HIV/AIDS – unfolding cases of an escalating, rare cancer

July 2006

On June 5, 1981, the Morbidity and Mortality Weekly Report contained the first case descriptions from University of California at Los Angeles researchers of several unexplainable illnesses that would become known as AIDS. All that was known was that all five cases occurred in young, gay men living in Los Angeles who had Pneumocystis carinii pneumonia (PCP) and lab tests indicating T-cell immune deficiency.

Prior to the June 5th report, the CDC noticed an unusual number of orders for a drug called pentamidine isethionate, used to treat PCP. At two of the CDC’s national sexually transmitted disease (STD) conferences, held in San Diego and Atlanta, James W. Curran, MD, PhD, then chief of the Venereal Disease Research Department at the CDC, and colleagues then learned that there were other similar rare, life-threatening opportunistic infections and cancers forming in gay communities across the nation, namely San Francisco and New York City.

“It was more than the rampant enteric diseases and hepatitis and STDs in the gay community,” he said in a National Institute of Health interview published in a document called In Their Own Words .

Some patients were suffering from PCP, and others from Kaposi’s sarcoma (KS); a rare cancer not generally seen in young, otherwise healthy men.

“After the first five cases of pneumocystis were reported, we began to both receive and make additional calls to colleagues in California, New York, and elsewhere,” 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.

Task force formed

Immediately after publication of the first MMWR, CDC researchers from the cancer, parasitic diseases, STDs and viral disease divisions met to discuss what these cases meant and the next steps to take.

In the preceding five years, the CDC dealt with two other major epidemics; Legionnaire’s disease and toxic shock syndrome, Curran explained.

CDC officials decided to form a new task force, comprised of EIS officers and CDC officials that would be called the Task Force on KS and Opportunistic Infections. Curran was elected chairman.

“The first thing we did was to form the task force and come up with a case definition,” Curran told Infectious Disease News. “It was defined as these life-threatening opportunistic infections or Kaposi’s sarcoma in people with no recognized cause of underlying immunosuppression.”

During the initial task force meeting, a call came in from New York City describing some 20 unusual cases of KS at New York University Medical Center. About a week later, Curran and Dennis Juranek, DVM, of the division of parasitic diseases at the CDC, flew to New York to follow up on these case reports.

Meanwhile, the CDC started reviewing the pentamidine isethionate requests. From this, they identified a few more PCP cases in New York, California and one in Atlanta. The CDC began a very active surveillance of 18 of the largest U.S. cites and immediately sent EIS officers to university hospitals and academic centers in these cities to review pathology records, medical records or tumor specimens for any cases of cancer or opportunistic infections dated from 1975 onward; however, no new cases were found.

NY cases

In New York, Curran and Juranek met with Alvin E. Friedman-Kien, MD, professor of dermatology and microbiology, and Linda Laubenstein, MD, assistant professor of medicine, both at New York University Medical Center, who had a patient with KS – an actor from Detroit.

“I recall walking into New York University Medical Center and meeting a man who was almost precisely my age … with what I thought initially was a rare skin cancer that frankly I had never heard of until the week before,” he said during a CDC press teleconference. “As I got to know him, watch his health decline and see him eventually die over the next couple of months, I realized it was a virus that really separated us and a virus that none of us could have really known about.”

Unbeknownst to many, at the time of the first MMWR publication by Michael S. Gottlieb, MD, then an assistant professor of medicine at University of California at Los Angeles School of Medicine, Friedman-Kien had been seeing KS in a number of men in New York City.

Friedman-Kien reflected back on his first patient that would be diagnosed with AIDS; a young man with KS around December 1980.

“It was a disease that prior to this case I had rarely ever seen except in elderly men of Eastern European and Mediterranean origin,” he said. “Suddenly I began to see cases in young men, one then two, then a third one with purple spots on their skin, which when I biopsied them proved to be KS, a disease you rarely ever saw in young people.”

The only unifying factor among his patients was that all three were young, sexually active gay men.

“My initial diagnosis was they were immunocompromised individuals perhaps due to a virus, drugs, or perhaps to multiple STDs,” he said. “In the early 60s there was this big thing ... called Sexual Freedom. Lots of people got STDs like syphilis and gonorrhea, which we thought might be diminishing their immune system.” Sexual Freedom was a movement in Greenwich Village where the gay community banned together.

Concerned, Friedman-Kien contacted members of a local gay physicians’ organization to see if anyone else had similar cases. About three weeks later, he discovered another eight or nine similar cases, and then two more followed.

“In a period of about two months, by mid February or March of 1981, we had 20 cases in New York City,” he said.

Laubenstein had seen two cases at Bellevue Hospital and at the Veterans Hospital, in New York City. Both of her patients died of various opportunistic infections. She noted that one of the patients had a partner who frequently visited one of her dying patients. The partner, Gaten Dugas, was a French Canadian airline steward and had been recently diagnosed with KS. Friedman-Kien then met with Dugas.

“At this point, we had all these cases appearing with a rare disease we had not seen,” he said.

Dugas told Friedman-Kien and Laubenstein about two or three other sexual contacts he had who all died of PCP or other opportunistic infections, all of whom were gay men who lived in the same house together on Fire Island.

