The AIDS policies of the past are likely
to bring us only slow, fitful progress."
_______Dr. William Paul, Director of the Office of AIDS Research, National Institutes of Health
This past February, William Paul finally admitted what a growing chorus of scientists and community advocates have been saying for years: Research towards a cure has stalled and NIH policies are a key reason.
While some effective treatments and preventives for opportunistic infections have emerged from NIH research (after much activist pressure), Dr. Paul admits that in terms of anti-virals, "people are worried that after protease inhibitors they do not see a very good picture." And with that prelude, Dr. Paul appointed a "blue ribbon expert panel", the NIH AIDS Research Program Evaluation Working Group, to "carry out a comprehensive evaluation of our nation's biomedical research effort against AIDS" and to "set priorities for AIDS research for the next five years."
At a time when hate-mongering Republican Congresspeople are gunning to slash AIDS research funding, it is even more critical that NIH get its house in order. ACT UP not only opposes cutting one penny of the current Office of AIDS Research(OAR) budget, but believes that current federal spending on AIDS research is woefully inadequate for finding a cure rapidly. Any reductions would be a disaster for people living with HIV/AIDS.
Additionally, in 1993 we proposed a five-year $1.84 billion multi-disciplinary AIDS Cure Project,independent of NIH, to explore all promising pathogenesis/treatment approaches in conjunction with existing OAR programs. This detailed plan is now a bill in Congress with 20 co-sponsors.
Unfortunately, Dr. Paul's prescribed remedies for the research dead-end, while mini-steps forward, don't begin to strike at the entrenched roots of the problem. Meanwhile, Dr. Paul continues to reject proposals for doing just that. This is an ominous beginning for what purports to be a fundamental reassessment process.
Understanding AIDS pathogenesis -- the factors and processes leading to disease progression -- is key to finding a cure. Dr. Paul's call for allocating more funding to basic science investigations is an advance which many have advocated for years. But if the grants are given out as they are now, highly promising paths will continue to be blocked. NIH peer review committees dogmatically favor a narrow band of fashionable theories. The lion's share of funds goes to dissecting HIV's functioning;little is allowed for the immune system's response and a range of co-factors -- such as other microbes, nutritional deficiencies and stress -- that may be key to unraveling these mysteries.
Scientists with innovative, dissident theories -- no matter how well supported -- are consistently denied grants and sometimes publicly belittled. In 1990, scientists at the world-renowned Pasteur Institute (whose director discovered HIV) and the respected U.S Armed Forces Institute of Pathology reported strong evidence that a bacteria-like agent called a mycoplasma may play a key role in causing some of the most dangerous immune system damage in AIDS. If true, this could open the door to use of some types of antibiotics. Yet NIH officials, without attempting to replicate the research, denounced it as implausible and refused to devote more than token resources to follow-up.
Under pressure from leading researchers in the field, NIH held a one-time conference in 1993 on HIV Infection and Oxidative Stress (the process of cellular damage caused by free radicals, increasingly recognized as key to many illnesses). Despite strong evidence of important leads to both pathogenesis theory and antioxidant (vitamin/mineral) treatment, and a conference consensus on the exciting potential of this research, Dr. Paul has never allowed a previously-scheduled presentation to the NIH AIDS Executive Committee of proposals for follow-up, and has refused to return the conference chair's phone calls.
Increasing results of epidemiological and clinical studies, combined with neurobiological research, are confirming that the field of psychoneuroimmunology (PNI) -- the biological/hormonal connections between stress, emotions and immune function -- is a key to the pathogenesis of AIDS (and many illnesses). Yet NIH has consistently rejected proposals for larger-scale studies to move our knowledge forward. Last year, Dr. Paul cut all research grants in this field that did not directly focus on AIDS. This despite evidence that underfunding of PNI basic science (like that of other immunology fields which Dr. Paul supports) has left a need for catch-up work that could be extremely valuable in clarifying AIDS' pathogenesis.
A few large drug companies exert inordinate and inappropriate power over the priorities set for NIH's clinical research. For years, a handful of toxic, expensive antiviral drugs -- marginally effective at best -- have monopolized the bulk of the clinical trials budget. This partially reflects the increasing funding by big pharmaceuticals of cash-strapped universities, the source of most members of NIH peer review committees. More directly, outright conflicts of interest abound on the most powerful committees:
"Scientists who have made their entire careers in AZT have sat on committees voting on potential commercial competitors.Scientists who have had financial dealings with Burroughs Wellcome or other pharmaceutical companies have come to dominate the government's entire clinical trials network." -- Bruce Nussbaum, Business Week reporter, author, Good Intentions
NIH has no agency-wide regulations prohibiting conflicts of interest by outside researchers sitting on its decision-making committees. Even a simple disclosure policy has been derailed for five years by the opposition of powerful drug-company-funded investigators who control those committees.
