Research shows poppers’ use is connected with infection among MSM

Little is done to address problem

Early in the AIDS epidemic, public health officials thought that poppers, a popular party inhalant used by gay men, might be a cause of the disease. When AIDS was proven to be caused by an infectious agent, most people dismissed poppers as having no relevance to HIV.

Now, more than 20 years later, research continues to show a strong link between the use of poppers and HIV risk behaviors. The studies that ask separately about popper use consistently show that it falls just below alcohol and marijuana as a substance of choice among men who have sex with men (MSM).1

And some research has found that popper use is related to unprotected anal intercourse, both insertive and receptive, whereas other drugs are not.2

Also, some studies have shown that poppers are associated with HIV infection and increasing HIV rates and not just risk behavior. All of this suggests that more education and HIV interventions that discuss the use of poppers, as well as other drugs, are needed.

"When HIV was discovered, the scientific, research, clinical, and gay communities crossed poppers off their list to be concerned about," says Hank Wilson, founder of the Committee to Monitor Poppers/Survive AIDS of San Francisco.

"But if we let gay men know that poppers make them more susceptible to HIV infection, then I think we’d see a big shift and change in behavior," he says.

HIV investigators are more cautious in their assessment of the impact of popper use on HIV, but those who have done research into it acknowledge that the substance should not be ignored by the prevention and research communities.

"Several groups, ours included, in the early days of the epidemic found this association between people who were among the earliest to become HIV-infected and popper use," says Kenneth H. Mayer, MD, an infectious disease physician at Miriam Hospital and a professor of medicine and community health at Brown University in Providence, RI. Mayer also is a medical research director at Fenway Community Health in Boston.

"It’s still tricky to disentangle whether popper use is a marker for risky sexual activity or a marker for HIV infection," he says. "There are studies that suggest that people who use poppers during anal sex have increased susceptibility of becoming HIV infected — it’s a correlation, not a causality."

Poppers is a slang term for fluids that contain amyl, butyl, or isobutyl nitrate, and which are inhaled from small bottles that traditionally made a popping noise when opened. They are basal dilators that relax the sphincter muscles, making anal intercourse less painful. This, in turn, can lead to more trauma in the rectum, which could be a factor in HIV transmission, Wilson says.

Another theory is that poppers increase blood flow to the rectal area and that could make it easier for a person to become infected when exposed to HIV through anal intercourse, says Grant Colfax, MD, director of prevention studies in the HIV Research Section of the San Francisco Department of Public Health.

It’s also possible that poppers cause immunosuppression. "Animal studies have shown that there is some immunosuppression — the immune cells don’t function as well," Colfax says. "I don’t think you can make any conclusions about what may be happening in people, but it suggests there might be something else going on with poppers."

Lee S. F. Soderberg, PhD, has researched the impact of inhalant use and Kaposi’s sarcoma in HIV-infected populations. He studied tumor growth in mice exposed to inhaled isobutyl nitrate and found that exposure to the inhalant increased tumor incidence and tumor growth rate by nearly four fold.3 Soderberg is a professor in the department of microbiology & immunology at the University of Arkansas.

His research also concluded that after five daily exposures to inhaled isobutyl nitrate, the induction of specific T cell mediated cytotoxicity was inhibited by 36% and the tumoricidal activity of activated macrophages was inhibited by 86%.2

Soderberg’s investigations also found that nitrate inhalants compromise a variety of immune mechanisms and may play an active role in promoting HIV replication and the growth of Kaposi’s sarcoma cells.4

Even without evidence suggesting a connection between popper use and HIV seroconversion, there is ample data to support the conclusion that popper use is a major risk factor among at-risk MSM.

"The problem with poppers is that every time you look at sexual behavior in the Multicenter AIDS Cohort Study (MACS) cohort, you always see that popper use is associated with higher risk sex behavior and seroconverting to HIV, if a person was negative to begin with," says David Ostrow, MD, PhD, coordinator of the Behavioral Working Group within MACS, which is based in Chicago; Pittsburgh; Washington, DC; and Los Angeles.

"The seroconversion rate was much closer related to popper use than the amount of unsafe sex they were having, so popper use is not just facilitating anal sex, it’s maybe making the virus easier to get into you," Ostrow says. "But nobody wants to believe that — there’s tremendous denial in the gay community that something seen as a very innocuous substance that gives a lot of pleasure to some people should be banned."

