 1:00 p.m ù National Program Response to AIDS: (Oral Abstract): Thursday, July 22, 2:30 p.m. Minicourses: ù Diagnosis and Management of Opportunistic Infections in Developing Countries: Tuesday, July 21-Thursday, July 22, 6:00 p.m. ù International Cooperation and HIV/AIDS: Multilateral Organizations: Tuesday, July 21-Thursday, July 22, 6:00 p.m. ********** THE MINICOURSES As our knowledge of HIV/AIDS expands, it is critical that we put this knowledge to use as quickly and efficiently as possible. By examining how the recent research results and experience-based knowledge can be applied to various areas of endeavor, we can forge the essential link between raw data and the daily demands of the HIV/AIDS pandemic. To help address this need, the Harvard-Amsterdam Conference is inaugurating a series of minicourses designed to promote practical, accessible learning in fields ranging from clinical care to epidemiology to HIV/AIDS and the sex industry. The courses will combine didactic presentation With interactive discussion between participants nd presenters. Each minicourse will be held on three consecutive afternoons--Tuesday 21 July, Wednesday 22 July, and Thursday 23 July--from 6:00 to 7:30 p.m. Brief descriptions of each course are provided below. Diagnosis and Management of Opportunistic Infections For Countries with Advanced Health Care Infrastructures Coordinator: Judith Feinberg, M.D. The Johns Hopkins School of Medicine, Baltimore, Maryland, USA This minicourse is designed to present clinicians with the latest information regarding opportunistic infections. The course will focus on those opportunistic infections for which there have been the most significant advances in diagnosis, management or treatment in the last year. In anticipation of future problems, we will also address opportunistic infections which the most recent clinical/epidemiologic evidence indicates as of increasing incidence. Relying on brief presentations and extended case studies, experts will discuss the extent of specific diseases, state-of-the-art management, projected developments in the next year, and directions for future research and care. ********** Clinical Management of Persons with HIV Infection in Developing Countries Coordinator: Dr. Elly T. Katabira, Department of Medicine, Mulago Hospital, Kampala, Uganda In developing countries, clinical management of people with HIV/AIDS is hindered by the multiple obstacles of weak health care infrastructures, including limited financial resources, lack of adequate laboratory facilities and an insufficient supply of drugs. As a result of these factors, problems of clinical management in these settings may have a somewhat different focus than in industrialized countries. This minicourse is therefore specifically designed for clinicians providing care to persons with HIV/AIDS in developing countries. Using brief lectures, case studies and video presentations, the course will cover topics of central concern to developing country clinicians including: ù indications for HIV testing; ù pre-test and post-test counselling; ù initial evaluation and follow -up of persons with HIV infection; ù treatment of clinical manifestations including diarrhea, fever, cough, skin and neurological problems; ù clinical management of children with HIV infection. ********** Clinical Trials: Methods and Ethics Coordinator: Dr. Joep Lange, Director, National AIDS Therapy Evaluation Center, University of Amsterdam, The Netherlands The HIV/AIDS pandemic has focused unprecedented attention and controversy on the scientific methods and the ethics of clinical trials of drugs. This minicourse will analyze the central questions of clinical trials from the viewpoint of scientists, industry representatives, activists, and public officials, from both developing and industrialized nations. Issues to be considered in this minicourse range from the scientific and financial considerations that affect selection of drug candidates for clinical trials, to optimum selection and mix of clinical and laboratory endpoints, to ensuring effective patient involvement in trials. The applicability of clinical trial results to women and the need for clinical trials for alternative treatments will also be considered, and there will be an opportunity for participants to propose additional issues for discussion during the final session. ********** Pediatric HIV/AIDS Coordinator: Dr. Catherine Wilfert, Professor of Pediatrics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA With the burgeoning rate of HIV infection among children worldwide, interest in the complexity and challenges presented by pediatric HIV/AIDS has come of age. This minicourse will assess the most current information about HIV/AIDS in infants and children from epidemiological, diagnostic, and case management standpoints. The first session will present the most recent information about seroprevalance of HIV infection in women of child-bearing age and transmission rates from mothers to children. Projected infection rates among infants and women will also be discussed. The second session will focus on the diagnosis of infection in mothers and infants. Topics to be covered include: WHO clinical definition, availability and standardization of antibody testing, state of the art virus cultures, PCR determination and specific HIV IgA assessment. The third session will cover the management and care of infected children from nutrition and intravenous immunoglobulin to PCP prophylaxis and retroviral therapy. Existing clinical trials and vaccine possibilities will also be discussed. ********** Applying New Diagnostic Methods to Epidemiology Coordinators: Professor Francoise Brun-Viznet, Hopital Bichat Claude Bernard/Virology, Paris, France, and Dr. Phyllis Kanki, Harvard School of Public Health, Department of Cancer Biology, Boston, MA, USA In a global pandemic such as HIV/AIDS, epidemiological studies provide critical guidance for local, national, and global decision-making. These studies in turn are dependent upon accurate and economically feasible diagnostic methods. This minicourse will address this issue by attempting to answer the question: How can new techniques for diagnosis of HIV infection best be applied in epidemiological studies? Each of the three sessions will address a major topic in this area. The first session will discuss the latest advances in antibody testing, and how they might be employed for diagnosis in developing countries. The second will cover the diagnosis of HIV infection in newborns and children, and the use of prognostic markers in therapeutic trials. The final session will deal with techniques for quantification of HIV infection in therapeutic trials, paying special attention to plasma and cellular viremia as well as PCR techniques. ********** Epidemiological Methods of Surveillance and Prediction Coordinators: Dr. Victor De Gruttola, Harvard School of Public Health, Boston, MA, USA, and Dr. Noel Gill, PHLS AIDS Centre, Communicable Disease Surveillance Centre London, UK This minicourse will focus on the ways in which epidemiological studies can provide the optimum tools for planning strategies against HIV/AIDS. The course will examine the most effective epidemiological methods for predicting the future course of the HIV/AIDS epidemic and, through the use of case studies, will demonstrate the integration of surveillance methods with applied statistics. Specific topics to be covered include: ù estimating the AIDS incidence curve; ù estimating HIV prevalence and projecting AIDS incidence; ù HIV serosurveillance; ù estimating survival from surveillance data; ù reliability of AIDS reporting systems; and ù interpreting surveillance results and improving their utility. ********** Approaches to Selecting and Evaluating Interventions to Prevent HIV Infection Coordinator: Dr. Gary Slutkin, Chief, Office of Intervention Development and Support, Global Programme on AIDS, World Health Organization, Geneva, Switzerland This minicourse is intended for persons who are involved in policy, planning, implementation and/or evaluation of intervention strategies, whether in governmental or non-governmental agencies. Emphasizing work in developing countries, the course will describe the elements to be considered in all phases of creating and analyzing HIV intervention programs. To do so, the course will attempt to provide: ù an overview of interventions in use and their effectiveness; ù an analysis of criteria for selecting and prioritizing interventions, target audiences, and approaches; ù a framework for planning or adjusting a programmatic response to specific situations; ù case studies of successful programs; and ù an assessment of research and evaluation in programme development. ********** International Cooperation on AIDS Coordinator: Jeff O'Malley, Coordinator of Program Development, VIII International Conference on AIDS, Boston, MA, USA International cooperation programs can play a critical role in planning and carrying out global HIV/AIDS strategies, particularly in the developing world. In order for developing countries to take full advantage of this potential, however, they must be familiar with the programs potentially available to them. This minicourse is therefore conceived as an opportunity for Conference participants from developing countries to learn about the principal international cooperation programs. The course is organized as a series of three round table discussions focusing on multinational organizations, bilateral agencies, and non-governmental organizations. These discussions will be chaired respectively by As Sy (URES DAST MPE, Senegal), Anthony Klouda (International Planned Parenthood Federation, UK) and Jonathan Gates (InterCoalition on AIDS & Development, Canada). ********** HIV/AIDS and the Commercial Sex Industry Coordinator: Cheryl Overs, Network of Sexwork Related HIV/AIDS Projects, Paris, France This minicourse will explore a wide variety of approaches to supporting behavior change and/or to maintaining safe behavior among sex workers and their clients. It will also examine the ways in which law and public policy are applied to the sex industry, and the impact this has on HIV transmission among people who have sex in commercial settings. Finally, the course will assess the role in HIV prevention of policies and programs which aim to assist sex workers to discontinue sex work. ********** Alternative, Complementary and Traditional Therapies Coordinator: John S. James, Editor, AIDS Treatment News, San Francisco, CA, USA Around the world, approximately 75% of people with HIV/AIDS are using alternative, complementary and traditional therapies for HIV/AIDS. This minicourse is designed to provide information and stimulate discussion about these therapies and their relationship to Western therapies. The course will begin by describing treatments used in different regions through governmental and nongovernmental agencies. Next it will examine the issues arising in cross-cultural research and collaboration between Western and non-Western clinicians. Finally, the future place of controlled clinical trials as well as options for on-going communications among researchers will be discussed. In these discussions, specific attention will be given to: ù traditional African therapies; ù Chinese medical theory and treatments; ù nutrition and vitamin supplements; and ù naturopathic research. SATELLITE MEETINGS Below is a list of all presently scheduled satellite meetings of which we are aware. For general information, contact Ellen de Ranitz-Holdorp at the Dutch Foundation-AIDS Conference 1992, FAX 