Tuesday, March 25, 2008

I organized and ran what might be an historic meeting today on the future of HIV Vaccine Research. Ever since the disappointing results from the STEP trial (Merck ad5 prime-boost – see above), there has been increasing pressure within ourselves and in the scientific and certain activist communities to re-evaluate whether we should turn the knob of support more towards basic discovery as opposed to clinical trials of vaccine candidates for an HIV vaccine. On Nov. 16, 2007 I received a letter from a group of basic scientist/animal model HIV researchers asking to meet with me following the failed STEP trial in which vaccinated people with pre-existing Ad5 titers actually seemed to have an increased risk of HIV acquisition compared to placebo. They felt that we were wasting money on vaccine trials which they claimed had no basis to predict success based on animal model data. They were particularly concerned about going ahead with Gary Nobel’s VRC trial –PAVE 100 that tested 3 DNA primes followed by an Ad5 boost. However, others point out that the animal model has not been validated in the human and so unfortunately, we are really flying blind. In any event, in a manner similar to how I handled the AIDS activists >20 years ago in that same room (31/7A-24), I listened and suggested that we have HIV Vaccine Summit to discuss the direction of AIDS research. Hence the meeting today. Just a few days ago, a group called AIDS healthcare Foundation stated that we should stop ALL HIV vaccine research and put the money towards proven prevention activities. We had the Summit today and it was enormously successful. I played an active leadership role in the process as opposed to just listening. The meeting was chaired by Warner Greene and Adel Mahmoud and there were 3 panels: 1) basic discovery chaired by Jim Hoxie and Dennis Burton; 2) animal models chaired by David Watkins and Malcolm Martin; and 3) Clinical Research chaired by Scott Hammer and Julie Overbaugh. Great press coverage. I concluded at end of meeting that we would indeed turn the knob more towards basic discovery research and promised an immediate $10 Million for a broad RFA to come from moneys saved from truncating some of the clinical trial activity such as a tighter PAVE 100. Recall that our budget has been flat for the past 5 years and so there is no extra money coming in. Below is an article from the NY Times by Larry Altman from Mar. 26 that summarized the Mar. 25 meeting: Rethinking Is Urged on a Vaccine for AIDS By LAWRENCE K. ALTMAN WASHINGTON — Researchers must go back to the drawing board before they can develop an effective vaccine against H.I.V., AIDS experts said at a scientific meeting on Tuesday. And Dr. Anthony S. Fauci, the top federal official responsible for AIDS research, agreed that more fundamental knowledge is needed about H.I.V. and the way the body and experimental vaccines respond to it before the goal of a licensed H.I.V. vaccine can be reached. Dr. Fauci, the director of the National Institute of Allergy and Infectious Diseases, pledged to re-evaluate the use of all $1.5 billion his agency spends on AIDS research to come up with the necessary money. “Everything is on the table,” Dr. Fauci said at the one-day meeting, a Town Hall-type discussion for vaccine researchers on how best to spend federal H.I.V. vaccine money in light of a budget that has been flat for several years. “There is not an immediate solution to the problem,” Dr. Fauci said in an interview. But, he also said, the budgetary constraints mean that “we are going to have to justify what we are doing” and determine what steps to take after further discussions in smaller meetings with researchers. The reassessment comes after last September’s widely publicized failure of what had been the most promising candidate for an H.I.V. vaccine. Many health officials believe that an effective vaccine would be the most crucial weapon in stopping the H.I.V. pandemic. Scientists do not have a full understanding of why the vaccine failed, or why it was possibly harmful, in two large trials in the United States and South Africa. Dr. Fauci’s institute helped pay for the trials of the vaccine, which was made by Merck. Such failures have led a number of scientists to challenge the direction of federal H.I.V. research. On Tuesday, the AIDS Health Care Foundation called for the suspension of money for H.I.V. vaccine research and reallocating resources into effective H.I.V./AIDS prevention, testing and treatment strategies. But Dr. Fauci strongly rejected the proposal. “Under no circumstances will we stop AIDS vaccine research,” Dr. Fauci said at the conclusion of the meeting. Dr. James Hoxie of the University of Pennsylvania echoed the belief of many other participants by saying, “we are not close to having a vaccine” and “there is a tremendous need for innovation” in developing one. Experts at the meeting also said that Dr. Fauci’s agency needed to support efforts to further develop animal models of human H.I.V. The experts also urged greater cooperation between AIDS scientists who work on such animal models and those who are trying to develop an H.I.V. vaccine for humans. A crucial issue is supporting younger researchers to replace the cadre of veteran AIDS scientists, many of whom are working beyond traditional retirement age. Dr. Fauci said a first step would be to pare existing projects to immediately provide $10 million to $15 million for about 30 grants to be awarded to scientists who propose novel ideas. Some of the grants would be used to support young researchers, he said. Some scientists support conducting large vaccine trials in humans before all the fine points of the vaccine research are complete in animals because of the urgency of the pandemic. Others urge caution out of fear that failures could destroy confidence among uninfected people most at risk who would be needed as volunteers in future trials. Equally vocal groups call for testing everything as soon as the research shows promise because of the urgent need for a vaccine. Dr. Warner C. Greene, a co-chairman of the meeting and director of the Gladstone Institute of Virology and Immunology in San Francisco, said he hoped that a century from now, historians looking back on the AIDS pandemic would view Tuesday’s meeting as a turning point.