This first-person account by one of the pioneers of HIV/AIDS research chronicles the interaction among the pediatric HIV/AIDS community, regulatory bodies, governments, and activists over more than three decades. After the discovery of AIDS in a handful of infants in 1981, the next fifteen years showed remarkable scientific progress in prevention and treatment, although blood banks, drug companies, and bureaucrats were often slow to act. 1996 was a watershed year when scientific and clinical HIV experts called for treating all HIV-infected individuals with potent triple combinations of antiretroviral drugs that had been proven effective. Aggressive implementation of prevention and treatment in the United States led to marked declines in the number of HIV-related deaths, fewer new infections and hospital visits, and fewer than one hundred infants born infected each year.
Inexplicably, the World Health Organization recommended withholding treatment for the majority of HIV-infected individuals in poor countries, and clinical researchers embarked on studies to evaluate inferior treatment approaches even while the pandemic continued to claim the lives of millions of women and children. Why did it take an additional twenty years for international health organizations to recommend the treatment and prevention measures that had had such a profound impact on the pandemic in wealthy countries? The surprising answers are likely to be debated by medical historians and ethicists.
At last, in 2015, came a universal call for treating all HIV-infected individuals with triple-combination antiretroviral drugs. But this can only be accomplished if the mistakes of the past are rectified. The book ends with recommendations on how the pediatric HIV/AIDS epidemic can finally be brought to an end.
|Publisher:||Vanderbilt University Press|
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About the Author
Arthur J. Ammann, MD, Clinical Professor of Pediatrics at the University of California, San Francisco, is the founder of Global Strategies, an organization dedicated to empowering communities in the most neglected areas of the world to improve the lives of women and children through health care. His pivotal research studies on vaccines resulted in the first FDA approval of a pneumococcal vaccine for infants, children, and the elderly. In 1982 Dr. Ammann described two of the three ways that HIV is transmitted: from mother to infant and from the transfusion of blood. He is the recipient of more than fifty national and international awards.
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The Unneccessary Deaths of Women and Children from HIV/AIDS
By Arthur J. Ammann
Vanderbilt University PressCopyright © 2017 Vanderbilt University Press
All rights reserved.
A MYSTERIOUS NEW DISEASE
It was June of 1981 when the scientific and medical communities first read about a mysterious new immunodeficiency disorder seen in young gay men (Gottlieb et al. 1981). The disease was first reported by Dr. Michael Gottlieb, a physician and immunologist at UCLA, who had identified a number of previously healthy young men who had suddenly developed a variety of opportunistic fungal, viral, and protozoal infections. The infections were of varieties not typically observed in adults, except in cancer patients whose immune systems had been suppressed after receiving large doses of radiation or chemotherapy. The young men whom Gottlieb was treating, however, had no history of cancer or cancer treatments. Gottlieb's initial report created quite a stir, and it soon became apparent that similar cases were on the rise across the country, from Miami to New York City to San Francisco. Due to its prevalence among young gay men, some clinicians initially termed the disease Gay-Related Immunodeficiency, or GRID. In 1982, however, a group of activists and the US Centers for Disease Control and Prevention (CDC) suggested that the name "AIDS" be used instead, and the name stuck.
I knew Michael from the immunology circles that we each traveled in — rather small circles, as there were few immunodeficiency diseases known, except in children, where we were dealing with genetic immunodeficiency disorders on the order of about one in one hundred thousand. Michael's patients were adults, and what he was describing was a severe immunodeficiency in previously healthy individuals. Michael was not prone to exaggeration, so when I read news reports about this new disorder in young gay men, I took it seriously, even though I could not conceive at the time that it had anything to do with children and immunodeficiency disorders.
When the news broke, I was working as a professor of pediatric immunology at Moffitt Hospital at the University of California San Francisco (UCSF) Medical Center, where I had established the first immunology laboratory devoted to the study and diagnosis of genetically acquired immunodeficiencies in both children and adults. There would be an occasional adult with a disease called acquired hypogammaglobulinemia, but this was a genetic disorder that could be easily diagnosed and treated. Much of my laboratory's activity focused on performing immunologic tests, especially measuring patients' levels of T-cells (TDL) — which are derived from the thymus gland and bone marrow and are known to protect against opportunistic infections — and B-cells, which produce antibodies of different types, collectively known as immunoglobulins, against bacteria, viruses, protozoa, and fungi. My laboratory studied a number of rare immunologic disorders in children, including Ataxia Telangiectasia, Wiskott-Aldrich syndrome, and congenital hypogammaglobulinemia. The most severe disorders were typically characterized by deficiencies in both TDL numbers and function, as well as decreased levels of immunoglobulins. These severe but rare disorders had not been known to occur in formerly healthy adults. However, in 1981, there were increasing numbers of reports added to Gottlieb's groundbreaking discovery, and they were coming from major metropolitan areas in the United States. They had in common severe acquired immunodeficiency, occurring almost exclusively in young gay men who had no apparent cause for the disorder. AIDS appeared to be a new immunodeficiency disorder far removed from any of the forms of immunodeficiency that I had been studying for more than a decade.