Actually, popper use was banned nationally in 1991, and for a while, it was difficult to find the drug; but that has been reversed since the Internet became popular, Wilson explains. "Today, we have over four dozen web sites that sell poppers on the Internet.They call it video head cleaner, leather cleaner, and the biggest manufacturer sells 25,000 daily."

Wilson is irked especially by Internet ads for poppers, which make claims that they are as safe as aspirin and have nothing to do with the AIDS epidemic. Although poppers are permitted to be sold only as incense, cleaners, air fresheners, and the like, the ads discuss the use of poppers as a sexually enhancing compound and offer advice on what to do if popper use causes a headache or impotence. The answer on one web site is: "Open the window, and take a deep breath."

The poppers web sites also warn against the use of poppers with Viagra, although they fall short of mentioning deaths that have occurred from the commingling of the two drugs, which both cause a drop in blood pressure.

To combat misinformation distributed on-line about poppers, communities and public health departments should distribute literature that more accurately explain the dangers of popper use, Wilson says.

"The challenge to prevention workers is that if we can predict that people will be offered poppers, are we offering them information so they can make an informed choice?" Wilson says. "Do we arm people with refusal skills?"

However, few programs meet this challenge.

"The problem is the denial in the community and the lack of public health campaigns," Mayer says. "It’s something AIDS service organizations are not paying much attention to."

For instance, while there currently is a big focus on crystal methamphetamine, there hasn’t been a focus on poppers in the gay community for years, Mayer notes.

Also, researchers correctly point out that some drugs that are used by fewer people than use poppers can cause a great deal of physical damage that is in addition to HIV infection, and then there are substances such as alcohol that are used by such a large percentage of at-risk people, that it should be a top priority in any intervention program.

Unfortunately, there are no proven HIV interventions that address popper use or the use of any other substances, says Ron Stall, PhD, chief of the Prevention Research Branch of the Centers for Disease Control and Prevention (CDC).

The National Institutes of Health has funded two completed studies, which have not demonstrated their interventions’ effectiveness, and now the CDC has plans to begin a third study, called Project Mix, this fall, he adds. "There is strong evidence that substance use is intimately connected among seroconversion of MSM, and that’s why the CDC is funding a new trial."

Project Mix is designed to help men examine the effects of substance use in their sexual decision making, Stall says. If the trial succeeds, its intervention strategy will be made available to community-based organizations as a tool to disentangle substance use and HIV infection, he explains.

As far as addressing popper use specifically, Stall says the spectrum of substance use among at-risk MSM is the real problem — not any one substance. "There are numerous studies now looking at substance use among MSM, and it’s very clear that MSM have higher rates of drug use than are found in the general population of men in America. However, very little of this use appears to be intravenous drug use; almost all are nonintravenous drugs, and particular drugs are popular among MSM, including poppers."

Another cluster of popular drugs used by MSM are cocaine, methamphetamine, and the so-called "party drugs."

"Another profile that’s very striking is that very few gay men use only one substance," Stall says. "So because of the many different drugs used in the gay community and because of multidrug-use patterns, it would be hard to say you could attribute HIV seroconversion to any one drug."

This multidrug-use pattern is one reason why some researchers have given up the specific study of poppers and HIV, researchers say.

"Nowadays, we don’t even separate poppers when we look at the [MACS] data," Ostrow says. "Our current investigations aren’t trying to gain further understanding of poppers — once you’ve done it 10 times, nobody wants to hear about it any more, so now the focus is on party drugs like Ecstasy."

References

1. Stall R, Paul JP, Greenwood G, et al. Alcohol use, drug use and alcohol-related problems among men who have sex with men: The Urban Men’s Health Study. Addiction 2001; 96:1,589-1,601.

2. Purcell DW, Parsons JT, Halkitis PN, et al. Substance use and sexual transmission risk behavior of HIV-positive men who have sex with men. J Subs Abuse 2001; 13:185-200.

3. Soderbergh LSF. Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters 1999; 104:35-51.

4. Soderbergh LSF. Immunomodulation by nitrate inhalants may predispose abusers to aids and Kaposi’s sarcoma. J Neuroimmunology 1998; 83:157-161.