Beyond these specific means of influence, NIH acknowledges that its clinical trial program is institutionally geared almost exclusively toward developing new drugs which can be approved by the Food and Drug Administration (FDA). The result: Thousands of people with HIV/AIDS spend precious funds on already-available treatments showing promise in small studies and clinical reports (often published or presented in mainstream venues). Yet NIH offers little or no research funding to separate the useful from the wasteful or toxic. Virtually ignored are: off-label use of approved drugs, drugs whose patents have expired, drugs owned by small companies unable to afford expensive trials, drugs approved in foreign countries, vitamins, herbs, diet, acupuncture, and low- or no-cost practices like massage, exercise and stress management -- all approaches with minimal or no potential for profit, many of which are unpatentable,thus lacking a major corporate sponsor.
Isn't this just the sort of gap NIH is supposed to fill? This lack of research has surely killed many people with AIDS.
Several epidemiological studies show serious nutritional deficiencies beginning in early HIV infection which speed progression and death. Small treatment studies show value in supplementation. Yet NIH has rejected several thoughtful proposals for clinical trials on vitamins and minerals from medical schools at Johns Hopkins, University of Miami, and elsewhere.
Since 1992, community advisers to NIH have been advocating a substantial-size community-based clinical trial of two widely used and promising antioxidants, vitamin C and beta carotene. A range of scientists affiliated with the Community Programs for Clinical Research on AIDS (CPCRA) have spent years refining the trial design and attempting to gain approval. Yet three years later, after much bureaucratic resistance, NIH has merely a tentative plan for a small, preliminary toxicity (not efficacy) study of vitamin C alone. No start date has been set and there is no guarantee that if there is acceptably low toxicity, this pilot will be followed by a major trial. Beta carotene has been unsupportably dropped altogether. Furthermore, last year, NIH defunded the research sites most involved in developing this and other equally resisted proposals for trials of alternative treatments.
And lest anyone offer the NIH's Office of Alternative Medicine as the answer to this dilemma, that program's microscopic $5 million annual budget is hardly enough to offer more than superficial research on any treatment for any disease.
Dr. Paul is publicly silent on these issues, and indeed perpetuates the conflict of interest problem by appointing drug company personnel and researchers receiving pharmaceutical fees to the evaluation panel and subpanels.
Meanwhile, at a meeting last summer with a broad delegation of community advocates, Dr. Paul specifically rejected even exploring either 1) the funding of clinical trials on promising but neglected treatments in broad community use, or 2) innovative suggestions on clinical trial design. Refusing to exercise his Congressionally-mandated responsibility to examine and remedy gaps in research, he simply referred the advocates to the component NIH institutes -- precisely the ones which have been most resistant to such ideas.
An "old-boy-network" of researchers, most working for either prestigious universities or wealthy private research institutions, gets the vast bulk of NIH funds. Academic pressures for career advancement force many researchers -- regardless of good intentions -- to submit proposals aimed more at enhancing their own or their institution's prestige, facilities and budgets than at creatively probing for solutions to this urgent crisis. Again, the self-perpetuating "peer review" committees ensure the exclusivity of this club. So non-elite "mainstream medicine" researchers are at a disadvantage, and those from scientific fields under- or unrepresented at large medical schools -- such as nutrition and alternative medicine -- lack even the pretense of any "peers" on the panels reviewing their proposals.
One prominent AIDS researcher at a major university received 17 grants simultaneously -- a factory model of research -- ensuring minimal supervision or creativity, and aimed mainly at paying institutional overhead.
While Dr. Paul's call for more investigator-initiated research is a positive step, in that it could help promote more innovative projects, it is unlikely to have much effect as long as the composition of peer review committees remains tightly controlled by a closed circuit. A vast wealth of untapped expertise and new ideas lies in the smaller research institutes and universities (both domestically and internationally) as well as in the diverse communities of people with HIV/AIDS and their advocates.
AIDS, like many illnesses, manifests differently in different populations, and its treatments vary in their effectiveness and toxicity from group to group. Part of this is biological, much is social and economic. Yet NIH still refuses to devote serious effort to such disenfranchised populations as women, people of color, drug users and adolescents (the latter being almost totally ignored). This not only excludes such communities from access to treatments, it also prevents the discovery of valuable scientific information that could help everyone with AIDS.
Even populations which are represented in AIDS research, such as white gay men, are often studied in a social vacuum, ignoring the huge trauma and stress caused by widespread homophobic hatred,intense grief from constant losses, and anger at societal indifference and stigma. In all HIV-positive populations, these factors -- and others such as racism, sexism, poverty, violence, homelessness, and poor access to medical care -- strongly affect infection, progression and survival and must be studied.
It took until last year -- 13 years into the crisis, and after many years of activist protests -- for NIH to fund the first full-fledged study of the natural history of AIDS in women. Its funding is inadequate and it will be many years before there are results.
Enrollment in NIH-funded clinical trials by women, people of color and drug users continues to lag far behind those groups' proportions in the epidemic. Part of this is due to the failure to address tangible obstacles to participation -- such as lack of transportation subsidies, child care, and gynecological care. Yet last year NIH defunded 4 of the community-based trial sites (3 of them in hardest-hit New York City), with the best enrollment rates from those groups. Broad community protests failed to dissuade NIH officials.