Friedman-Kien decided to call an old colleague in San Francisco, Marcus A. Conant, MD, then a dermatologist in a private practice, to discuss the cases. Conant replied that he hadn’t seen any similar cases. Two weeks later, Conant contacted Friedman-Kien and said he had learned of similar cases at a dermatological conference; a case of KS at Stanford and another in the private practice of James Groundwater, MD. Friedman-Kien knew Groundwater and learned that he had seen six cases. He then contacted Curran to inform him of the KS epidemic in New York City and San Francisco. The CDC continued with investigations of Dugas and his sexual contacts in Los Angeles, Seattle, Boston and New York.

“What was interesting was the early patients with KS often didn’t have any other infections. They were healthy, except with the purple spots, which were very recognizable,” he said. “Being a virologist, I knew that this was the beginning of a terrible disease. I didn’t even know what the cause was, it was just the speed with which we were seeing cases that this was obvious that it was something larger.”

Second MMWR released

On July 4, 1981, the CDC released a second MMWR report, “Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men – New York City and California,” detailing the 26 cases of KS; 20 seen in New York and six in California.

“All these patients were dying of opportunistic infections and they were immunocompromised,” Friedman-Kien said. “Since it was essentially a disease only seen in gay men, it made me suspicious that this kind of cancer was not a true cancer but an opportunistic neoplasm.”

All 26 patients ranged in age from 26 to 51 years old. Eight patients died within 24 months of KS diagnosis. Six of the patients had pneumonia, four of which was confirmed PCP, one had necrotizing toxoplasmosis of the central nervous system, 12 were diagnosed with cytomegalovirus (CMV). Other symptoms included weight loss and fever.

The hospital’s cancer registry review showed no documented cases of KS in men younger than 50 at Bellevue Hospital from 1970 to 1979 and only three cases at New York University Hospital from 1961 to 1979.

“The occurrence of this number of KS cases during a 30-month period among young, homosexual men is considered highly unusual. No previous association between KS and sexual preference has been reported,” the researchers wrote in this MMWR. “Although it is not certain that the increase in KS and PC pneumonia is restricted to homosexual men, the vast majority of recent cases have been reported from this group. Physicians should be alert for Kaposi’s sarcoma, PC pneumonia, and other opportunistic infections associated with immunosuppression in homosexual men.”

Cases known

“After the first MMWR came out, the feedback from the medical community was immediate,” said Gottlieb, who is now in private practice in Los Angeles. “My phone started ringing immediately from all over the country with doctors who had similar cases. More and more cases were coming out of the woodwork. I can’t tell you how many stories I had heard from doctors who were training at that time in New York, Pittsburgh and San Francisco telling me that they had cases of AIDS six months before ours.”

Although both Gottlieb and Friedman-Kien’s MMWR reports mentioned immunosuppression as a common cause of opportunistic infections like PCP and KS, no one ever made any connection between the two.

“Unbeknownst to us, the CDC hadn’t told us that Dr. Gottlieb had seen six cases of PCP, which many of our patients had developed later on,” Friedman-Kien said. “We never drew a link between the two MMWRs because we didn’t know.”

The only commonalities researchers identified were that all the patients were young, gay men.

“We were desperately trying to find a causative factor, it was pretty obvious it had to be an infectious disease and a transmissible agent,” Friedman-Kien said. “Strangely enough Dr. Gottlieb did not see KS among those patients he had in LA.”

The CDC continued active surveillance throughout the nation, called upon state health departments to report cases and investigated unusual cases. Many patients experienced shortness of breath, pneumonia, weight loss, diarrheal disease, some had both skin manifestations and systemic manifestations of cancer and sometimes the cancer affected organs as well as the skin, according to Curran.

“We did a national case-controlled study of cases that occurred in gay men and found that the cases were predominantly from New York and California and tended to be in openly gay men in their mid-30s who had been sexually active for a long time,” he said.

Cases increase

Health officials realized early on that this disease was unique, an illness that caused the immune system to lose its ability to defend itself. More worrisome was the fact that whatever this was, it was spreading fast.

A number of theories developed about the possible cause of these opportunistic infections and cancers. Early theories centered on infection with CMV or STDs, the use of sexual stimulants such as amyl nitrite or butyl nitrate “poppers” and/or “immune overload.” However, future research found no etiological connection between what would become known as AIDS and “poppers,” according to Curran.

“Many of us on the task force at the CDC had worked closely in the gay community in studies of hepatitis B transmission and vaccine trials to prevent hepatitis B, so our leading hypothesis from day one was that an underlying virus could well be the cause of the epidemic,” he said. “We thought it could have been an alteration of a current virus, an abnormal response to a current virus or a completely new virus. This was not uniformly seen as the likely hypothesis and there were lots of other hypotheses out there.”

There was so little known about the transmission of what seemed to be a new disease and so much more to learn. Concern arose about infection and whether this disease could be transmitted by people who had no apparent signs or symptoms.

By December 1981, only a year into the investigation, an estimated 160 cases of opportunistic infections were diagnosed in the United States, most ending in death. By 1982, several CDC reports revealed similar opportunistic infections in not just gay men, but other populations, such as hemophiliacs, Haitians and intravenous drug users.

“When the first cases of pneumocystis pneumonia were reported to the CDC, they were reported in gay men. Shortly thereafter, within the next few months, cases were reported in injection drug users,” Curran said.

Next Month: Disease spreads, investigation continues and a name is given to a nameless disease.

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. Kaposi’s sarcoma and Pneumocystis pneumonia among homosexual men – New York City and California. MMWR. 1981;30:305-308.
• CDC. Follow-up on Kaposi’s sarcoma and Pneumocystis pneumonia. MMWR. 1981;30:409-410.
• http://aidshistory.nih.gov