Opening Session 1
Long-Acting PrEP Agents in HIV Prevention
David D. Ho, Scientific Director and CEO, Aaron Diamond AIDS Research Center; Irene Diamond Professor, The Rockefeller University, New York, NY, USA
There is no effective vaccine to protect against HIV infection today, and none will be available for the foreseeable future. The lack of an effective HIV vaccine is in part due to the structural properties of the viral envelope glycoprotein, which possesses highly variable amino-acid sequences along with extensive glycosylation that shield the virus from many anti-envelope antibodies. As an alternative strategy, our group is pursuing the use of antibodies as agents for passive administration to prevent HIV infection. We have engineered a number of bi-specific monoclonal antibodies that have remarkable potency and breadth against the virus in vitro. We have in hand a number of constructs with 100% breadth against a large panel of HIV strains with potency in the nM range. Several of these constructs are now being evaluated as candidates for clinical development. In addition, our group has pursued a slow-release formulation of the integrase inhibitor cabotegravir (formerly known as GSK744LA) against HIV. The pharmacokinetic profile of cabotegravir in humans suggests that it could be administered as an injectable once every 3 months. In protection experiments against virus challenges in monkeys, this drug has shown high degrees of protection. We firmly believe that this long-acting integrase inhibitor is a promising agent for HIV prevention in high-risk populations. We are finishing a Phase-2 study at this time, and multiple Phase-3 efficacy studies are being planned.
A Brief Biography of David D. Ho
David D. Ho, M.D. is the founding Scientific Director and Chief Executive Officer of the Aaron Diamond AIDS Research Center, a world-renowned biomedical research institute. He is also the Irene Diamond Professor at The Rockefeller University.
Dr. Ho received his degrees from California Institute of Technology (1974) and Harvard Medical School (1978). Subsequently, he did his clinical training in internal medicine and infectious diseases at Cedars-Sinai Medical Center/UCLA School of Medicine (1978-1982) and Massachusetts General Hospital/Harvard Medical School (1982-1985), respectively.
Dr. David Ho has been at the forefront of AIDS research for 34 years, publishing over 400 papers. His elegant studies, beginning in 1994, unveiled the dynamic nature of HIV replication in vivo and revolutionized our basic understanding of this horrific disease (Nature 1995; Science 1996). This knowledge led Dr. Ho to champion combination antiretroviral therapy (N. Engl. J. Med. 1995; Science 1996) that resulted in unprecedented control of HIV in patients (Nature 1997). AIDS mortality in richer nations has declined dramatically since 1996, and a massive international effort is now underway to bring such life-saving treatment to millions in the developing world. To date over 10 million patients have benefitted from combination antiretroviral therapy. Dr. Ho has been the major driving force behind this major medical breakthrough in what is arguably the worst plague in human history.
Dr. Ho's research team is now devoting considerable efforts to develop HIV vaccines, as well as antibody-based strategies and long-acting antiretroviral drugs as pre-exposure prophylaxis to halt or slow the spread of the AIDS epidemic.
Dr. Ho has received numerous honors and awards for his scientific accomplishments. He is the recipient of thirteen honorary doctorates (including from Swarthmore, Tufts, Columbia, Tulane, University of Natal, and Tsinghua University). He has been chosen as the commencement speaker at Caltech, MIT, and Harvard School of Public Health. Additional accolades include the Ernst Jung Prize in Medicine, Mayor's Award for Excellence in Science & Technology, the Squibb Award, and the Hoechst Marion Roussel Award. Dr. Ho has been elected as a member of the American Academy of Arts and Sciences, Academia Sinica (Republic of China), Chinese Academy of Engineering, and the Institute of Medicine, National Academy of Science in the United States. He was also inducted into the California Hall of Fame. Recently, Dr. Ho was recognized by the Kingdom of Thailand with the Prince Mahidol Award in Medicine.
Dr. Ho was a member of the Board of Overseers of Harvard University and a board member of the MIT Corporation. He is currently a member of the board of trustees of the California Institute of Technology.
Dr. Ho was named Time Magazine's Man of the Year in 1996, and was the recipient of a Presidential Medal from Bill Clinton in 2001.
Opening Session 2
An Editor's Insights into Writing a Scientific Paper
It is important to remember why we write scientific papers. It is not (just) to improve our CV and scientific profile. Particularly in medical research, there is an ethical imperative to publish the results of research we have undertaken so that other people are not subjected to unnecessary risk. The scientific paper is therefore about communication. An author's task in to ensure that the message is clear to the readers. Presentation is important. A visually attractive and well-organised manuscript helps the reader. Use an easily read font (for example, Calibri or Arial; 11-12 point) with double spacing.