During my first ten years on the faculty at UCSF, I had established an immunology laboratory to assist in diagnosing the patients who were referred to me for possible immunodeficiency disorders. In the process I discovered several new immunodeficiency disorders that were unknown, not only to the pediatric community, but also to the general medical community. Thus, in August of 1981, I was not completely surprised when I was invited to a meeting of fellow UCSF faculty members to discuss the strange new immunodeficiency disease that seemed to be spreading among young gay men nationwide.
The discussion group was called together by Dr. Marcus Conant, a dermatologist who was seeing an increased number of patients with Kaposi's sarcoma (KS), a rare cancer that classically occurred in middle-aged men of Mediterranean descent but was now being observed with increasing frequency in the newly described AIDS disease (CDC 1981a). The group, which met regularly for lunch at the UCSF Faculty Club, was made up of an eclectic mix of individuals from various departments. Considering the significance of what was happening, and how this entirely new disease would move from a handful of patients to a major worldwide epidemic, the beginnings of the discussion group now seem inauspicious.
On November 6, 1981, Dr. Conant sent the ad hoc group a memo outlining the immunologic studies of the disease, which would be performed in my laboratory. I truly believed at that time that the number of patients who required studies would be limited, but I also felt it was important to document the degree of immunodeficiency and agreed to include a repository of blood samples from all patients suspected of having the acquired immunodeficiency. Thus began an organized approach to the evaluation of suspected AIDS patients, laying the groundwork for a repository of blood samples that, following the discovery of the human immunodeficiency virus (HIV) in 1983 as the cause of AIDS, would be tested to prove that the 1981 patients, many of whom had died by 1983, were indeed infected with HIV (Barre-Sinoussi et al. 1983; Broder and Gallo 1984; Chermann et al. 1983; Gallo et al. 1983).
From the very beginning of the Faculty Club meetings and throughout the early years of the AIDS epidemic, the original members of the ad hoc group worked collaboratively to define the epidemiologic, clinical, and laboratory features of AIDS, and from that point forward all members of the group would dedicate their professional careers to the AIDS epidemic. It was an extraordinary time of collaborating between individuals from different medical disciplines, gradual piecing together of different presentations about AIDS, and unraveling of a mystery that would eventually be attributed to a single cause.
I particularly remember Paul Volberding, an energetic young research fellow in hematology and oncology, who was looking forward to an exciting career at UCSF. His AIDS patients began coming to him in increasing numbers with a variety of hematologic problems as well as KS. Paul had the essential combination of interest in pursuing the cause of disease coupled with compassion for the patients he saw, almost all of whom were deteriorating before his eyes due to immunodeficiency complications. It was not surprising that Paul was not only a key player in documenting the efficacy of one of the first drugs to treat HIV but also the individual who formed one of the first compassionate and comprehensive AIDS clinics in the United States to address the emerging epidemic (Fischl, Richman, Grieco, et al. 1987; Groopman and Volberding 1984).
Marcus Conant was a dermatologist with a large and thriving dermatology practice in San Francisco and at UCSF. As I got to know Marcus, I was impressed with his tenacity and determination to go beyond just the dermatologic manifestations of his patients to try to get at the cause. Marcus also seemed well connected politically, and I learned that he would use his political influence to be certain that AIDS was not ignored, either by the medical community or politicians. Marcus had started to observe a marked increase in the number of patients suffering from KS who were not of classical origin, middle-aged men of Mediterranean extraction. Instead, these were young men who were referred to him to evaluate lesions that were appearing on the skin, mouth, and esophagus and which could have metastasized to other areas of the body.
William Wara, a radiation oncologist, joined the group because he, too, was observing an increasing number of patients with malignancies, ranging from KS to unusual lymphomas. His medical experience broadened the spectrum of the subspecialties in which patients with AIDS were being seen and highlighted the association of immunodeficiency and malignancy.
