HIV/AIDS – a disease named, research continues

August 2006

By the end of 1981, the CDC realized it was dealing with a unique, fast-spreading disease when cases of opportunistic infections, specifically Pneumocystis carinii pneumonia (PCP) and Kaposi’s sarcoma (KS), appeared in gay men. However, shortly thereafter, as the New Year approached, this disease of unknown origin began crossing the bounds from the gay community into heterosexuals.

In 1982, health officials detected cases in other populations, specifically intravenous drug users, hemophiliacs and blood transfusion recipients among men and women of all ages. Opportunistic infections were spreading well beyond just the small cluster of patients in the enclaves of the gay community in New York City’s Greenwich Village, San Francisco’s Castro District and pockets of Los Angeles. This disease was no longer exclusively a “gay disease.”

“Not everyone was aware of how this thing was exploding before our very eyes. When it spread beyond the gay population, that’s when people realized this disease had became something that was not just someone else’s problem,” said Anthony S. Fauci, MD, chief of laboratory immunoregulation at NIAID and an infectious diseases and immunology researcher at the NIH.

Disease surfaces among others

At a CDC Task Force on Kaposi’s Sarcoma and Opportunistic Infections meeting, Bruce Evatt, MD, head of hematological diseases at the CDC, announced that an elderly man in Florida who had hemophilia developed PCP and died. Health officials went to the man’s home and conducted a medical investigation. Several more cases among hemophiliacs began to appear shortly after, and researchers realized this was not the first one.

Once this disease was found to be in the blood supply, people became much more concerned that anyone could be at risk, according to James W. Curran, MD, PhD, then chief of the Venereal Disease Research Branch at the CDC and chair of the Task Force. Other groups began to acquire this disease: Haitians, prostitutes, women who had sex with bisexual men and even children.

“It appeared to be much more widespread and now was not being limited to homosexual men, drug users or even heterosexual transmission,” said Curran, now dean and professor of epidemiology and medicine at the Rollins School of Public Health at Emory University and director of the Center for AIDS Research. “We became very concerned about the safety of the blood supply. People caring for patients became afraid and fear in the public led to more discrimination.”

Some hospitals in New York City and San Francisco had 25% to 40% of the entire ward occupied by sick, dying patients, whereas in other parts of the country, people rarely saw an infected individual. What made these cases unique was the fact that these patients did not suffer from KS; only gay men who acquired this disease through sexual transmission developed KS.

“The staff at the NYU blood center were overwhelmed and there was fear of transmission through blood and blood products,” recalled Alvin E. Friedman-Kien, MD, professor of dermatology and microbiology at New York University Medical Center.

By the end of the year, health officials reported an estimated 771 AIDS cases to the CDC, 618 of which ended in death, according to the American Foundation for AIDS Research (amFAR).

“When it was detected in hemophiliacs, gay and straight people and injection drug users, it became quite clear that it was probably caused by an underlying virus,” Curran told Infectious Disease News. “Then the questions turned. What is the virus and when would it be discovered?”

Investigation continues

Interest grew to investigate the underlying causative factors associated with this disease. Friedman-Kien and colleagues applied for a grant from the NIH but were originally rejected because of a lack of a hypothesis. Researchers didn’t know where to begin; all they could do was continually gather data.

“Unfortunately it was a disease of the underdog,” he said. “Everyone was desperate because we had no clue as to what was happening.”

The CDC brought researchers together and held meetings in various locations to try to accrue data. Researchers across the nation were intellectually and emotionally challenged by this disease and spent long hours and numerous days conducting research to better understand this illness. Laboratories across the nation began detailed investigations; some lacked funding to conduct adequate research, some lacked specific tools needed to make a connection between the cases of PCP originally seen in Los Angeles and cases of KS identified in New York City and San Francisco, and others had the resources needed.

“We had the laboratory resources and could work it up,” said Michael S. Gottlieb, MD, assistant clinical professor of medicine at the University of California at Los Angeles School of Medicine.

“In those days general physicians or infectious disease physicians were not as focused on T-cell host factors, but we were able to connect the dots,” said Gottlieb, lead researcher of the original Morbidity and Mortality Weekly Report that published the first case descriptions. “An oncologist or dermatologist saw KS and an infectious disease doctor saw infections, but we saw both and associated this disease with immune deficiency.”

Meanwhile, Fauci was conducting research on the relationship between infectious diseases and the human immune system when he decided to turn his attention to this “new, yet undescribed evolving disease”.

“I assumed that it was a new infection, even though I, like everyone else, had no idea what this new infection was,” said Fauci, now director of the National Institute of Allergy and Infectious Disease.

Fauci and colleagues admitted patients to the ward at the NIH. Symptoms consisted of all of the complications associated with a totally destroyed immune system, mostly opportunistic infections and to a lesser extent KS. Over ensuing months, researchers realized that the disease was sexually transmitted and transmitted by blood and blood products, as well as by contaminated syringes/needles involved in illicit drug use.