The first reader will be the editor of the journal. As a gate-keeper to publication, it is essential that the author communicates the message clearly to the editor. The covering letter (1 page) should explain in simple, non-technical language the novelty, the importance of the question, the importance of the conclusion, and the reason why the paper is appropriate for the journal.
Because you need to communicate your message, writing style is important. A paper that is poorly structured and difficult to understand will not engage the readers' attention. Crucial aspects are the use of simple language, avoiding abbreviations and using short sentences. One point in each sentence (no more than 30 words).
Pay attention to the Title and the Abstract. A long title suggests thinking is not clear and warns the reader the manuscript might be difficult to follow. The Abstract is very important. Most people only read the Abstract, so the important messages you wish to convey to the reader must be included here. Most journals have a strict specified word-count for Abstracts; do not exceed this.
The standard structure of a scientific paper helps with writing and reading, but things must be in the correct place. The Introduction should be short. It should usually not exceed 3 paragraphs and should end with the aim of the research, or the hypothesis being tested. Methods should be described (or referenced) sufficiently that the work could be repeated by others. Results should be clearly and logically described. Do not repeat data from tables and figures in the text. Discussion should put the results in context. Start with a one-sentence summary of the main result. It is much more important to discuss the limitations of your work the strengths. Discuss the implications - both clinical and for the next phase of research. End with a strong statement.
Figures should be clear and simple. Do not put too much in any one figure. Figures tell the story; tables provide essential detail. Long or complex tables probably provide fine details and might be better placed as an online appendix. Do not over-reference the paper. Chose references carefully and make sure they are the most appropriate.
Follow the guidelines. Guidelines such as CONSORT for randomised trials are there to help you remember what is needed for proper evaluation of your work. Pay special attention to the responsibilities of authorship. Only the few who meet the International Committee of Medical Journal Editors' guidelines can be authors. Editors expect you to follow the specific guidelines they have produced for their journal.
Dr Stuart Spencer
Stuart joined The Lancet in 1999 and throughout his time there has led the Fast Track team that aims to select, review and publish prestigious manuscripts within 4 weeks of receipt. Although Fast Track reviews all areas of research, Stuart deals with the cardiology submissions.
After graduating Stuart moved into research doing a PhD at the Brompton Hospital, London, looking at scoliosis in children before moving to the Veterinary School campus at Bristol University. During this period he was invited to establish a research unit in The Netherlands. Later he set up a research team for a major pharmaceutical company in Switzerland, and then spent 9 years as a senior researcher in New Zealand. He has also had two senior research fellowships at Leuven University, Belgium, visiting professorships at King's College, London and Hong Kong University, and a doctorate of medicine from Umea University, Sweden. Stuart's research expertise includes such diverse topics as, growth, neuroendocrinology, immunology and fetal development. He also had a Senior Fellowship in bioethics. This broad research base in front-line research has given a clear understanding of principles in research and publications applicable across disciplines.
Stuart is also a Trustee of the Scoliosis Association (UK), is on the British Scoliosis Research Fund grants committee and the steering Committee of the Swedish national GP Research School.
Plenary Lecture 1
Innovations in Nucleoside/Nucleotide Research Leading to Advances in Antiviral Therapy
John C. Martin
Gilead Sciences, Foster City, CA
Active site directed viral polymerase inhibitors have been the mainstay of antiviral therapy for decades. For instance, the first major drugs for HIV/AIDS patients were the nucleoside analogues AZT, ddI, 3TC, and D4T. In human target cells, these nucleoside analogues are first phosphorylated to a 5'-monophosphate and then ultimately to the corresponding triphosphate. The triphosphate serves as a substrate for the viral polymerase and terminates replication of the genome. These early generation nucleoside analogues demonstrated some significant safety and tolerability issues, but nevertheless as drugs prolonged the lives of countless HIV infected individuals around the world including those in low/middle income countries.
Over the last 15 years, a new class of drugs called nucleotides has come to predominate. Nucleotide drugs are stable versions of nucleoside 5'-monophospates and can more effectively target virus infected cells because of superior pharmacology. During this time, tenofovir DF (TDF) has become the predominate backbone agent for chronic therapy of HIV and hepatitis B infection. A measure of the success of TDF is that 80% (1 million) of HIV treated patients in upper income countries are on this medication. An additional 8 million individuals benefit from TDF in low/middle income countries. This success is due to the safety and efficacy of TDF and because it has been combined with other agents to provide 3 different daily single tablet regimens. This profile has allowed for an ongoing evolution of treatment guidelines to recommend all patients initiate therapy at the time of diagnosis. Thus, TDF has provided the foundation for treatment as prevention and in the form of Truvada to initiate preexposure prophylaxis in HIV negative high risk individuals, two strategies to lower a community burden of disease. Finally, a new tenofovir prodrug TAF that improves on the safety profile of TDF will begin to become available to HIV patients starting in late 2015.