John Greenspan was an oral biologist who was observing a dramatic rise in the number of young gay men coming to his clinic with oral lesions called oral hairy leukoplakia, a relatively rare disease causing lesions on the mouth and tongue. John brought flair to the group with his distinct English accent but, more importantly, he broadened the spectrum of AIDS as he and his collaborators persisted in defining the various manifestations of the disease, eventually discovering the association of Epstein-Barr virus (EBV) with hairy leukoplakia (D. Greenspan 1985; J. S. Greenspan et al. 1985).
We continued to meet almost weekly, each of us consciously realizing that as more and more individuals were reported with AIDS, we were participants in the evolution of a new disease. On occasion, and with some trepidation, we would speculate as to whether the epidemic might expand to other populations and other countries. In this way the meetings became almost prophetic as questions of "What if this were to happen?" were soon answered with ever-increasing reports of new populations manifesting the clinical and laboratory features of AIDS. But in those beginning days of the AIDS epidemic I felt somewhat removed, thinking that this new disease was confined to young adult males and could not occur in infants and children. My role remained to document the immunologic profile of this new disease and to process how such a disease could occur and whether it would remain confined to a specific population of individuals in the adult community.
The challenges that lay before our group seemed urgent, and it was perhaps for this reason that we never paused to establish an official name. As we continued to discuss the evolution of this mysterious disease that was fast becoming a major epidemic, the effort to find a common etiology among all of the patients increased. The growing number of individuals who required immunologic evaluation was beginning to put pressure on my laboratory. Nevertheless, I agreed to offer the immunologic tests to assist in identifying and following patients who were being diagnosed with AIDS.
During the months that followed, concern about the increasing numbers of young gay men with AIDS came from many different individuals in the medical field. On March 22, 1982, a meeting was called at San Francisco General Hospital, where many of the AIDS patients were being evaluated. The University of California was not receptive to having these patients at their main hospital on "The Hill," as we often referred to the medical center. They feared that if referring physicians knew that individuals with AIDS were being admitted to the University hospital, they might not refer other patients. The meeting at San Francisco General was with Drs. Volberding, Wara, Drew, Sande, Gerberding, and me, all of whom were drawn into the AIDS epidemic either because we were seeing patients or because we were seeing the complications of AIDS. This particular meeting was the beginning of the attempt to precisely define the extent of the problem. Did it involve, for example, only the gay community? And how did the other risk factors that were being observed, such as KS, fit into the picture of the acquired immunodeficiency syndrome? At this early stage of the AIDS epidemic, it was clear that patients were presenting with very advanced immunodeficiency and primary clinical manifestations of opportunistic infections. Were there earlier manifestations of the syndrome?
FUNDING EMERGES FOR HIV/AIDS RESEARCH BUT NOT WITHOUT CONTROVERSY
Early in the epidemic there was a paucity of funds to conduct research into the cause and treatment of HIV/AIDS. I was a professor of pediatrics and immunology at the UCSF Medical Center in charge of the Pediatric Clinical Research Center, which gave me a limited amount of flexible funding to investigate immunodeficiency disorders in children. I had established a laboratory that had the capacity to measure all aspects of immune function. It was this laboratory that was called upon to do the first immunologic studies in both adults and children who presented with AIDS in 1981 (Ammann, Abrams, et al. 1983; Ammann 1983; Weintrub et al. 1983).
I was not the only one struggling with obtaining funds to conduct research into this new syndrome primarily affecting gay men in San Francisco. Depending on which clinical presentation of AIDS caused patients to seek medical help, they were referred to specialists in infectious disease, hematology, oncology, oral biology, or dermatology — each of the doctors in these subspecialties needed funds for research. The problem was that there were no funding agencies that foresaw the impact of the AIDS epidemic, and they were reluctant to invest funds in a new disease.
Dr. Marcus Conant was seeing a dramatic increase in patients with AIDS and KS in his dermatology office at UCSF, and he wanted to know if there was a relationship between KS and HIV/AIDS. Conant had direct access to Willie Brown, Jr., who at that time was the head of the California state legislature. Brown was sympathetic to funding AIDS research, and he decided to gather together the clinicians who were seeing patients with AIDS, including myself, as I was now seeing children with the same disorder. A masterful politician, Brown felt he could get state funding for research on AIDS — but he needed a detailed research plan from those immersed in the California epidemic.