Among the most important under-studied populations are long-term survivors and long-term non-progressors. The few studies that have been done are small, narrow (mainly white gay men), and focused largely on viral, immunological and genetic factors, while ignoring the social, psychological, nutritional and treatment factors which preliminary research suggests are key. Many valuable leads may lie here, but again, except for limited work advanced largely by pressure from survivors themselves, NIH has shamefully neglected this fairly inexpensive form of research.
Dr. Paul has not only been virtually silent on these issues, but he has threatened the minimal access to clinical trials now available to disenfranchised populations. In his February Science article conceptualizing the Evaluation Group, Dr. Paul warned against the idea of viewing clinical trials as a source of medical care, rather than simply scientific research. He made it clear that in searching for funds to expand basic science work,he will deeply cut clinical research and will ignore the impact on treatment options for severely affected communities. This is unacceptable, particularly in a society which provides grossly inadequate medical care to the poor.
Dr. Paul knows that NIH regulations prohibit using clinical trial funds to finance primary medical care, so the allegedly inappropriate use of research funds is a non-issue. But clinical trials do provide access to experimental treatments which might prove effective, while also permitting some medical monitoring and referrals to appropriate care for people with HIV/AIDS.
The real issue is what type of treatments are offered. In reallocating funds saved by reducing clinical trials of toxic, marginally effective, already-approved anti-viral drugs, serious consideration must be given to urgently-needed studies of numerous broadly-used treatments with promising evidence but no corporate sponsor.
These points are but a small sample of the avalanche of criticism NIH has received from a broad range of scientists and community advocates. NIH's most frequent response to such challenges is to cry "not enough money." Indeed, more money is urgently needed and could theoretically allow some of these neglected research areas to be addressed. But inadequate funding alone cannot explain the grossly disproportionate expenditure on the types of research -- both viral-focused basic science and anti-viral clinical trials -- which are particularly convenient to large drug companies seeking to market expensive products. Nor can it explain the near-zero funding of any researcher with a dissident theory or innovative treatment, or the extreme neglect of studies of disenfranchised groups. Until NIH addresses these core issues, dramatic progress against AIDS will continue to be blocked.
Dr. Paul has perpetuated all the worst NIH biases in constituting the AIDS Research Program Evaluation Working Group. Prior to ACT UP's intervention, this Working Group and its 6 Area Review Panels specializing in particular research fields, were a mirror image of the well-connected peer review committees at NIH itself.
A few community representatives, representing a narrow band of opinion (most are members of the Treatment Action Group, though also affiliated with other organizations), were included on each committee. Their presence is valid, but in no way can serve as a proxy for the diversity of populations and opinions in the many U.S. AIDS communities, and in any case constitute only one or two voices on each panel of a dozen or more members.
Scientists with innovative ideas not generally recognized were excluded, and entire scientific fields such as psychoneuroimmunology and alternative medicine went totally unrepresented. (Indeed, when questioned by an AIDS Research Center funded by NIH's Office of Alternative Medicine, an OAR official said, "Alternative medicine is not a consideration of the Working Group at this time.")
Until recently, OAR insisted that all meetings would be closed to both the public and media, in probable violation of the Federal Advisory Committee Act.
Shortly after Dr. Paul announced the panel last winter, ACT UP/NY wrote him and panel chair Dr. Arnold Levine, demanding much more diverse scientific and community representation. Since then, a range of community advocates, coordinated by ACT UP/NY and Philadelphia, has met or spoken several times with Dr. Levine, urging open meetings, public hearings in several cities hardest hit by AIDS, ads in major scientific journals soliciting new research directions, and various other measures to maximize input. Most of these proposals have been rejected.
When Dr. Levine refused to carry out a broad public search for panelists, we did it ourselves, making a call on the Internet and elsewhere. As a result, we put forward 30 distinguished, knowledgeable scientists and community advocates representing excluded views or populations. Most of these nominations have been ignored, and Dr. Levine has specifically rejected appointing any expert (no matter how well-credentialed) on alternative medicine, calling that field "too non-mainstream"..
But after months of pressure, we have won these concessions:
"Some of the meetings, or portions of the meetings, will be open and time will be provided for public comments." (Letter from Dr. Paul to ACT UP, 7/7/95)
Late in the process, our nominee for the overall Working Group, Kiyoshi Kuromiya, Editor of Critical Paths AIDS Project Newsletter, member of numerous NIH advisory councils, ACT UP/Philadelphia spokesperson and a Japanese-American person with AIDS, was appointed. Two of our 30 nominees to the Area Review Panels were appointed:
Bruce Rabin, Professor of Pathology and Psychiatry and Director of the Brain, Behavior and Immunity Center at the University of Pittsburgh -- to the Pathogenesis/Etiology Panel
Ferd Eggan, Los Angeles City AIDS Coordinator, long-time community advocate and a person with HIV -- to the Behavior and Social Science Research Panel.
These decisions, while small steps in the right direction, are far too minor to fundamentally change the skewed and secretive nature of the review process. Unless our full list of demands are met, OAR's professed commitment to a searching, top-to-bottom re-evaluation of AIDS research will remain the sham that it is today.