Over the last three years, the nucleotide analogue sofosbuvir has revolutionized treatment of hepatitis C infection. Historical treatment of this disease with one year of peg-interferon, ribavirin plus/minus a protease inhibitor was so poorly tolerated that only a small subset of patients could be treated with a moderate cure rate. Now a single tablet regimen containing sofosbuvir can cure the large majority of patients treated for only 12 weeks. As of the end of summer 2015, over half a million individuals have initiated treatment with a sofosbuvir containing regimen.
This presentation will provide an overview of the scientific accomplishments leading to these therapeutic advances with nucleotide analogues.
John C. Martin, PhD
Chairman and Chief Executive Officer, Gilead Sciences, Inc.
Dr. Martin joined Gilead Sciences in 1990 and currently serves as Chairman of the Board of Directors and Chief Executive Officer. He served as President and Chief Executive Officer from 1996 through May 2008. Prior to joining Gilead, Dr. Martin held several leadership positions at Bristol-Myers Squibb and Syntex Corporation.
Dr. Martin serves on the University of Southern California Board of Trustees.
Dr. Martin previously served as President of the International Society for Antiviral Research, Chairman of the Board of Directors of BayBio and Chairman of the Board of Directors of the California Healthcare Institute (CHI). He served on the National Institute of Allergy & Infectious Diseases Council, the Board of Directors of the Biotechnology Industry Organization, the Board of Directors for CHI, the Board of Trustees of the University of Chicago, the Board of Trustees of Golden Gate University and the External Scientific Advisory Board of the University of California School of Global Health. Additionally, Dr. Martin served on the Centers for Disease Control/Health Resources and Services Administration's Advisory Committee on HIV and STD Prevention and Treatment and was a member of the Presidential Advisory Council on HIV/AIDS.
Dr. Martin holds a PhD in organic chemistry from the University of Chicago and an MBA in marketing from Golden Gate University. He has received the Isbell Award from the American Chemical Society and the Gertrude B. Elion Award for Scientific Excellence from the International Society for Antiviral Research. In 2008, Dr. Martin was inducted into the National Academy of Engineering of the National Academies.
Plenary Lecture 2
Prevention of HIV Infection in 2016 and Beyond
Myron S. Cohen, University of North Carolina at Chapel Hill
HIV prevention research has contributed to a falling incidence of HIV in many countries, and in some key populations. HIV prevention strategies can be broadly divided into vaccine and non-vaccine related. Vaccine strategies have reached a milestone with focus on improving on one successful trial (RV144), and increasing knowledge of broad neutralizing antibodies (bnABs). The most advanced bnAB trial is HVTN 703/HPTN 081, a Phase 2b study designed to determine if VRC01 given every 8 weeks (for passive immunity) reduces acquisition of HIV in men who have sex with men (MSM) and transgender participants in the Americas (n=2400) and women in sub Saharan Africa (n=1500). Non-vaccine HIV prevention has recently focused on optimal use of antiviral treatment. Successful ART (that limits HIV replication) greatly reduces sexual transmission of HIV. The HPTN 052 trial was completed in May, 2015. HIV serodiscordant couples were followed for 8494 person years. By intention to treat analysis ART (combined with counseling and condoms) reduced a virologically linked HIV transmission event (from infected person to partner) by 93%. Linked transmission events (n=8 total) were only observed early in treatment before antiretroviral agents could prove effective, or when treatment failed. Unlinked transmission event occurred in 1/300 person years of follow up. "Treatment as prevention" is a credible strategy if enough people, and the people most likely involved in ongoing transmission can be successfully treated. However, this strategy has yet to be proven at the population level and community based randomized controlled trials exploring this idea are underway. Alternatively, ART can be used as pre-exposure prophylaxis (PrEP). Tenofovir- emtricitabine can prevent HIV acquisition, but the magnitude of benefit depends on adherence, and men may benefit more than women. Potent newer drugs (rilpivirine, cabotegravir) delivered as nanosuspensions provided every 8-12 weeks are being explored for PrEP. HPTN 083 is a Phase 2b trial designed to determine whether cabotegravir can prevent HIV acquisition in MSM in the Americas (n=4500 subjects). ART can also be provided as a topical agent. In early 2016, the results of two large trials examining the ability of dapivirine impregnated rings used intravaginally (monthly) to prevent HIV will be reported. The most immediate and available HIV prevention lies in inspiring reduced risk taking procedure. Strategies that reduce risk are in constant development, and the use of behavioral economic tools such as cash transfer(s) have had mixed results, but great potential. In the absence of a highly effective vaccine, HIV prevention will continue to depend on implementation of a combination of tools that have proven effective.