31.20.639.0156 A note on the program schedules: The program schedules presented in this preview are subject to change to meet changing demands. Inevitably, some schedules printed here will change by July 19. On arrival, please consult the official Conference Program for the most recent information on the dates and times for all conference activities. Commercial Satellite Meetings "HIV TREATMENT STRATEGIES FOR THE 1990s" The Wellcome Foundation Limited Sunday, 19 July, 1992 at 10.30 in Grote Zaal, RAI Center Contact: Caroline Gay, Wellcome Foundation Limited, Building 100B, Langley Court, Beckenham, Kent BR3 3BS, England . Phone 081-658-2211; fax 081-650-9862. "GASTROINTESTINAL DISORDERS IN HIV-INFECTED PATIENTS" Sandoz Pharmaceuticals Corporation Monday, 20 July, 1992 at 19.30 in Forum Zaal, RAI Center Contact: Tammy Altmark Audio Visual Marketing, Inc., 235 Park Avenue South, New York, NY 10003. Phone 212-6141370; fax 212-979-1214. "MANAGEMENT STRATEGIES FOR CYTOMEGALOVIRUS AND OTHER HERPESVIRUS INFECTIONS" Astra Pharmaceutical Products, Inc. Monday, 20 July 1992 at 19.30 in Grote Zaal, RAI Center Contact: Deborah Rachlin, Triclinica Communications, Inc. 425 West 59th Street, New York, NY 10019. Phone 212-6984084; fax 212-698-4003. "POLYMERASE CHAIN REACTION: DIAGNOSTIC KITS FOR HIV, MYCOBACTERIA AND THE IMPLICATIONS FOR DIAGNOSIS OF OPPORTUNISTIC INFECTIONS" Roche Molecular Systems Tuesday, 21 July 1992 at 19.30 in Midden Zaal, RAI Center Contact: Thomas H. Callaway, MD, Director of Scientific Affairs, Roche Molecular Systems, 1080 Route 202 South, Sommerville, NH 08876. Phone 919-361-7735; fax 919-3617797. "THE EVOLUTION OF COMMUNITY CARE" Caremark Tuesday, 21 July 1992 at 19.30 in Grote Zaal, RAI Center Contact: Dr. Patrick Rafferty, Wallingford Road, Compton, Newbury, Berkshire, UK. Phone 44-635-200-020; fax 44-635578-800. "THERAPEUTIC TREATMENT OF HIV PATIENTS: CLINICAL AND LABORATORY TOOLS" Bristol-Meyers Squibb Company Wednesday, 22 July 1992 at 19.30 in Grote Zaal, RAI Center Contact: Leif Anderson, Health Science Communications, 16 West 22nd Street, New York, NY 10010. Phone 212-727-1337; fax 212-727-2463. Non-Profit Satellite Meetings Women with HIV/AIDS - Workshop 14-17 July Anita Bolderhey, Dutch HIV Association (HIV VN), P.C. Hooftstraat 5, 1071 BL Amsterdam, 1071 BL Amsterdam, Postvus 15847,1001 NH Amsterdam, The Netherlands, tel. 31.20.66.44.076, fax. 31.20.66.689 Women's Meeting (for researchers, program workers, and seropositive women) 19 July, 12.30 - 15.00 Andita Bolderhey (see above) AIDS Documentation/Information Systems - Workshop 17 July Mary Hommes, National Committee on AIDS Control (NCAB), Polderweg 92, 1093 KP Amsterdam, The Netherlands, tel. 31.20.69.39.444, fax 31.20.69.27.989 AIDS en Drugs - Peer Pressure for Risk Reduction 20 July, 20.00 - 22.00 Wouter de Jong/Sam Friedman, NCAB (see above) Workstress and Burnout in Health Care Professionals Related to HIV/AIDS 22 July, 19.45 - 22.00 Emma van Dongen/Wiebe van der Woude, NCAB (see above) European Lesbian and Gay Psychologists 17 July, all day Jan Schippers, Schorer Foundation, P.C. Hooftsraat 5,1071 BL Amsterdam, The Netherlands, tel. 31.20.66.24.206, fax 31 .20.66.46.069 Network of Sexwork-related HIV/AIDS Projects 18 July, 10.00 - 18.00 Jan Visser, Mr. de Graaf Foundation, 4 Westermarkt, 1016 DK Amsterdam, the Netherlands, tel. 31.20.624.7149, fax. 31 .20.624.6529 Asian Solidarity Against AIDS - Workshop 19 July, morning I.S. Gilada, Indian Health Organization, H.Qs. J.J. Hospital, Bombay-400008, India, tel.91.22.851.9020, fax.91.22.851.9020 NARESA Meeting 20 July, evening Francesta Farmer, P.O. Box 53538, Nairobi, Kenya, te. 254.2.581.080 or 254.2.224.154 ICASO Latin America Meeting 20 July, evening Juan Jacobo Hernandez Chavez, Aptdo. Postal 13-320, Mexico D.F. 03500, Mexico, tel. 52.5.605.8299, fax 52.5.658.3534 ICASO Africa Meeting 20 July, evening As Sy Elhadj, 4 rue Kleber, Boite Postal 3370, Dakar, Senegal, tel.221.21.9695, fax. 221.222.695 ICASO Asia/Pacific Meeting 20 July, evening Hisham Hussein, P.O. Box 11859, 50760 Kuala Lumpur, Malaysia, tel. 60.3.282.1200 ext. 349, fax. 60.3.230.1640 ICASO Euro Meeting 20 July, evening Arne N. Husdal, P.B. 6879, St. Olavs Pl., 0130 Oslo, Norway, tel. 47.2.114.900, fax. 47.2.360.269 Indigenous Solidarity Against AIDS Meeting 21 July, 19.45 - 22.00 Ron Rowell, National Native American AIDS Prevention Center (NNAAPC), 5266 Boyd Avenue, Oakland, CA 94618, tel. 1.510.444.2051, fax 1.510.444.1593 ICASO General Meeting 21 July, evening Richard Burzynski, 30 Metcalfe, Suite 600, Ottawa, Canada KlP 5L4, tel. 1.613.230.3580, fax 1.613.563.4998 ICASO North America Meeting 20 July, evening Richard Burzynski (see above) International AIDS Society Gay and Lesbian Caucus To be announced Greg Herek, International AIDS Society (IAS), Department of Psychology, University of California, Davis, CA 95616 Culture, Sexual Behavior and AIDS Prevention 24-26 July Han ten Brummelhuis, AIDS and Anthropology Group, Department of Anthropology, University of Amsterdam, Oudezijds Achterburgwal 185, 1012 DK Amsterdam, The Netherlands, tel.31.20.525.2504, fax. 31.20.525.3010 HIV and Homosexuality - Workshops: 1. A Gay and Lesbian Preview of the VIII Conference on AIDS/III STD World Congress 20 July, 20.30 - 22.00 2. Towards and International Gay and Lesbian AIDS Policy 22 July, 20.30 - 22.00 3. HIV Policy, Prevention, Care, and Research: A Gay Perspective 23 July, 20.30 - 22.00 4. HIV Policy, Prevention, Care, and Research: A Lesbian Perspective 23 July, 20.30 - 22.00 Mart Simonse, Dutch Association for the Integration of Homosexuality - COC, rozenstraat 8, 1016 NK Amsterdam, tel. 31.20.62.34.596, fax. 31.20.62.67.795 AIDS and Primary Health Care: Implications for General Practice and Family Medicine 19 July, morning Mr. Ludwig Benecke, Benecke Consultants, Burgemeester Stramanweg 108,1011 AA Amsterdam, The Netherlands, tel. 31.20.69.66.349, fax. 31.20.69.18.446 Red Cross-Redcrescent AIDS Seminar 18 July, 10.00 - 18.00 19 July, 10.00 - 15.00 20 July, 18.30 - 21.00 24 July, 13.30 - 17.30 International Federation of Red Cross Redcrescent Societies, P.O. Box 372,1211 Geneva 19, Switzerland Symposium on Clinical Topics (and Nutrition) 25 July, 08.00 - 17.00 Mr. G. Nary, Physicians Association for AIDS Care (PAAC) 101 West Grand Avenue, Suite 200, Chicago, IL 60610, tel 1.312.222.1326. fax. 1.312.222.0329 Neurological and Neuropsychological Complications of HIV-Infection 14-17 July Dr. Peter Portegies, Academic Medical Centre (AMC), Clinica: AIDS Department, Meibergdreef 9,1105 AZ Amsterdam Zuidoost, The Netherlands, tel. 31.20.56.69.111, fax. 31.20.55.64.44~ HIV Infection: The Quality of Life and its Biopsychosocial Aspects 16-17 July Dr. S. Christopher W. Mead, Dr. Frits S.A.M., Netherlands Cancer Institute/WHO Quality of Life Centre, tel. 31.20.51.22.482. fax. 31.20.61.72.625 EEC-AIDS Task Force Program in Developing Countries 19 July, 12.00 - 16.00 Dr. Lieve Fransen, EEC Task Force, Rue Josef 1167, Brussels 1040. Belgium, tel. 32.2.231.1495, fax. 32.2.230.5574 HIV Nursing: Caring for the Future 19 July, 10.00 - 15.00 James Pl Halloran, Association of Nurses in AIDS Care, 704 Stony Hill Road, Suite 106, Yardley, PA 190678, tel. 1.215.321.2371, fax. 1.215.321.2370 General Meeting on Street Children 21 July, 20.00 - 22.00 Ana Filgueiras, SOS Crianca, Rua Barao de Jaguaribe 316, Apt. 201, CEP 22421, Rio de Janeiro, RJ Brazil, tel. and fax. 55.21.227.4029 Working Group: Street Children 22 July, 20.00 - 22.00 Ana Filgueiras (see above) Prof.Dr. I. Wolffers, Department of Social Medicine, Free University, Van der Boechorstrstraat 7,1081 BT Amsterdam, The Netherlands, tel. 31.20.5483366, fax. 31.20.6462228 The Nature of Buddy-Support as Voluntary Work 19 July, 10.00 - 15.00 Bouko Bakker, Buddy Project, Schorer Foundation, P.C. Hooftstraat 5, 1071 BL Amsterdam, The Netherlands, tel. 31.20.6624206, fax. 31.20.6646069 "Safe Not Sorry" and "Safe Sex and How to Get It" - Premier of 2 videos on assertion in preventing HIV infection in sexually active women 22 July, 19.45 - 22.00 Delys Sargeant, Social Biology Resources Centre, Melbourne, Victoria, Australia, tel.61.3.347.8700, fax. 61.3.347.5892 HIV Drug Resistance - Workshop 17-18 July The Conference Secretariat, International Clinical Forum Cosultants, Wicker House, 3 Liverpool Gardens, Worthing, West Sussex, BN11 lTF, United Kingdom, tel. 44.903.205213, fax. 44.903.210296 STD Diagnostics Initiative - Annual Meeting 16 July and 17 July Secretariat, STD Diagnostics Initiative, PATH, 4 Nickerson Street, Seattle, WA 98109, tel.1.206.285.3500, fax. 1 .206.285.6619 AIDS as a Development Program 19 July, 12.00 -14.00 Drugs and AIDS (in the Netherlands): Policy and Practice 21 July, 19.45 - 22.00 Ger Rolsma, Project AIDS and the use of Drugs, Dutch Institute for Alcohol and Drugs (NIAD), 6 St. Jacobsstraat, Postbus 725, 2500 AS Utrecht, The Netherlands, tel. 31.30.34.1200, fax. 31.30.31 .6362 Models of AIDS Prevention by Drugusers for Drugusers 22 July 19.45 - 22.00 Ger Rolsma, (see above) Talking About Risk (Strategies and techniques to help drugusers) 23 July, 19.45 - 22.00 Ger Rolsma, (see above) Empowering People with HIV/AIDS for Self-Advocacy in Developing Countries 22 July, 20.00 - 22.00 Euthenasia, Medical, Ethical and Legal Issues - Workshop 29 July Rob Tielman/Jean Davies (see above) Endpoints in HIV Clinical Trials 18 July, 14.00 - 18.00 Dr. J.A.M. Lange, National AIDS Therapy Evaluation Centre (NATEC), Academic Medical Centre, University of Amsterdam, Meibergdreef 9,1105 AZ Amsterdam, The Netherlands, tel. 31.20.566.43.80/4479, fax 31.20.691.88.21 Slide Seminar in Oral Pathology 24-25 July Mrs. D. Chevalking, Congress Secretariat Oral Pathology, Free University Hospital, Department of Oral Pathology, 117 Boelslaan, 1081 HV Amsterdam, The Netherlands, tel. 31.29.548.2306, fax. 31.20.548.5226 PRIORITY QUESTIONS FOR THE HARVARD/AMSTERDAM CONFERENCE Marcus Conant is Clinical Professor of Dermatology at UCSF and an internationally recognized expert on Kaposi's sarcoma . He also cares for patients at his general medicine and HIV disease clinic in San Francisco. In April 1992 a group of clinicians, investigators and caregivers met in New York City to identify major areas of concern and as yet unresolved issues in the management of HIV disease. These concerns and issues will be communicated to abstract and poster presenters at the Harvard-Amsterdam Conference on AIDS and to an expert panel that will discuss the clinically relevant issues on July 24, the last day of the Conference. Their answers will be printed and distributed to interested patients, physicians and other caregivers. We have divided the unresolved issues into 3 sections. The first group, published below, contains the questions we believe can be answered by mid-1992. These priority questions, if answered, would immediately and significantly improve the quality of care provided to individuals with HIV disease. Section 2 contains questions about areas of ongoing research. These are issues that may be resolved in 1993, and therefore will have an impact next year. Section 3 contains issues in vital areas that should be addressed by future research and clinical trials. The answers to these fundamental questions may lead to a cure for HIV disease. Marcus Conant, MD BETA will publish an edited transcript of the panel's findings in the August 1992 issue. -Editor Priority Questions 1. What is the value of surrogate markers to evaluate disease progression? 2. Which markers, if any, can be used clinically to determine when to intervene in different ways? 3. How do we explain long-term survivors of HIV disease? 