In May 1983, Willie Brown called for a meeting in his office in Los Angeles and invited investigators from the University of California, San Francisco, Los Angeles, and Irvine to put together a comprehensive research proposal with the anticipation that state funding would be available. Those from UCSF included Drs. Conant, Volberding, Greenspan, Levy, and I. We left San Francisco on a 5:30 a.m. flight to Los Angeles. When we arrived, we worked intensely, with Conant as the leader. Sometime during the middle of the meeting, Willie Brown entered the room and in his eloquent way outlined the importance of what we were doing and what else needed to be done. We could only sit in amazement at his political prowess. Apparently, he had already announced to the press that he was going to give money for AIDS research, even though it had not officially been approved by the state legislature. It was a great political move. Even if the money was never made available, he would still get the credit for making the move to provide the first state funding for AIDS research.
It wasn't long before others in the university system found out about the availability of special funding through Willie Brown. They were extraordinarily upset that a small group of upstart investigators would have the audacity to go straight to the legislature to obtain funds for AIDS research. Accordingly, they decided that the money would not go directly to the investigators but would instead go through what they called "The Cancer Coordinating Committee," a group with no experience in AIDS research and composed of individuals who seemed more intent on slowing the funding process than in making research money quickly available.
In the end, Willie Brown put together a $2.9 million package of state funding to compensate for the lack of federal funding for AIDS in California. The legislature approved the total amount, and California Governor George Deukmejian signed the bill in October. But the University of California hierarchy, including Dr. Rudi Schimd, Dean of the UCSF Medical Center, allowed the funds to languish in the coffers of the Cancer Coordinating Committee. When the committee was criticized by the AIDS community, they responded by fabricating reasons that they hoped would satisfy the public. Cornelius Hopper, who was the assistant to the University of California president, said that the delays came about because the researchers did not submit detailed enough proposals ... academic politics had nothing to do with the decision, and they planned to disperse the money by November 30th, a whole six months after the meeting in Willie Brown's office in Los Angeles. Speaker Brown was furious with the university and asked for an investigation of the delay. He stated, "California has a public health emergency and these funds are critical if existing AIDS research is to continue ... the university's bureaucrats must stop treating these funds as gravy to be ladled out to ambitious faculty members who suddenly see a professorship or Nobel Prize lurking somewhere in the tragedy of AIDS."
Excerpted from Lethal Decisions by Arthur J. Ammann. Copyright © 2017 Vanderbilt University Press. Excerpted by permission of Vanderbilt University Press.
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Table of Contents
The First Period: From Discovery to Solutions, 1981 to 1996
Part 1 The Beginning 1
1 Pediatric HIV/AIDS 3
2 AIDS and Blood 13
3 The Blood Banking Industry in Denial 17
4 A Personal Tragedy 23
5 Finding the Cause of AIDS 29
6 Saving Lives: Preventing HIV Infection of Infants 34
7 The Denialist Movement 40
Part 2 Pediatric AIDS Becomes a Reality 51
8 Born of Necessity: The Pediatric AIDS Foundation 53
9 A Priority at Last: Pediatric HIV/AIDS 63
10 A Living Legacy: Elizabeth Glaser Scientist Awards 79
11 The Ariel Project: The Best, the Brightest, and the Committed 84
12 Too Urgent to Wait: The American Foundation for AIDS Research 90
13 What about the Rest of the World? The First Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants 99
14 Ensuring That Voices from Low-Income Countries Are Heard 105
15 A Call to Action: The Second Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants 110
16 Now Just Go and Do It: The Third Conference on Global Strategies for the Prevention of HIV Transmission from Mothers to Infants 121
17 From a Small Beginning to Major Prevention and Care Programs 135
18 Why Wait? Start Now 152
19 Going the Last Mile: The Obscure, the Neglected, and the Desperately Needy 160
Part 3 Unexpected Obstacles: Institutions, Therapeutic Denialism, and Treatment Guidelines 163
20 Pediatric AIDS and Drug Development 165
21 Acronyms and Legislative Redundancy 176
22 Facts Speak Louder Than Words: Examining Efforts That Failed 181
23 Guidelines Can Become Rules 191
24 Treatment Guidelines: Not without Risks 200
Part 4 Stalled: Losing Sight of the Mission 209
25 Damn the Ethics, Full Speed Ahead 211
26 The Tyranny of Research 220
27 Misspent Dollars 233
28 For Better or for Worse? The Pediatric AIDS Clinical Trial Group Expands 242
29 Turning the Corner 246
Part 5 Ending the Pediatric HIV/AIDS Epidemic 253
30 What Went Well 255
31 PEPFAR to the Rescue 265
32 Solutions 272
Timeline: Pediatric HIV/AIDS Milestones and Events 297