Myron S. Cohen, MD
Associate Vice Chancellor for Global Health
Director, UNC Institute for Global Health and Infectious Diseases
Chief, Division of Infectious Diseases
Yeargan-Bate Eminent Professor of Medicine, Microbiology and Immunology, and Epidemiology
University of North Carolina School of Medicine
Institute for Global Health and Infectious Diseases
Myron S. Cohen is the Yeargan-Bate Eminent Professor of Medicine, Microbiology and Epidemiology at University of North Carolina at Chapel Hill. He completed his medicine training at the University of Michigan and infectious disease training at Yale University. Dr. Cohen is the Director of the UNC Institute for Global Health and Infectious Disease, and the co-principal investigator of the NIH HIV Prevention Trials Network (HPTN). He is a member of the Institute of Medicine, the American Society of Clinical Investigation and the American Association of Physicians. Dr. Cohen's awards include the Distinguished Career Award for lifetime achievement in STD/HIV research from the American Sexually Transmitted Diseases, the Smadel Award from the Infectious Disease Society, the O. Max Gardner Award from UNC, and the Award for Science from the State of North Carolina, the highest honor in the state. Dr. Cohen lead the HPTN 052 trial which demonstrated that antiretroviral treatment of people with HIV infection prevents the sexual transmission, recognized by Science Magazine as the "Breakthrough of the Year" in 2011. Dr. Cohen is the author of more than 500 publications and two books. Dr. Cohen's three decades of research has focused on prevention of the sexual transmission of HIV with extensive work in Malawi and the People's Republic of China.
Role of World Health Organization Towards Ending AIDS Endemics
Professor for Global Initiatives, Keio University
Former Assistant Director-General, WHO
The first 15 years of the 21th century have seen great progress in the fight against three major infections; HIV/AIDS, tuberculosis and malaria, under the framework of the MDGs. In many low income countries, the massive inflow of external fundings achieved decline of both mortality and morbidity, breaking the vicious cycle of poverty and ill health. However, many affected persons are still waiting for health services. Furthermore, HIV communities have reasons to worry about the consequence of the end of the MDGs by the end of 2015 and the emerging new paradigm of SDGs, in fear of diluting the legendary efforts so far.
In recent years, global health discussions have shifted from communicable to non-communicable diseases and health systems, until the Ebola crisis in West Africa gave a hard lesson for every party including WHO.
In this keynote lecture, the following points will be discussed;
- Progress of HIV/AIDS control and its architecture
The remarkable progress will be reviewed and partnerships such as UNAIDS, GF, UNITAID and BMGF will be mentioned.
- SDGs and emerging global health architecture
Triggered by both SDGs and Ebola response, discussion on the global health architecture is activated.
- Lessons learned and way forward: implication for the work of WHO
Ongoing work of WHO will be reviewed and placed within a wider context of global health.
WHO has been a strong team player in the complicated and competitive environment of global health, and HIV/AIDS can offer a good case study in terms of its contribution, potentials and limitations. (1569 characters including spaces)
The views expressed in this summary are those of the author and do not necessarily reflect the official position of WHO.
Dr. Hiroki Nakatani is presently Professor for Global Initiatives at Keio University. He served as Assistant Director-General of WHO from March 2007 to May 2015. He led the largest technical cluster comprising HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases, with a staff of more than 300 multi-nationals. During his tenure, the morbidity and mortality of these three major infections showed trends of decline, and a few tropical diseases were on track towards elimination and even eradication in case of dracunculiasis (guinea worm disease). Before joining WHO, he worked at the Ministry of Health, Labour and Welfare of Japan. During a long career at the Ministry, he acquired extensive technical experience in public health including tuberculosis and HIV/AIDS, as well as immunization, non-communicable diseases, health promotion, health emergencies, management of national hospitals and health workforce development. Dr Nakatani received his M.D. from Keio University School of Medicine, M.H.P.Ed from the University of New South Wales, and Ph.D. from Keio University.