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At medical centers across the U.S., confusion and concern were mounting. Young, previously healthy men were presenting with infections and rare diseases traditionally only seen among the immune-compromised, including Pneumocystis carinii pneumonia, extensive candidiasis, and Kaposi’s sarcoma. The cases did not appear to be directly linked to each other.
In December of 1981, the Journal published three articles on this newly observed clinical problem. Dr. Frederick Siegal et al. reported four cases of homosexual men developing chronic perianal ulcerative herpes simplex lesions. Dr. Henry Masur et al. reported 11 cases of community-acquired Pneumocystis carinii pneumonia occurring between 1979 and 1981. And Dr. Michael Gottlieb et al., in an article titled “Pneumocystis carinii Pneumonia and Mucosal Candidiasis in Previously Healthy Homosexual Men,” suggested that the observed syndrome represented “a potentially transmissible immune deficiency.” These original articles, along with later published reviews, are now available online from the NEJM Archive.
Competing theories of disease were proposed, encompassing a wide range of suspected causes. These included amyl nitrite, a prescription drug; isobutyl nitrite, a room deodorizer; repeated exposure to another’s sperm; and general immune fatigue, just to name a few. Physicians noticed that many affected patients seemed to share certain attributes – homosexuality and drug use, for instance, were frequently observed – but the relations between these factors and the disease were unclear. Masur et al. suggested that homosexuals and drug abusers might be “at high risk” for infection; Siegal et al. posited that homosexual men had “a latent, broad-based cellular immunodeficiency that becomes clinically manifest only because of heavy exposure to certain pathogens in particular combinations.”
Because of both its severity and the mystery that surrounded it, the disease that we now know as Acquired Immune Deficiency Syndrome (AIDS) profoundly changed medicine and society, stirring controversy, fueling fear, and claiming millions of lives. Gottlieb wrote in a twenty-year retrospective article published in 2001, “From the very first days, AIDS was a polarizing issue and one that society and its institutions – including academic medicine – were reluctant to take up. […] Discussions of public health strategies to contain the disease aroused anxiety in the homosexual populations about possible draconian measures.”
Patients were not the only ones to be affected by the disease; AIDS changed how many physicians conducted their practices. Gottlieb recalled, “At teaching hospitals, the directors of residency programs worried that having large numbers of patients with AIDS on their wards would make it more difficult to recruit the best applicants. Some clinicians feared for their own safety in caring for patients with AIDS; indeed, the denial of care was not unusual.”
As AIDS became more common, physicians had to continually face the pain of losing their patients to the disease. Gottlieb wrote, “For me and many other doctors, the experience of seeing so many patients die was numbing. […] In 1981, I had no idea how those five patients would change the course of my career and my life.”
Many obstacles stood in the way of developing good treatment options for AIDS. First, the causative agent had to be determined. There was growing evidence to suggest that the source of the disease was viral, but many challenged this hypothesis. A few years following the discovery of AIDS, human immunodeficiency virus (HIV) was identified and confirmatory studies were performed, supporting the idea that the retrovirus lay at the root of AIDS. Tests for HIV detection were subsequently developed and licensed.
Yet even after the therapeutic target was defined, developing effective treatments proved more difficult than anticipated. “AIDS – The First 20 Years,” a retrospective review published in 2001, described this struggle, from the grim failures of early attempts to the first glimmer of hope brought by highly active antiretroviral therapy (HAART). HAART revolutionized treatment for many patients, but as the article pointed out, the AIDS epidemic continues to spread, devastating lives and infrastructure in its wake, particularly in developing countries with minimal or no access to antiretroviral therapy.
Today, AIDS continues to claim millions of lives worldwide, and the search for effective treatment and vaccines continues. In reflecting on how this journey started, it is natural to wonder where it will go from here. What progress will be made toward developing more effective AIDS treatments and delivering them to populations in need? And, given how dramatically the way we think about AIDS has evolved from 1981 to today, is it just as likely that our understanding of the mechanisms driving other complex disease states such as cancer or coronary disease will fundamentally change in the years to come?