4. What is the risk of oral transmission of HIV? 5. What is the real frequency of heterosexual transmission of HIV disease in the U.S.? 6. What is the relationship of disease progression to viral burden? Is there a difference in virulence among different HIV strains? 7. What role does monitoring P24 antigen or antibody have in predicting disease outcome? 8. What role does monitoring beta-2 microglobulin or neoptrin have on predicting disease outcome? 9. When should you use PCR to diagnose HIV infection? 10. What effect does travel, ultra violet light, pets and other environmental exposures have on the natural history of HIV disease? 11. What is the risk of healthcare workers getting TB? 12. Can you describe any new HIV-associated diseases? 13. What are the immunosuppressive effects, if any, of methadone and other opiate narcotics? 14. What is the clinical significance of in vitro sensitivity to AZT after 3 to 5 years of therapy? 15. How does AZT compare to ddI in terms of effectiveness, proven clinical benefits, effect on surrogate markers and toxicity? 16. How and when do you use AZT and ddI together? 17. How do you define AZT failure? 18. What is the state-of-the-art for antiretroviral therapy? a. When to initiate therapy and with what drug? b. When to change drug? c. When do you add drugs? d. What drugs should be added? 19.Should we be treating patients during acute infection with antiretroviral therapy? 20. How do we optimize therapy with the drugs we have now in terms of therapy and prophylaxis? 21. What is the correct dose of AZT? 22. What is the correct dose of ddI? 23. What is the correct dose of ddC? 24. Which antiretrovirals should be combined? At what dose? When? 25.How should antiretrovirals be combined - concomitantly or sequentially? 26. Which antiretrovirals and at what dosage should be used in patients with HIV-associated central nervous system disease? 27.Is there cross resistance among nucleoside RT inhibitors? 28. Does AZT have effects other than its direct effect on CD4 counts? 29. Do ddI and ddC increase immune function in the same manner as AZT? 30. What is the current management of AZT-induced headache, nausea, anemia, neutropenia and myopathy? 31. What is the current management of ddI-induced pancreatitis and neuropathy? 32. What is the current management of ddC-induced neuropathy? 33. Are ddI or ddC effective in the management of ITP and/or psoriasis? 34. What is known about the beneficial effects, if any, of combining AZT and acyclovir? 35. What is known about the clinical effects of initiating AZT in HIV positive patients with CD4 counts above 500/mm3? 36. What has been learned about the combination of AZT and interferon? 37. Have any new AZT toxicities been identified? 38. How effective is AZT at a dose of 300 mg/day compared to AZT at a dose of 600 mg/day? 39. Can AZT be used in combination with DHPG [ganciclovir]? If so, when and at what dose? 40. What effects do diet, alcohol and / or drugs have on the uptake and pharmacology of AZT? Of ddI? Of ddC? 41.What drugs interact adversely with AZT? 42. What drugs interact adversely with ddI? 43.What drugs interact adversely with ddC? 44. What effect does AZT have on survival? 45. What is known about the clinical effectiveness of AZT in people of color, Hispanics, women, children and other populations? 46. Should the dose of AZT or any other antiretroviral be increased in patients with increased viral burden? 47.What data do we have on the effect of AZT on surrogate markers of disease progression? 48. Is there any further information on the emergence of acyclovir resistant herpes virus? 49. Is there any evidence that gp120 or other vaccines stabilize CD4 counts in HIV-infected patients? 50. What is the varying response to vaccines with progression and with declining CD4 levels? When should booster shots be given? What dose of booster shots should be used with varying CD4 levels? "These priority questions, if answered, would immediately and significantly improve the quality of care provided to individuals with HIV disease." 51.What data was presented or is available on the efficacy of Foscarnet, N-butyl DNJ, Interferon, Protease Inhibitors, Non-Nucleoside RT Inhibitors, compound Q, Photopherisis, Ribavarin, Isoprinosine, Immuthiol, D4T, Peptide-T, Cimetidine? 52. What data, if any, was presented on the beneficial effects of TP-5, thymosine, PCM-4, CD4-IGG, IL2? 53. What is the best treatment of and prophylaxis for MAI? 54. What is the best treatment of and prophylaxis for CMV. 55. What is the best treatment of and prophylaxis for cryptosporidiosis? 56. What is the state-of-the-art of the diagnosis, therapy and prophylaxis of tuberculosis in the patient with HIV disease? Does it differ in the western world and in the third world? 57. Is there any new treatment for PML? 58. What is the etiology of Kaposi's sarcoma? 59. Was beneficial effect on disease progression shown with exercise, vitamins, diet, nutrition, TPN, acupuncture, coenzyme Q, appetite stimulants, meditation, iscador, ozone, hypericin, aloe vera, aspirin, fish oils, antibuse? 60. What have we learned this year about aspergillus? 61. What have we learned about the diagnosis and therapy of histoplasmosis? 62. What have we learned about bacterial pneumonia? 63. What have we learned this year about coccidiomycosis? 64. What dose of pyrimethamine should be used for prophylaxis of toxoplasmosis? 65. What is the appropriate maintenance therapy for someone recovering from toxoplasmosis? 66. At what CD4 count should prophylaxis for cryptococcal meningitis be initiated? With what drug or drugs? 67. What is the most appropriate treatment for cryptococcal meningitis? 68. What is the incidence of fluconazole resistance in patients: a. treated for acute cryptococcal meningitis? b. receiving prophylaxis for cryptococcal meningitis? 69. What is the incidence of resistant candida to fluconazole? 70.What was presented on a new urine diagnostic test for microsporidium? 71. What was presented on new treatments for microsporidium? 72. Is there any effective prophylaxis for cryptosporidiosis? 73. Are there any beneficial effects from treating cryptosporidiosis with humatin, colostrum, somatostatin, azithromycin and / or leftrazoril? 74. What is the algorithm for the diagnosis of HIV-associated esophageal ulceration? 75. What is the best treatment for esophageal ulceration? 76. Is there any further information on foscarnet versus DHPG in the treatment of CMV? 77. What data was presented on resistance of CMV to DHPG? 78. What new treatments for CMV were discussed? 79. Should laser surgery be used to prevent retinal detachment patients with CMV retinitis? 80. What is the best way to diagnose MAI? 81. What is the current standard of care for MAI? 82. What has been the impact of colony stimulating factors on the treatment of lymphomas? 83. What is the natural history of HIV-associated sinusitis? 84. Are there any new treatments for: a. molluscum contagiosum? b. eosinophilic folliculitis? c. pruritus? d. xerosis? 85. Are there any new HIV-associated oral manifestations? 86. Are there any new treatment for HIV-associated oral manifestations? 87. What is the most effective therapy for HIV positive individuals with vaginal or rectal warts? 88. Is there any information about the natural history of HIV disease in women, people of color, injecting drug users, adolescents, children? 89. How do yo confirm HIV disease in an infant? 90. What are the unique clinical presentations of HIV disease in women? 91. What antiretroviral therapy and at what dose should be used in women? 92. What is the appropriate management of the HIV positive pregnant patient? 93. What are the most effective behavior modification techniques? 94. Have there been any recent changes in pre- and post-test counseling recommendations? What impact does learning about a positive test have on an individual's CD4 count? 95.Do any psychosocial interventions work to prevent disease progression? 96. What has been learned about the integration of HIV care in STD clinics, in methadone maintenance clinics, in childcare centers? ********** PREVENTIVE TREATMENT REGIMENS FOR OPPORTUNISTIC INFECTIONS OTHER THAN PCP Note: The preventive treatment regimens outlined here have not been tested and proven safe and effective in clinical trials, with the exception of acyclovir to prevent recurrent herpes simplex and isoniazid to prevent reactivation of tuberculosis. INDICATION DRUG DOSE recurrent oral herpes (HSV-1); acyclovir 400 mg twice a day recurrent genital/anal herpes (HSV-2) tuberculosis isoniazid 300 mg/day for 9 to 12 months fungal infections fluconazole 100 mg/day toxoplasmosis pyrimethamine 25 mg/day or 50 mg 3 times a week or azithromycin 500 mg once a day or TMP-SMX 1 double-strength (Bactrim, Septra) tablet a day cytomegalovirus infection acyclovir 1-4 grams a day or intravenous 250 mg IV daily ganciclovir body for 14 days, then weight 120 lbs or weekly less body weight more 50 mg IV daily for than 120 lbs 14 days, then weekly MAC rifabutin 300 mg/day or ciprofloxacin 500 mg once a day or clarithromycin 500 mg/day or azithromycin 500 mg/day or clarithromycin same dose as single- plus ciprofloxacin agent therapy or azithromycin ********** RESEARCH NOTES Ronald A. Baker, Ph.D. Ronald Baker is editor of BETA and coauthor of Early Care for HIV Disease (2nd revised edition), a book for people living with HIV infection. NEW STUDIES ON KAPOSI'S SARCOMA (KS) A KS Link to Human Papillomavirus Most epidemiologists believe that an infectious agent other than or in addition to HIV causes AIDS-associated KS. In February, the British medical journal The Lancet published a paper by virologist and dermatologist Alvin Friedman-Kien suggesting that human papillomavirus (HPV) is the cause of KS. HPV has already been identified as the cause of genital warts, cervical cancer and, possibly, anal cancer among HIV positive men. Dr. Friedman-Kien and colleagues used the sensitive polymerase chain reaction (PCR) test to show that DNA resembling HPV-16 DNA was present in cells taken from KS lesions and in KS cells grown in the laboratory. Although the published study identified only a low percentage (15%) of KS cells infected with HPV16, Dr. Friedman-Kien says he has since detected HPV-16 in about 95% of tested cells. The notion that HPV causes KS has been met with skepticism by some researchers. Joel Palefsky of UCSF says he has been testing KS lesions for the presence of HPV and has not found it. William Blattner of the National Cancer Institute believes an as yet unidentified retrovirus is the cause of KS. Valerie Beral of Oxford published a paper in the March issue of The Lancet suggesting that KS is most common among HIV positive gay men who have had oral-fecal contact through "rimming." This notion challenges the KS-HPV connection, because papillomaviruses are transmitted by genital to genital sexual contact. Dr. Beral also notes that her oral-fecal contact theory helps to explain why KS is endemic among heterosexual men and women in Africa, where poor hygiene rather than sexual contact may be the cause of fecal exchange. "The researchers believe that direct or indirect inhibition of the production of oncostatin M could slow or stop the progression of KS. The Tat gene of HIV, for example, may increase oncostatin M production in the body." Oncostatin M: A Major Growth Factor for KS Researchers have identified the cytokine oncostatin M as a major growth factor for AIDS-associated KS. Cytokines are proteins produced by white blood cells that act as chemical messengers between