Kaposi's, Viruses, & Poppers

By Tom Bethell
Rethinking AIDS April 1995

Perhaps the most remarkable development of recent months has been the announcement of a probable new cause of Kaposi's sarcoma. At the outset, this was the hallmark AIDS disease-the "gay cancer" of the early 1980s. Now, researchers believe it is caused not by HIV but by another virus. Lawrence K. Altman's page-one New York Times report on the claimed discovery, by a husband and wife team at Columbia University, did not mention HIV at all.[1] Lisa Krieger began her article in the San Francisco Examiner: "New research suggests that Kaposi's sarcoma, a potentially deadly disease long thought to be caused by HIV, is instead caused by a type of sexually transmitted herpes virus that preys on people with AIDS."[2]

Yuang Chang and Patrick S. Moore of Columbia used a new technique (representational difference analysis) to identify DNA fragments in Kaposi's tissue. These resemble Herpes sequences, but actual virus has not yet been isolated or cultured. What is suggestive is that the sequences have been found both in AIDS-related Kaposi's, and in the traditional, more benign form afflicting elderly men.

Four days after his first story, Dr. Altman wrote a second, asking (but not answering) a number of questions about the relationship between this new agent and HIV. [3] I asked Harold Jaffe, chief of AIDS research at CDC, some of these same questions, and some that were new.

"If this new agent is assumed to be the cause of Kaposi's, what role if any does HIV play in the development of KS?"

"Well, the answer is we don't know," Jaffe replied. "But certainly the risk of KS is much higher in people with HIV-related immunosuppression; about 300 times higher. That would either suggest that HIV-infected people have a higher rate of co-infection with this other virus, or there is something specific to HIV that increases the risk of KS. It is certainly possible that HIV and the putative KS virus could be working in a synergistic way."

"How confident are you that this new agent is the cause of KS?"

Since the initial announcement, Dr. Jaffe said, new information, presented at a conference in Washington, "showed that the same viral sequences were detected in different forms of KS-not just HIV-associated but in classical KS, and in African KS. I think this leaves us with two possibilities. One is that this is simply an opportunistic infection that likes to grow in this kind of tissue; or it is the cause. At this point we can't say which of the two it is, but I think it is certainly a good candidate to be the cause."

"Lawrence Altman asked why the percentage of AIDS patients with KS has declined in the last ten years."

"We don't know. That's been one of the mysteries. One possibility is that, if there is another virus (and let's say it's transmitted sexually), it may be that gay men have changed their sexual practices and so the rate at which they have been exposed to this new virus has decreased as well."

"Does the CDC believe that nitrite inhalants play any role in KS?"

"I don't think we can exclude that possibility. When you look at the epidemiology, what you have to explain is why Kaposi's is so much more common among gay men than among other HIV-infected persons. With the finding of this new agent, the answer may be as simple as: This new viral infection is much more common in gay men. Another possibility is that there is something about the lifestyle of gay men that is putting them at increased risk; and nitrite-inhalant use is certainly one thing that separates gay men from other sexually active people. I don't think the evidence for nitrites being a co-factor is very strong, though."

"Does the CDC say anything about the health effects of nitrite inhalants?"

"We haven't studied them in any context other than AIDS. We studied them early in the epidemic, with a question whether they were actually the cause of AIDS. Which of course they weren't. We were left with the question: Could they explain something like Kaposi's sarcoma? I personally think that is not the explanation but I don't think we can rule it out."

Harry Haverkos, director of the office of AIDS at the National Institute on Drug Abuse, has long believed that AIDS-related Kaposi's was caused by nitrite inhalants, or "poppers." A muscle relaxant, they were originally prescribed for angina patients. The volatile liquid came in a mesh-covered ampoule that was broken, or popped, and the fumes inhaled. In early AIDS studies, it was found that almost all KS patients admitted using nitrites, which have been used as muscle relaxants to facilitate anal intercourse. "Rare Cancer Seen in 41 Homosexuals," was the headline over an Altman story in July, 1981--one of the first articles written about AIDS.[4] "Many" of these men said they had used drugs "such as amyl nitrite." None of the patients knew one another.

Poppers are mutagenic in the Ames test, and Kaposi's lesions are most common on the face, nose and chest, where inhaled vapors are most concentrated; studies with human volunteers showed impairment of the immune system after a few days. Their heavy use has been confined to homosexuals. This declined after the onset of AIDS, when their danger was suspected by homosexuals themselves. Point-of-sale warnings were displayed and the incidence of Kaposi's likewise declined. (The warnings have since been allowed to lapse.)

In 1994, Haverkos made headway with his nitrite-KS hypothesis. The NIH sponsored a two-day review conference in May; speakers included Bob Gallo, Harold Jaffe, and a number of investigators who had done nitrite studies. A long article by John Lauritsen was printed in the New York Native [5]; in November, SPIN published an article about Haverkos and his ideas. Then the (possible) new KS virus came along. Six weeks later, participants at Washington's retrovirus conference were openly referring to the new Kaposi's agent as "KSHV." It was at that point that I spoke to Haverkos. I asked him what he thought of the new "virus."

"Well, it looks quite interesting," he replied. "I've read the Science piece [6]. They are able to find DNA sequences which they think are consistent with a Herpes virus; actually, it is most consistent with a Herpes virus that occurs in camels; they can't seem to find it if you go further out in the tissue; they do find it in a couple of lymphoma patients." The next step was to see if they succeed in growing the virus. Meanwhile, Patrick Moore is "doing the right thing, he is being cautious. He is not saying he has got it."

Haverkos allowed that the nitrite theory had been dealt a setback-if only because researchers would not take it seriously "until they have sorted out this new factor." Which could take time-a couple of years or longer.

It has all happened before. In the mid-1980s, he recalled, he was about to embark on a study of nitrites with the military when, just at that moment, the Armed Forces Institute of Pathology on the campus of Walter Reed Hospital in Bethesda came forth with the theory that mycoplasmas were a co-factor for KS. It didn't survive scrutiny, but "by the time they sorted it out, the impetus to do the study I had proposed had withered away, and the people at the Institute who were interested in nitrites had been transferred somewhere else."

Haverkos said he hadn't retracted anything about nitrites, but he probably wouldn't be very aggressive on the topic either. "Other than to ask," he added as an afterthought, "if this is a sexually transmitted virus, How come more women aren't getting it?"*

References

1. L. Altman, New York Times, 16 Dec 1994

2. Krieger, S.F. Examiner, 16 Dec 1994

3. L. Altman, New York Times, 20 Dec 1994

4. L. Altman, New York Times, 3 July 1981

5. J Lauritsen, New York Native, 13 June 1994

6. Y Chang et al, Science, 16 Dec 1994