“There was no indication of why there was this common thread among these distinct groups,” he said. “The epidemiological pattern of it told me it was primarily an STD. It worried me that we were dealing with a disease that was spread by a very universal human activity, namely sex, that was deadly in its consequences.”

Researchers had several unanswered questions to resolve, first and foremost, what was causing these illnesses. Once that became clear, the next big breakthrough was the development of a diagnostic test to screen the blood supply for transfusions and to do sero-surveillance studies to monitor infection rates.

“It started off as a very unusual, curious observation, which then began to unfold in a very rapid way over periods of months to a year until the patterns of transmission became clear and ultimately the etiologic agent was identified,” Fauci told Infectious Disease News.

AIDS is born

In July of 1982, after people began to realize this disease was no longer limited to gays and Gay Related Immune Deficiency (GRID) was now an inaccurate term to describe this disease, the CDC and NIH officials, joined by university researchers and members of activist and nonprofit organizations, gathered at the HHS building in Washington and coined the disease as Acquired Immune Deficiency Syndrome, or AIDS.

“It was reasonably descriptive. We felt it was quite clear then that this was a syndrome that was acquired and that underlying immune deficiency was the common factor,” Curran said. “We thought that it was quite likely caused by an infectious agent, but one that had not yet been found.”

All agreed that the disease was acquired, not inherited, resulted in deficiency within the immune system and was a syndrome with a number of manifestations. By August this newly described name was recognized in newspapers, academic journals and elsewhere.

But even with a name in place, little knowledge still existed about the syndrome. Researchers around the globe would go on to investigate AIDS and see that it was a silent global killer that was actually present beyond the United States before this time. They would also ultimately discover the virus that causes AIDS, as well as treatment methods to help people living with the disease live longer, healthier lives and methods of reducing the risk of transmission to others.

“Initially it was the discovery of the epidemic and the excellent case definition and surveillance that defined the epidemiologic patterns and led to prevention recommendations well before the virus was even discovered so that the blood supply could be protected and health and laboratory workers and people like gay men could be protected from further spread of the disease,” Curran said. “Surveillance was the most important thing early in the epidemic, and good surveillance continues to be very important in the United States and throughout the world.”

Glance at HIV/AIDS today

The CDC’s quick response to an initial known outbreak of PCP, which consisted of five cases within eight months in Los Angeles, was an example of the extraordinary efforts health officials took to recognize and respond to anew threat to public health.

“The CDC staff has played an important role in identifying the roots of transmission, quickly informing and educating the public about transmission and protection, providing guidance on HIV counseling and testing, protecting health care workers, creating partnerships with national organizations, health departments and community organizations that implement evidence based prevention programs,” said Kevin Fenton, MD, PhD, director of the CDC’s National Center for HIV, STD, and TB Prevention.

National efforts have elicited a number of important results, according to Fenton. First, the number of annual infections has declined sharply from an estimated 150,000 new diagnoses at the height of the epidemic in the 1980s to 40,000 infections in recent years. Annual injection drug user’s infection rates also declined in the 1990s and are currently less than 2%. Mother-to-child transmission in the United States has declined dramatically, Fenton said, from a high of 2,000 children born with HIV per year in the mid 1990s, down to an estimated 300. Surveillance methods have improved, with 43 states initiating confidential name-based diagnosing and the CDC implementing a nationwide system to more accurately diagnose infections.

“In the history of medicine, we’ve never had such a situation like AIDS where a new disease appeared of unknown origin, the causative agent is discovered and a treatment is suddenly available that was never available for any viral infection,” Friedman-Kien said. “I think the progress made has never been surpassed by any other research. What has been gained in understanding virus replication and antiretroviral treatment had far-reaching effects for every other disease we deal with.”

However, 25 years into the epidemic, prevention is still the only cure for AIDS. Although prevention efforts have saved countless lives, the changing U.S. epidemic continues to pose new challenges.

In 2004, 16,000 Americans died of AIDS, according to the CDC. More than 1 million Americans currently live with HIV/AIDS, 25% of whom are still unaware of their status. Blacks are hit hardest, specifically black men who have sex with men. In 2004, women accounted for 29% of all diagnoses.

“We have learned over the last 25 years that HIV prevention is not easy. It requires a life long commitment from everyone, from those infected, those at risk and from society as a whole,” Fenton concluded at a CDC press HIV/AIDS teleconference. “At home and abroad we must continually step back and evaluate what is working and what is not. We must advocate for prevention resources to keep pace with the epidemic. We must be bold in our actions and fight complacency at every turn.”

For more information:

• Fenton K, Curran JW, et al. CDC 25 years of AIDS. CDC teleconference. May 5, 2006.
• CDC. Pneumocystis pneumonia – Los Angeles. MMWR. 1981;30:250-252.
• CDC. A cluster of Kaposi’s Sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and orange Counties, California. MMWR. 1982;31:305-307.
• http://aidshistory.nih.gov.