cells. Cytokines such as interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor and gamma interferon have all been shown to stimulate the growth of KS cells in laboratory studies. Oncostatin M is a cytokine produced by activated white blood cells (T-lymphocytes) that increases the expression of Interleukin-6 in cultures of human blood cells. KS cell lines grow and proliferate readily when oncostatin M is added to the culture. These findings suggest that this cytokine may play a key role in the development and progression of KS in humans. The researchers believe that direct or indirect inhibition of the production of oncostatin M could slow or stop the progression of KS. The Tat gene of HIV, for example, may increase oncostatin M production in the body. A new Hoffmann-LaRoche drug now entering human testing, the Tat gene inhibitor, may have a future role in AIDS-KS therapy through its ability to inhibit production of the Tat ~ene of HIV. SP-PG:A Promising Anti-KS Drug The angiostatic compound SP-PG, a naturally-occurring sulfated polysaccharide, can control the growth of AIDS-associated KS cells in laboratory studies of mice, according to researchers at the National Cancer Institute. A paper published in the March 1992 issue of Science confirms promising reports of this new drug that have appeared in earlier issues of BETA. SP-PG has been tested in mice with and without the addition of oral hydrocortisone. At a dose of 250 mg/kg of body weight, SP-PG completely inhibited the blood vessel proliferation characteristic of AIDS-associated KS. When researchers combined SP-PG with hydrocortisone, the effect of prohibiting blood vessel growth and formation of KS lesions was even stronger. These study results suggest that SP-PG may limit the growth and development of KS lesions in humans. SP-PG also appears to be non-toxic, unlike other angiogenesis inhibitors such as protamine sulfate or heparin, which have shown toxicity or caused bleeding. SP-PG is manufactured by Daiichi Pharmaceutical Company of Tokyo. Daiichi is supplying SP-PG to the National Cancer Institute for use in future animal and human testing. Rifabutin:A Successful Prophylaxis for MAC A recent study, unpublished at press time, shows that the experimental antibiotic rifabutin can reduce by nearly 50% the rate at which people with AIDS develop MAC (Mycobacterium avium complex). About 25% of all people with AIDS ultimately develop symptomatic MAC, a disease that causes severe weight loss, fatigue, diarrhea and fever. Symptomatic MAC disease occurs most frequently in individuals with fewer than 50 T-helper cells. Treatment with standard antibiotic regimens often has failed to control the disease, and relapse is common. Investigators have been studying several new drugs both as prophylactic agents and as treatments for acute disease. "The experimental antibiotic rifabutin can reduce by nearly 50% the rate at which people with AIDS develop MAC (Mycobacterium avium complex)." Rifabutin is now available to people with advanced HIV disease through an FDA-approved Treatment Investigation New Drug program (Treatment IND). The drug's manufacturer, Adria Laboratories, expects to enroll up to 5,000 people with AIDS through the rifabutin expanded access program. To be eligible for the drug through this program, individuals must have an AIDS diagnosis, no previous history of MAC and a T-helper count of 200 or less. For more information about enrollment, physicians may call Adria at 800-552-7228. To prevent the onset of MAC, individuals in the trial took 150 mg rifabutin twice a day. The most serious potential side effect of rifabutin is neutropenia, an abnormally low number of white blood cells. Fortunately, few people in this study of 590 patients had to stop the drug for this reason. Researchers are experimenting with a variety of drugs both as single agents and in combination to prevent and to treat MAC, including ciprofloxacin, clarithromycin, azithromycin and TLC G-65, a liposomal antibiotic. Clarithromycin as Prophylaxis for MAC The ACTG placebo-controlled study of clarithromycin (Biaxin) as prophylaxis for MAC has been cancelled. When results of the rifabutin study surfaced (see above), investigators decided they could not ethically conduct any MAC trial using a placebo. There are preliminary plans for a redesigned ACTG trial comparing rifabutin to azithromycin (Zithromax) and clarithromycin, and possibly a clarithromycin/rifabutin combination prophylaxis trial for MAC. Meanwhile, Abbott Laboratories, manufacturer of clarithromycin, is actively recruiting for a dose-ranging study comparing 500 mg/day and 1,000 mg/day clarithromycin. To be eligible, HIV positive individuals must have fewer than 100 T-helper cells and no previous history of MAC. Physicians may call Abbott for more information (800-688-9118). The Collector: A Novel Therapy The Collector (a.k.a. Micro CELLectorTM ) is the name given to a device for treating disease by manipulating blood cells outside the body and returning the treated blood to the patient. As an AIDS treatment, the Collector is used to harvest CD8 cells from the patients' blood. CD8 cells appear to be responsible for keeping HIV in check during the so-called "latency period" of HIV infection. After recovering the CD8 cells from the body, they are multiplied and activated by treatment with the cytokine interleukin-2. "The treated CD8 cells are infused into the patient in an attempt to improve the body's immune response against HIV and related infections and malignancies." The goal of the therapy is to reactivate the individual's CD8 cells that normally fight disease, but that have become dysfunctional as a result of HIV disease progression. The treated CD8 cells are infused into the patient in an attempt to improve the body's immune response against HIV and related infections and malignancies. In Phase I safety trials, the Collector has shown little toxicity, except for a reversible nausea in some patients. Dr. Ronald Harderman, Director of the Pittsburgh Cancer Institute, said the reinfused, treated CD8 cells showed the ability to kill HIV in virtually all patients treated. Phase II trials to evaluate the effectiveness of the Collector are planned for the second quarter of 1992 in the San Francisco Bay area. Applied Immune Sciences, Inc. has entered into a joint venture with Caremark, an affiliate of the Baxter Healthcare Corporation, to develop and operate Collector therapy centers. The San Francisco center will be one of the clinical trials sites in a multicenter Phase I / II study required for FDA approval. Negotiations have begun to start a trial at San Francisco General Hospital among people with KS, since some KS patients have shown improvement in their lesions after using the therapy. Dr. Thomas B. Okarma, president of Applied Immune Sciences, said the Collector cannot cure AIDS, but the treatment may suppress HIV growth sufficiently to allow individuals to live a normal lifespan. Repeated treatments would probably be necessary. The Collector will likely be an expensive anti-HIV therapy. TWO STUDIES REPORT ON EARLY AZT TREATMENT AND SURVIVAL Numerous studies have demonstrated a clear survival benefit from AZT use among people with advanced HIV disease. An important question to answer is whether AZT can increase survival rates among people who take the drug early, before they develop AIDS. Two recently published studies have addressed this question, and each draws a different conclusion . Both studies are summarized below. The Veterans Affairs (VA) Cooperative Study AZT at 1500 mg/day does not improve survival among; people who begin the drug early (200-500 T-helper cells), according to results of a trial at Veterans Affairs medical centers in 8 cities. The Veterans Affairs report, published in a recent issue of the New England Journal of Medicine, focuses on the lack of survival difference between patients who started AZT at the 500 T-helper cell level compared to those who started when their T-helper counts fell to below 200. The researchers found survival rates the same in both groups, even though people in the early AZT treatment group experienced a 50% reduction in disease progression and a significant increase in T-helper cells over those individuals who started AZT later. The researchers also noted that once AIDS developed in the individuals on early AZT therapy, more of them developed multiple AIDS-defining infections and malignancies, and more died than those who took AZT later. "AZT at 1500 mg/day does not improve survival among people who begin the drug early (200-500 T-helper cells), according to results of a trial at Veterans Affairs medical centers in 8 cities." If these results are accurate, they call into question whether T-helper cell count and disease progression are reliable markers for survival. These survival data came from the same Veterans Affairs study that found that African Americans and Hispanics benefitted less from AZT treatment than Caucasians. More recent studies designed specifically to test this finding have shown no difference in responses to AZT treatment among these racial groups. As a result, some researchers have questioned the validity of the VA study's survival data. Others have noted that the dose of AZT used in the Veterans Affairs study (1,500 mg/ day) is 3 times the currently-recommended dose (500-600 mg/day). The unusually high dose of AZT used may have adversely affected survival in both treatment groups. "A new study of over 2,500 men . . . indicates that early AZT treatment can significantly prolong survival." The Multicenter AIDS Cohort Study (MACS) A new study of over 2,500 men published in the New England Journal of Medicine indicates that early AZT treatment can significantly prolong survival. The investigators say their study detected a significant survival benefit from early AZT use because of its large size. The Veterans Affairs study (see above), which analyzed only 43 deaths, was too small to show this effect, according to the MAC researchers. The significantly larger MAC study analyzed data from 306 deaths. After 6 months of medical followup in the MAC study, there were 57% fewer deaths among the men who received early AZT treatment, 46% fewer deaths at 12 months, 41% fewer at 18 months and 33% fewer at 24 months. Early AZT therapy with use of PCP prophylaxis contributed to an additional survival benefit. The results of the MAC study support the notion that early AZT treatment and PCP prophylaxis not only slow progression to AIDS, but also increase survival time, according to the authors. "In general," said investigator Dr. Neil Graham at the Johns Hopkins School of Public Health, "men starting with 200-349 T-helper cells benefitted the most from treatment with AZT. A longer follow-up period will be needed before we can accurately measure a significant therapeutic effect for people with T-helper counts greater than 350." Fluconazole as First-Line Treatment for Cryptococcal Meningitis Oral fluconazole (Diflucan) is far less toxic and only slightly less effective than intravenous amphotericin B treatment for cryptococcal meningitis (CM), according to a NIAID study. Treatment was successful in 25 of 63 individuals (40%) using amphotericin B and in 44 of 131 (34~c) taking fluconazole. The authors conclude that there was no significant difference in efficacy between the 2 drugs, and further, that fluconazole is an acceptable alternative to amphotericin B as a first-line treatment for acute CM. Study participants tolerated fluconazole significantly better than amphotericin B: 27% of those using fluconazole reported adverse side affects, primarily nausea, compared to 64% of those on amphotericin B. Eight percent of the amphotericin B patients experienced severe toxicity necessitating discontinuation of treatment, compared to 2% of fluconazole. "Oral fluconazole (Diflucan) is far less toxic and only slightly less effective than intravenous amphotericin B treatment for cryptococcal meningitis (CM), according to a NIAID study." The authors noted that "single drug therapy with either drug is most effective in patients who are at low risk for treatment failure." Normal mental status and a CM antigen titer level below 1:1024 are pretreatment factors associated with a low risk of treatment failure. Sixty-two percent of the study group were low risk. Earlier studies have shown oral fluconazole the preferred drug for maintenance therapy following successful treatment with amphotericin B for the initial CM infection. Fluconazole is also used to treat severe candida infections. The authors point out that this study leaves several important questions unanswered: what is the preferred treatment for people with high risk of treatment failure? Can outcomes be improved with higher doses of either drug? What is the optimal timing for switching from intravenous amphotericin B to oral fluconazole among people at high risk for treatment failure? How effective is the antifungal drug intraconazole compared to fluconazole? New Data on Passive Hyperimmune Therapy HemaCare Corporation, a small Los Angeles-based blood products company, claims beneficial results for people with AIDS and severe ARC who have used its plasma treatment for 6 months. The company says that preliminary data from its 1-year study of passive hyperimmune therapy (PHT) suggests the treatment may improve survival and reduce the incidence of AIDS-related opportunistic infections. Dr. Joshua Levy, medical director of HemaCare, said early data showed significant increases in T-helper counts and significant decreases in beta-2 microglobulin levels in people taking a full dose of plasma (500 cc once monthly) compared to those on placebo. The treatment appears to cause only minor side effects. No supporting data were released by the company, and the findings have not been published. PHT involves taking blood plasma from healthy, HIV positive donors with high level of HIV neutralizing antibodies. The donated plasma is treated to kill any harmful organisms (such as HIV or hepatitis B). The treated plasma is then re-infused into people with AIDS, in the hope that the anti-HIV antibodies will improve their clinical status. The ongoing HemaCare study involves| 219 volunteers taking either a full dose of treated plasma, half dose or placebo. HemaCare Corporation has an exclusive license from Medicorp, Inc., holder of the patent for PHT, to test and commercialize PHT in the state of California. Because the HemaCare product is produced exclusively within California, state law permits the California Food and Drug Branch (FDB) to approve use of the treatment without FDA sanction. If the California FDB approves, HemaCare plans to distribute the plasma treatment to 1,000 people as part of an expanded access program. Individuals receiving the treatment (but not plasma donors) would have to pay for at least part of the cost of the therapy. HemaCare did not speculate on the dollar| amount required to cover treatment costs for 1,000 people. HemaCare Corporation has an exclusive license from Medicorp, Inc., holder of the patent for PHT, to test and commercialize PHT in the state of California. AZT Plus Intravenous Immunoglobulins (IVIG) A treatment regimen that combines AZT (500 mg/day) and intravenous immunoglobulins (600 mg/ kg of body weight every 4 weeks) may give greater protection against opportunistic infections and preserve platelet counts better than use of AZT alone, according to Italian researchers. The 15 patients in the Italian study taking AZT plus IVIG experienced no additional toxicities. Although IVIG therapy is expensive, the authors point out that the expense may be compensated for by reducing hospital stays and the reduced necessity of using drugs against opportunistic infections. Several brans of IVIG are available, including Sandosglobulin, used by the Italian researchers. Treatments for Peripheral Neuropathy (PN) Symptoms of peripheral neuropathy (PN) are common among HIV positive individuals. PN may result from HIV infection itself or possibly as a side effect from use of such drugs as ddI, ddC, dapsone or isoniazid. Symptoms may be mild or severe, and may be chronically or only intermittently present. Symptoms typically include pain, burning, tingling or numbness in the feet and / or hands. In some cases, patients may have difficulty walking, and in severe cases, paralysis may result. PN that results from drug use is usually reversible once the drug is discontinued. There is no known treatment for the cause of HIV-associated PN, but several drugs approved for other indications may relieve symptoms. Perhaps the most frequently prescribed drug for symptomatic relief from PN is amitriptyline (Elavil, etc.) at a dose of 50-150 mg/day, taken at bedtime. Other tricyclic antidepressants have also been used successfully to relieve PN symptoms. More recently, researchers have reported positive results from the use of the drug Mexitil (10 mg/kg day), an FDA-approved anti-arrhythmic drug. Individuals who do not respond to these drugs, or who are experiencing severe pain, may benefit from the anti-convulsant carbamazepine (Tegretol) and also from analgesics, such as Tylenol with codeine. "Perhaps the most frequently prescribed drug for symptomatic relief from PN is amitriptyline (Elavil, etc.) at a dose of 50-150 mg/day, taken at bedtime." Greek researchers report that regular, long-term use of the B vitamin biotin has been effective for PN in diabetics. Patients in a small study taking biotin showed improvement in tests of nerve conduction within 48 weeks after starting the vitamin. Biotin was administered in the following regimens in the Greek study: 10 mg/day injected intramuscularly (IM) for 6 weeks, then 10 mg/day IM 3 times a week for 6 weeks, then 5 mg/day orally for up to 2 years. The optimal dose of biotin as a treatment for PN is unknown. Because of its low toxicity profile, patients may want to try it in doses of 5-1Omg/day orally before taking other agents with more pronounced side effects. Drugs used in the treatment of HIV disease that may cause PN include ddI and ddC (for HIV infection), dapsone (for PCP prophylaxis), ethambutol and isoniazid (for tuberculosis), and lithium (for AIDS-related dementia). High doses of vitamin B6 may also induce symptoms of PN. No Benefit Shown from Use of Oral Interferon The drug Kemron, a chewable wafer form of alpha interferon, as well as other forms of low dose alpha interferon, do not confer clinical benefit, according to a new government report from the NIAID. The NIAID report, commissioned by the AIDS Research Advisory Committee, summarizes 13 studies of low dose alpha interferon. Although the report is preliminary and as yet unpublished, it appears that the strikingly promising results of the 1990 African study by Dr. Davy Koech have not been substantiated by other researchers. Dr. Koech reported that his patients using low dose alpha interferon experienced significant increases in T-helper cells, elimination of disease symptoms and even a conversion from HIV positive to HIV negative. German, American and Canadian studies do not support these findings. The AIDS Research Advisory Committee has recommended that the new report be widely communicated, and that HIV positive individuals use therapies that have been shown effective. Anergy and Testing for Tuberculosis Many individuals with HIV infection, particularly those with fewer than 500 T-helper cells, will test negative on the PPD test, the standard screening test for infection with M. tuberculosis, even though they have been infected with the organism. This may occur because these individuals are anergic. This means their immune systems cannot mount an observable immune response to infection with M. tuberculosis. "To determine whether or not an individual is anergic, physicians use simple skin tests for candida, mumps or tetanus toxoid as companion tests with the PPD." To determine whether or not an individual is anergic, physicians use simple skin tests for candida, mumps or tetanus toxoid as companion tests with the PPD. If the tested individuals shows no reaction to these antigens, he/she is considered anergic, and probably will not have a positive response to the PPD Tb test, even if infected with M. tuberculosis. Anergic individuals should have regular chest x-ray screening (every 6 months) and should be closely monitored by their physician for symptoms of Tb. People at high risk for infection with M. tuberculosis may want to consider preventive treatment with the anti-Tb drug isoniazid (300mg/day for 9-12 months). For more information, see the cover article on tuberculosis in the February 1992 issue of BETA. Selected Sources Advisory committee recommends approval of ddC as combination AIDS therapy. Talk Paper from the Food and Drug Administration Press Office. April 21, 1992. Altman L. No benefit seen in use of interferon in AIDS. The New York Times. April 28, 1992. B-6. De Simone C et al. Clinical and immunologic effects of combination therapy with intravenous immunoglobulins and AZT in HIV-infected patients. Immunopharmacology and Immunotoxicology 13(3):447-458, 1991. Fisher L. Immune cell modification outside the body. The New York Times. January 22, 1992. Graham N. The effects on survival of early treatment of human immuno- deficiency virus infection. The New England Journal of Medicine 326(16):1037-1042, April 16, 1992. Hamilton J et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. The New England Journal of Medicine 326(7):437-486, February 13, 1992. HemaCare announces promising interim results from clinical trial of potential new AIDS treatment. News release from HemaCare Corporation . Miles S et al. Oncostatin M as a potent mitogen for AIDS-related Kaposi's sarcoma-derived cells. Science 225(5050):1430-1432, March 13, 1992. The NIAID report on use of low-dose oral IFN-a [alpha interferon]. Executive Summary. Department of Health and Human Services. April 1992. Nair B et al. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science 225(5050):1430-1432, March 13, 1992. Nakamura S et al. Inhibition of development of Kaposi's sarcoma-related lesions by a bacterial cell wall complex. Science 225(5050):1437-1440. March 13, 1992. Palca, J. Kaposi's sarcoma gives on key fronts (Editorial). Science 225(5050):1352-1354, March 13, 1992. Rifabutin treatment IND approved. News release from Adria Laboratories. March 12, 1992. Summary of preliminary analysis of study comparing ddI and ZDV [AZT]. Update from the National Institute of Allergy and Infectious Diseases. April 13, 1992. ********** DRUG INFORMATION AND CLINICAL TRIAL HOTLINE 1-800-874-2572 ENGLISH AND SPANISH Monday through Friday, 9 am - 7 pm EST FREE DIRECTORY OF OPEN AIDS/HIV TRIALS IN THE S.F. BAY AREA 415-476-9554 FREE ********** FDA ANTIVIRAL ADVISORY COMMITTEE RECOMMENDATIONS ON DDC AND DDI Ronald A. Baker, Ph.D. ddc/AZT Combination The FDA Antiviral Advisory Committee, a panel of medical experts, recommended on April 21 that FDA approve ddC/AZT combination therapy for HIV infection, not as n first-line treatment, but as an option for individuals who fail AZT monotherapy. The Committee urged further study of ddC / AZT combination treatment in individuals already treated with AZT, since almost all the data presented to them came from studies among patients with no prior anti-HIV therapy. The Committee also recommended against approval of ddC (Hivid) as monotherapy for HIV infection in people who fail or cannot tolerate AZT. Current FDA guidelines suggest ddI use in these patients. The Committee's recommendation against ddC monotherapy follows the recent halting of a study comparing ddC to AZT as a single agent treatment. This study (ACTG 11 4) indicates that ddC is less effective than AZT in preventing AIDS-related infections and prolonging survival among individuals who have never used AZT. In contrast, results of ACTG 119 showed no difference in benefit from AZT or ddC mono-therapy in people with up to 48 weeks of prior AZT treatment. The Committee reviewed 2 small studies presented in support of ddC / AZT combination therapy. Dr. Robert Schooley of the University of Colorado presented supporting data from an ongoing Burroughs-Wellcome trial designed to test for the emergence of viral resistance. The results showed that the ddC/AZT combination doubled the increase in T-helper cells compared to AZT used alone. The Committee then discussed whether T-helper count increase ultimately translates into clinical benefit. There was no clinical data presented on the combination, e.g., how did the regimen affect development of opportunistic infections and survival? Several Committee members polled by BETA expressed disappointment that the data presented did not show a clear clinical benefit from ddC/AZT combination treatment. "FDA approval of ddC will allow physicians to prescribe the drug to patients, regardless of their prior use of AZT or ddI. Once ddC is available by prescription, doctors can follow their own best judgment about which patients may benefit from the drug." FDA is likely to follow the Advisory Committee's recommendation, and will probably approve ddC use only in combination with AZT, as an option for people who experience disease progression on AZT monotherapy. If approved through the FDA's new accelerated approval program for drugs for life-threatening illnesses, ddC will also be subject to accelerated withdrawal from the market, if ongoing trials do not show that ddC/AZT combination treatment is better than AZT monotherapy. Still, FDA approval of ddC will allow physicians to prescribe the drug to patients, regardless of their prior use of AZT or ddI. Once ddC is available by prescription, doctors can follow their own best judgment about which patients may benefit from the drug. ddC/AZT combination treatment is currently available to individuals who qualify for one of the expanded access programs offered by the drug's manufacturer, Hoffmann-LaRoche. Participation in these programs is open to people with advanced HIV disease who fail or cannot tolerate AZT. Symptomatic HIV positive individuals with fewer than 300 T helper cells or asymptomatic individuals with fewer than 200 T-helper cells, who cannot participate in ongoing clinical trials, are also eligible to receive ddC for combination therapy. Hoffmann-LaRoche provides ddC free to these individuals, but the cost of laboratory work and physician monitoring must be borne by the patient. To find out more about inclusion and exclusion criteria for the ddC expanded access program, physicians may call Hoffmann-LaRoche at 800-322-2144 Monday through Friday, 9 am to 8 pm (Eastern Time). For information about the Hoffmann-LaRoche Cost Assistance Program for patients, call 800-227-7448 weekdays 8:30 am to 5 pm. Individuals who do not quality for ddC clinical trials or expanded access programs may still purchase bootlegged ddC from the Fort Lauderdale Buyers' Club (305-568-3001 ). When the FDA recently called for a halt to the sale of "impure" ddC at the San Francisco and New York buyers' clubs, the agency said the Florida group's "underground" supply of ddC was safe. ddI The FDA Antiviral Advisory Committee recommended on April 20 against expanding the availability of ddI (Videx), even after hearing promising results from a Phase III study presented by the drug's manufacturer, Bristol-Myers Squibb. This clinical trial (ACTG 116/117) shows that 500 mg/day ddI is more effective than 600 mg/day AZT in slowing HIV disease progression among individuals who have been taking AZT for at least 16 weeks. Researchers designed ACTG 116/117 to determine whether people who switched from AZT to ddI benefitted more than those who continued treatment with AZT. Individuals with asymptomatic or mildly symptomatic HIV infection using ddI experienced a slower rate of disease progression than those using AZT. In contrast, people with AIDS using ddI did not experience this benefit. The researchers found no difference in survival rates among participants taking either drug, an indication that the 2 drugs have a similar survival benefit when used alone. The investigators also reported on the observed side effects from each drug. Predictably, individuals on AZT developed lowered red and white blood cell counts more frequently than those on ddI. Pancreatitis developed in some people using 750 mg/day ddI. Interestingly, there was no difference in the groups regarding development of peripheral neuropathy. These data on ddI were promising enough for the Advisory Committee to feel it had acted wisely last year in recommending ddI approval for people who no longer benefit from AZT treatment or who cannot tolerate its side effects. The Committee recommended against changing the existing FDA guidelines on ddI, and the agency will likely follow its recommendations. Current Guidelines for Anti-HIV Therapy in Adults AZT Indication: Less than 500 T-helper cells or symptomatic Individual dosage: 100-200 mg Schedule: 3 times a day Toxicity: Anemia, Neutropenia, Nausea, Lethargy Monitoring: CBC Comments: First-line treatment. Only drug FDA-approved for initial treatment of HIV. ------------------------------------------------------------------- ddI Indication: AZT failure or intolerance. Fewer than 200 T- helper cells. Individual dosage: 125-300 mg. Schedule: Twice a day Toxicity: Neuropathy, Pancreatitis, Rash, Diarrhea. Monitoring: Amylase, Neurological exam. Comments: Second-line treatment. Now available through prescription. -------------------------------------------------------------------- ddC Indication: In combination with AZT for AZT monotherapy failure. Individual dosage: 0.375-0.75 mg Schedule: 3 times a day Toxicity: Neuropathy, Pancreatitis, Rash Monitoring: Amylase, Neurological exam. Comments: Not recommended as monotherapy. Available through expanded access programs. Physicians may call 1-800-ddC-21-HIV for details. ********** HYPERICIN FOR THE TREATMENT OF HIV DISEASE: AN UPDATE Bernard Bihari, M.D. Bernard Bihari is a physician in New York City with a private medical practice directed to the care of people with HIV infection. He has served as the principal investigator of several clinical trials of HIV/AIDS therapies. Hypericin, originally extracted from Hypericum Peforatum, the St. John's Wort plant, began its first clinical trial as a treatment for HIV infection in October, 1991 at New York University Medical Center. The raw dried plant has been used by traditional healers in many cultures for thousands of years to treat fevers and infected wounds. Studies in recent years have shown that a purified extract of the plant containing more than 90% hypericin demonstrates strong activity in the test tube against HIV without toxicity to the cells,[1,2,3,4,5] essentially stopping viral replication and release from infected cells. In addition, treatment with hypericin prevented illness and death in mice infected with the Freund leukemia virus, a mouse retrovirus uniformly causing death in mice from an AIDS-like illness in an average of 23 days. The mice recovered and survived for the entire followup period of 240 days.[1,6] The purified extract is similarly effective in protecting mice infected with the radiation leukemia virus, another mouse retrovirus causing a lethal AIDS-like illness.[6,7] Mice infected with either of these viruses show only a modest slowing of disease progression when treated with AZT and other nucleoside analogues.[6,7] A number of community-based clinical trials with the commercially available tinctures of St. John's Wort (such as Hyperforat and Psychotonin M) or tablets such as those produced by Yerba Prima have shown no apparent benefit in the treatment of HIV disease.[8,9] It has been noted, however, that the hypericin content of these tinctures and tablets, even when the products are taken in sizeable doses, is much too low to produce blood levels of hypericin equivalent to the concentrations necessary for efficacy in the in vitro and mouse models. "A purified extract of the plant containing more than 90% hypericin demonstrates strong activity in the test tube against HIV without toxicity to the cells, essentially stopping viral replication and release from infected cells." It is of interest that hypericin has also shown significant activity in vitro against several other viruses, including herpes simplex-1 (HSV-1 )[10,11] herpes simplex-2 (HSV-2),[11] influenza A,[10] murine and human cytomegalovirus[4,5] and the Epstein-Barr virus.[12] Anecdotal evidence in 12 patients to date suggests that the commercially available St. John's Wort extracts may have some efficacy in treating hepatitis B. One investigator has noted, in a small open label study, marked improvement in chronically elevated liver function tests due to hepatitis B in 7 patients with HIV infection and rapid clinical and laboratory recovery from acute hepatitis B in 3 patients who were significantly symptomatic treated with 12 Yerba Prima St. John's Wort tablets per day.[13] Hypericin has been synthesized by VIMRX Pharmaceutical, Inc. of Stamford, Connecticut, and became available for a Phase I trial at NYU in October 1991. U.S. patents for the synthetic compound and for a purified extract (containing more than 90% hypericin) were issued to NYU and the Yeda Research and Development Company Ltd. in September 1991, and drug development has been supported by VIMRX under a licensing agreement. Although public announcements in the Winter of 1989-1990 indicated that NYU would begin a Phase I trial of the purified extract by March 1990, with FDA approval, VIMRX decided to delay the trial until the synthetic compound was produced. Unfortunately, the synthetic compound did not become available for Phase I testing for 18 months after the originally planned starting date for the Phase I trial of the extract. In addition, Phase I testing of an oral product has been delayed because synthetic hypericin is not absorbed into the blood stream when taken by mouth. As a result, NIAID has contracted with the University of Iowa College of Pharmacy to develop a formulation of synthetic hypericin that is absorbed when taken orally. It is not known when an orally absorbable synthetic product will be available. According to a biochemist familiar with hypericin, it forms a crystalline-like structure that is neither water nor fat soluble when it is in a pure form. Hypericin is prevented from forming a crystalline structure when it is in combination with other substances in the plant. It's relationship with other substances in the plant therefore may be essential to its absorbability when taken by mouth. "If, in fact, hypericin prevents cell-to-cell transmission of HIV in patients as it appears to in vitro, long-term use could lead to a significant decline in the body's HIV load." The NYU Phase I trial began in late October 1991 with a starting dose of 0.25 mg per kg of body weight given intravenously twice a week (17.5 mg per dose in a patient weighing 70 kg or 154 lbs) with minimal side effects. When the dose was doubled to 0.5 mg per kg, several light-skinned patients developed severe sun sensitivity, requiring temporary discontinuance of the trial. With regard to the implications of this for oral formulations of hypericin, a number of people, probably several dozen, have been using 10 mg/day or more of hypericin extracted from the St. Johns Wort plant taken orally with very few adverse reports, including only 1 case of severe sunburn.[14] One clinician in New York is aware of a number of people taking highly concentrated extracts in doses of 40 mg of hypericin per day or more with no sun sensitivity.[15] The NYU Phase I trial was resumed in April 1992 at a dose of 0.25 mg per kg I.V. 3 times a week. The Phase I trial will also begin at some time in the near future at Beth Israel Hospital in Boston, in its ACTU clinic (617-735-4103) and at the University of Minnesota ACTU clinic in Minneapolis (612-625-1462). The phone number for information about volunteering for the trial at the New York University Medical Center ACTU clinic is 212-263-6565. Because of the delays in development of the drug, a clinical trial of a concentrated extract of the plant to be carried out in private physicians offices is in the planning stages. Hypericin may have considerable potential in the treatment of HIV disease. It appears in the oral form to have little toxicity. Its mechanisms of action make resistance on the part of HIV unlikely. If, in fact, it prevents cell-to-cell transmission of HIV in patients as it appears to in vitro, longterm use could lead to a significant decline in the body's HIV load. All cells in the body die and are eventually replaced (except neurons and ova). Most estimates involve complete replacement every 7 to 10 years. Some tissues such as the skin, lining of the gastrointestinal tract, bone marrow and lymph nodes have a much more rapid turnover. If hypericin completely prevented cell-to-cell transmission at blood levels that were not toxic, and did not trigger the development of resistance, the HIV load in the body could drop as much as 30% to 40% in the first year, with a gradual decline over time and the possibility that the body could eventually completely shed its HIV load. As the HIV load dropped, one would expect the CD4 count to gradually rise as the direct and indirect immune suppressive pressure of HIV declined (including decreases in the HIV-induced elevated levels of alpha interferon, tumor necrosis factor, interleukin-1, histamine, free floating gp160 and free floating gp41, as well as a decrease in direct HIV-induced cytotoxicity of CD4s). Thus the development of hypericin bears close watching by people with HIV disease, and the maintenance of pressure by the activist community to accelerate its development. References: 1. Lavie G et al. Studies on the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. Proceedings of the National Academy of Sciences 86:5963. 1989. 2. Valentine F. Hypericin: A hexahydroxyl dimethylnapthodiantrone with activity against HIV in vitro and against murine retroviruses in vivo (Abs.). Journal of AIDS 4(3):317. 1991. 3. Degar S et al. Inhibition of HIV infectivity by hypericin: Evidence for a block in capsid uncoating. Journal of AIDS 4(3):316. 1991. 4. Lopez-Bazzocchi I et al. Antiviral activity of the photoactive plant pigment hypericin. Photochemistry Photobiology 54:95-98.1991. 5. Barnard D et al. Evaluation of the antiviral activity of anthraquinones, anthrones and anthraquinone derivatives against human cytomegalovirus. Antiviral Research 17:63-77. 1992. 6. Meruelo D et al. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: Aromatic polycyclic anthrones hypericin and pseudohypericin. Proceedings of the National Academy of Sciences 85:5230. 1988. 7. Ruprecht B et al. Suppression of mouse viraemia and retroviral disease by AZT. Nature 323:467-469. 1986. 8. Bihari B. Personal Communication. 9. Payne D. Personal Communication. 10. Tang J et al. Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses. Antiviral Research 13:313-25. 1990. 11. Anderson D et al. In vitro virucidal activity of selected anthroquinones and anthraquinone derivatives. Antiviral Research 16:185-196. 1991. 12. Meruelo D. Personal Communication 13. Bihari B. Personal Communication. 14. AIDS Treatment News, issue 146. March 6, 1992. 15. Bihari B. Personal Communication. ********** TAT, PROTEASE AND THE HOFFMANN-LAROCHE HIV COMMUNITY ADVISORY BOARD A Conversation with BETA Editor Ronald Baker Edwin B. Brown The pharmaceutical firm Hoffmann-LaRoche, manufacturer of the anti-HIV drug ddC, recently named 10 HIV community representatives from across the U.S. to serve on its first HIV Community Advisory Board. In the interview below, BETA editor and Board member Ronald Baker reports on discussions of ddC/AZT combination therapy and the Tat and protease drugs at the first meeting between HIV community representatives and Roche scientists and managers in New York on April 6. Edwin B. Brown is a medical writer and free-lance journalist living in San Francisco. BETA: What drug treatments were discussed at the Board meeting? BAKER: As you would expect, ddC / AZT combination treatment and the Tat and protease drugs dominated the agenda. First, Dr. Waijeh Soo reviewed the available data on ddC / AZT combination treatment. This was followed by discussion of a so-called Large Simple Trial (with 20,000 study participants) to further evaluate the effectiveness of ddC/AZT combination treatment. After that, Dr. Richard Ginsberg discussed past, present and proposed studies for the Tat drug, followed by a presentation on the protease inhibitor by Dr. John Sullivan-Bolyai. BETA: What is the Tat gene inhibitor? BAKER: Simply stated, Tat is a gene of HIV, a protein substance whose production is necessary for HIV to replicate. The Tat gene inhibitor created by Roche scientists is an extremely potent method for stopping HIV replication, at least in the test tube. We don't know yet if it will work in humans. "The Tat gene inhibitor created by Roche scientists is an extremely potent method for stopping HIV replication, at least in the test tube. We don't know yet if it will work in humans." The Tat drug may be important for several reasons. For one, it interferes with HIV replication differently than AZT, ddI or ddC, and this alone makes it an attractive candidate for use in combination with these drugs. Like AZT, ddI and ddC, the Tat drug suppresses the spread of HIV into uninfected cells, but unlike these 3 treatments, it can also inhibit HIV replication in cells already infected with the virus. If the Tat drug produces these effects in humans without causing significant toxicities, it will be regarded as a major breakthrough in the treatment of HIV infection. The Tat drug also appears to be synergistic with AZT and ddC. In laboratory tests, it's effective against both HIV-1 and HIV-2, and has shown no major toxicities. The most commonly reported side effects have been headache and drowsiness. BETA: No other side effects? BAKER: One other. In animal studies, the drug produced a yellow pigmentation of the skin that reversed when the drug was stopped. In early human studies, used at a moderate dose, the drug caused a yellowing of the urine. It's possible that use of higher doses may produce a noticeable yellowing of the skin. Fortunately, the pigmentation doesn't seem to occur as the result of toxicity to a human organ. BETA: And the protease inhibitor, why is it considered a promising antiHIV drug? "Like AZT, ddI and ddC, the Tat drug suppresses the spread of HIV into uninfected cells, but unlike these 3 treatments, it can also inhibit HIV replication in cells already infected with the virus." BAKER: Successful replication of HIV depends in part on its ability to produce an enzyme called protease. The Roche protease inhibitor prevents production of this enzyme, at least in test tube studies. It also works synergistically with AZT, ddI and ddC, and it's active against HIV-resistant strains of AZT. BETA: What about toxicity? BAKER: According to Dr. Sullivan-Bolyai at Roche, minimal toxicities, even at high concentrations of the drug. BETA: These 2 drugs sound too good to be true. Do they have a downside? BAKER: Well, we don't know yet if they work in humans like they do in the laboratory, so that's a big unknown. We need more data from human studies. BETA: How long before we know if these drugs work in HIV positive individuals? BAKER: We'll know soon--in a matter of a few months--whether these drugs show strong anti-HIV activity in humans. The chief clinical investigator for the Tat gene work group, Dr. Richard Ginsberg, told us about plans for a 4-month Phase I/II study of 100 patients with advanced disease starting sometime this summer. Researchers will be looking for activity against HIV as well as for more pharmacokinetic information. "The Tat drug also appears to be synergistic with AZT and ddC. In laboratory tests, it's effective against both HIV-1 and HIV-2, and has shown no major toxicities." BETA: And the protease inhibitor, is it in human testing yet? BAKER: Yes, in England, France, Italy and the U.S. The Italians are conducting a dose-ranging study of the protease drug plus AZT in previously untreated people with advanced HIV disease. We were told that a U.S. study could begin by Fall, a dose-ranging study in viremic individuals. So, we could have important information on the activity of this drug in humans by the end of this year. BETA: Any other important information about the protease inhibitor? BAKER: Again, we don't know if it will fulfill the early promise shown in laboratory studies. Also, the current oral formulation of the drug has a low bioavailability. People in studies will be taking up to 9 capsules 3 times a day. "The Tat and protease drugs are arguably the most important new anti-HIV treatments under study. They must be tested as rapidly as possible." BETA: How would you summarize the significance of these 2 drugs? BAKER: The Tat and protease drugs are arguably the most important new anti-HIV treatments under study. They must be tested as rapidly as possible. If they fulfill their early promise, these drugs may bring significant clinical benefits to people with HIV infection, improve their quality of life and prolong their survival. ******** GLOSSARY ACTG: the AIDS Clinical Trial Group. U.S. medical centers evaluating treatments for HIV and HIV-associated infections; ACTG studies are sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). ALPHA INTERFERON: one of 3 major classes of interferon that the body produces in response to viral infections. In people who are HIV-positive, elevated levels of "acid labile" alpha interferon may indicate disease progression. Genetically engineered alpha interferon is an FDA-approved treatment for KS. The drug is being studied at low doses and in combination with AZT as an anti-HIV therapy. AMELIORATE: to make better or more tolerable. AMYLASE: a class of enzymes (proteins); an abnormal increase in amylase levels may indicate pancreatitis. ANALGESIC: an agent that relieves pain. ANATOMIC: relating to anatomy, the science of the structure of the animal body and the relationship of its different parts. ANEMIA: a condition marked by an abnormally low number of red blood cells. ANERGY: lack of a response to the injection of a certain foreign substance. This may indicate the inability of the immune system to mount a normal allergic response. ANGIOGENESIS: the growth and proliferation of blood vessels. Angiogenesis inhibitor are compounds that block this process, and 2 of them are under study as treatment for Kaposi's sarcoma (KS). ANGIOSTATIC: stopping or inhibiting the growth of new blood vessels (see also angiogenesis above). ANTI-ARRHYTHMIC: relating to drugs that help to normalize the rhythm of the heartbeat. ANTIBODY: a protein substance, developed in response to an antigen, that destroys or neutralizes bacteria, viruses or other harmful toxins. This antigen/antibody reaction forms the basis of immunity. In HIV disease, San Francisco AIDS Foundation Hotline 415-863-2437 English / Spanish / Filipino antibodies to HIV are only partially protective. ANTIDEPRESSANT: a drug that prevents or relieves depression by lifting the mood and decreasing or eliminating other depressive symptoms. ANTIGEN: a substance that stimulates an immune response. The immune system recognizes these substances as being foreign, and produces antibodies to "fight" them. This antigen/antibody response is an important part of immunity. ANTIRETROVIRALS: agents used to suppress the activity of retroviruses, such as HIV. AZT: azidothymidine; also called zidovudine (trade name Retrovir). A thymidine analog that suppresses replication of HIV. It is the only drug FDA-approved for the initial treatment of HIV infection. Adverse side effects may include anemia, leukopenia, muscle fatigue, muscle wasting, nausea and headaches. BETA-2 MICROGLOBULIN: a protein found in the blood. Higher than normal amounts of this protein in the blood indicate replication of HIV and progression of HIV disease. BIOAVAILABILITY: the rate and extent to which a substance is absorbed and circulated in the body. BIOTIN: one of the B vitamins essential for normal metabolism; found in egg yokes, liver, tomatoes and Yeast. CANDIDA: refers to candida albicans, a yeast-like fungus that can infect the skin, nails, blood or mucous membranes throughout the body, including the throat, vagina, intestines and lungs. Oral and vaginal candidiasis are often an early sign of an impaired immune system in HIV positive individuals. COMPLETE BLOOD COUNT (CBC): a screening of the most important components in the blood. These include the total white blood count, the breakdown and counting of white blood cells, the red blood count, hemoglobin levels and platelets. cc: abbreviation for cubic centimeter. CODEINE: a pain-relieving narcotic drug made from opium or morphine. CRYPTOCOCCAL MENINGITIS (CM): a fungal infection of the membrane layers of the brain and spinal cord. Symptoms may include headache, confusion, blurred vision, fever and speech difficulties. Left untreated, CM can lead to coma and death. Oral fluconazole (Diflucan) and amphotericin B are equally effective in treating individuals at low risk for treatment failure. CULTURE: the growth of microorganisms or living tissue in the laboratory, in solutions that promote their growth. CYTOTOXICITY: the quality of being capable of producing a specific toxic action against cells. DNA: deoxyribonucleic acid; material in the nucleus of a cell that contains the cell's genetic code. ENZYME: a protein that can produce chemical changes in other substances without being changed itself. ETIOLOGY: the study of the causes of diseases. FDA: the Food and Drug Administration; the agency of the federal government responsible for the regulation of drug development. FECAL: relating to feces (excrement). GENE: the biologic unit of heredity; genes are self-reproducing and are located at a definite position on a particular chromosome; genes determine many aspects of human physiology. HUMAN PAPILLOMAVIRUS (HPV): the human papillomavirus is a viral infection that causes warts or nipple like protrusions. HPV has also been associated with cervical cancer in women and anal cancer in men. HYDROCORTISONE: also called cortisol, a substance excreted by humans in only small amounts. The synthetic form of cortisone in a cream form is used to reduce skin inflammations. IMMUNOGLOBULIN: proteins that can act as antibodies to help the body fight off disease. Recombinant and pooled immunoglobulins from blood donations have been used successfully to help HIV-infected children and some adults resist bacterial infections. INTERLEUKIN: chemical hormone messengers secreted by and having effects on many different cells in the immune system. INTRAVENOUS (I.V.): within or into the veins. Intravenous drugs are injected directly into the veins. LIPOSOME: a spherical particle of fat or oil suspended inside a cell or in the bloodstream. LYMPH GLANDS/LYMPH NODES: small,bean-shaped organs made up mostly of lymphocytes (white blood cells) and connective tissue. Lymph glands are widely distributed in the body and are essential to the functioning of the immune system. MAC (MYCOBACTERIUM AVIUM COMPLEX): a disease caused by 2 bacteria found in water, soil and food. In PWA, it can spread through the bloodstream to infect lymph nodes, bone marrow, liver, spleen, spinal fluid, lungs and intestinal tract. Symptoms of MAC include prolonged wasting, fever, fatigue and enlarged spleen. MALIGNANCY: a neoplasm or tumor replicating out of control and invading tissue and causing damage to that tissue. MUMPS: a contagious disease that occurs mainly in children. MYCOBACTERIUM: a group of organisms similar to bacteria that may cause disease, especially in people with poor immunity. NEUROLOGIC (NEUROLOGICAL): concerning the central nervous system (brain and spinal cord) or the peripheral nervous system (the rest of the nervous system) and/or diseases of these systems. NEUROPATHY: any disease of the central nervous system (brain and spinal cord) or the peripheral nervous system (the rest of the nervous system). NIAID: National Institute of Allergy and Infectious Diseases. One of the institutes of the National Institutes of Health (NIH) which is part of the Public Health Service of the federal government. The NIAID is responsible for the federally-funded national AIDS research program. NOSOCOMIAL: denoting a new disorder (not the original condition) associated with being treated in a hospital, such as a hospital-acquired infection. PANCREATITIS: inflammation of the pancreas, a gland that helps in food digestion; symptoms may include intense abdominal pain, nausea, vomiting, constipation and possibly jaundice; pancreatitis can be life-threatening. PHARMACOKINETIC: concerning the study of how a drug is processed by the body, with emphasis on the time required for absorption, duration of action, distribution in the body and method of excretion. PHASE I STUDY: the first step in human testing of a drug. It is designed to evaluate drug toxicity at different dose levels, and usually involves a small number of participants. PHASE II TRIAL: the second step in the evaluation of a drug in humans, a Phase II trial is designed to evaluate drug effectiveness. Phase II trials proceed only if one or more Phase I trials have shown the drug's toxicity to be acceptable within a given dose range. PHASE III TRIAL: expansion of Phase II trial to 300 to 3,000 volunteers; designed to back-up information gathered in Phase I and II; also compares the drug to other agents, either alone or in combination. PLACEBO: an inert, inactive substance. In placebo-controlled drug studies, a placebo is given to one group of patients, while the drug being tested is given to another group. The results obtained in the 2 groups are then compared, allowing for optimal evaluation of the drug under study. PLACEBO-CONTROLLED STUDY: a method of investigation of drugs in which an inactive substance (the placebo) is given to one group of patients, while the drug being tested is given to another group. The results obtained in the two groups are then compared. PLASMA: a fluid that carries blood cells and nutritive substances throughout the body. Plasma also carries metabolic waste products from body organs and is a medium for chemical communications between different parts of the body. PLATELET: a type of blood cell that facilitates blood clotting. PLENARY: a meeting, usually a large conference that is open to all conference participants. POLYMERASE CHAIN REACTION (PCR): a highly sensitive test that can detect minute amounts of DNA fragments of viruses or other organisms in blood or tissue. PPD: abbreviation for purified protein derivative of tuberculin (an extract made from cultures of M. tuberculosis). PPD refers to a skin test used to detect tuberculosis. PROPHYLAXIS: treatment that helps to prevent a disease or condition before it occurs or recurs. PROTAMINE SULFATE: a protein substance given intravenously as an antidote to overdosage with the drug heparin, an agent used for its anticoagulant properties. REPLICATE: to duplicate or reproduce. RESISTANCE (TO A DRUG): the ability of an organism, a micro-organism or a virus to lose its sensitivity to a drug. For example, after longterm use of AZT, HIV can develop strains of virus in the body that are no longer suppressed by this particular drug, and therefore are said to be resistant to AZT. RIMMING: a sexual activity involving one partner's tongue and mouth in contact with the other partner's anus and possibly their fecal excrement. SPUTUM: mucus or other matter ejected from the throat by coughing or spitting. STD: sexually-transmitted disease. SYNERGISTIC: the action of 2 or more drugs that, when taken together, have an effect greater than the total effect of the individual drugs. TAT GENE INHIBITOR: the tat gene is the gene in HIV that regulates the rate of replication of the virus; when turned off or inhibited, HIV remains inactive and will not produce new virus nor infect other cells. The tat gene inhibitor is a drug (RO 247429) produced as an anti-HIV agent by Hoffman-LaRoche; the drug is currently in Phase I/II testing at various sites. TELEOLOGIC: relating to a natural process directed toward an end or shaped by a purpose. TETANUS TOXOID: inactivated form of tetanus protein used to elicit an immune response observable on the skin. T-HELPER CELLS: a type of white blood cell (also known as CD4 and T-4 cells) which help the body fight off infections. HIV invades these cells and weakens or destroys them. Physicians need to regularly monitor T-helper cell counts in HIV-infected individuals in order to help give them an idea of the progression of H~V infection. The "normal" range for T-helper cells is 480-1800, but this may vary, depending on where the test is given. HIV-infected individuals with T-helper cell counts below 500 may want to seriously consider antiviral therapy. TITER: standard of strength, per volume of a test solution. TYLENOL: a brand name for acet- VIREMIC: relating to the presence aminophen, a drug used to reduce of virus in the blood or plasma. pain and fever. ZIDOVUDINE: see AZT. UCSF: the University of California at San Francisco Medical Center. ********** BETA Editor Ronald A. Baker, Ph.D. Contributors to This Issue Bernard Bihari, M.D. Edwin B. Brown Marcus Conant, M.D. Holly Ladd Jonathan Mann John Willoughby Ronald A. Baker, Ph.D. Scientific Advisors Harvey S. Bartnof, M.D. Henry M. Chance Toby Dyner, M.D. Mitchell Katz, M.D. Merritt Smith, M.D. Editorial Production Stewart Baron Production David Hecht Design Larry Stinson BETA is published quarterly by the San Francisco AIDS Foundation. Funding provided by private and corporate donations. Copyright (c) 1992 by the San Francisco AIDS Foundation. All rights reserved. For subscription information call 415-863-2437. Editorial office: P.O. Box 426182, San Francisco, CA 94142.