In a vacant apartment building in Hartford's Charter Oak neighborhood, within walking distance of Connecticut's state capitol and several of the world's largest insurance companies, anthropologist D. Scott Wilson, Ph.D., points the toe of his boot at a spent syringe. The last person to use it has bent the needle to prevent its re-use and the possibility of infection with HIV. “You see this a lot, which is a very good thing,” says Dr. Wilson, an AIDS prevention researcher working on a Yale-affiliated research project. Also strewn amid the glass and rubbish are small plastic bottles that once contained bleach or water and were part of needle-cleaning kits that Dr. Wilson and his colleague, outreach worker Maria Martinez, hand out on the streets.

They are one of two teams that roam abandoned buildings, crack houses and shooting galleries in Hartford, with the aim of learning the rules that govern behavior there. Ultimately they hope to persuade drug users to adapt those rules to include HIV prevention methods. Their work is one of four projects under the umbrella of Yale's Center for Interdisciplinary Research on AIDS, or CIRA. Established last September with a $10.8 million grant from the National Institute of Mental Health and the National Institute on Drug Abuse, CIRA is a four-year effort centered in the Department of Epidemiology and Public Health, an accredited school of public health. Its goal is to change risky behaviors and stem the spread of AIDS. Yale's CIRA joins centers at UCLA, Columbia University, the Medical College of Wisconsin and the University of California at San Francisco as the fifth federally funded AIDS prevention center in the country. While most of CIRA's research will take place in Connecticut, the center is expected to develop prevention strategies that can be applied throughout the country and world.

“There is still a potential for the epidemic to spread even more dramatically than it has already in some populations,” says CIRA Director Michael H. Merson, M.D. “In many ways the worst is still to come.”

The former head of the World Health Organization's Geneva-based Global Programme on AIDS, Dr. Merson became Yale's first dean of public health in 1995. Since his return to the United States, he has sounded a persistent warning that advances in the treatment of HIV, while a great step forward, carry with them the risk of complacency.

Around the world, an estimated 30.6 million people live with AIDS or HIV infection, most of whom probably have no idea they are infected. Since the epidemic began, 11.7 million people have died of AIDS, according to UNAIDS, the worldwide AIDS program of the United Nations. The bulk of the world's cases are in sub-Saharan Africa, where an estimated 20.8 million people have been infected. Every day, UNAIDS reports, 16,000 people become infected with HIV. More than 90 percent of those new infections occur in developing countries.

In Africa, the hardest-hit continent, AIDS travels predominantly through heterosexual contact. In Botswana last year, 43 percent of pregnant women tested in one urban center were HIV-positive. One in five adults in Zimbabwe are believed to be HIV-positive.

China, Asia's largest country, is facing two epidemics, one among drug users in the southwestern part of the country and another among heterosexuals along the coast where prostitution is re-emerging. In Thailand, there is evidence of a drop in new infections, thanks to prevention efforts that promote condom use, discourage visits to sex workers and offer young women opportunities other than commercial sex.

Although doctors have vastly better weapons to fight it, including new anti-viral treatments developed at Yale (See Hunting down HIV), AIDS remains a deadly disease. In the United States, 820,000 people were living with HIV or AIDS as of the end of 1997, according to UNAIDS. According to the organization's Report on the Global HIV/AIDS Epidemic, released in June at an international conference in Geneva, an estimated 410,000 people have died of AIDS in the United States. For most of the 1990s, acquired immune deficiency syndrome was the leading killer of people between 25 and 44. Now, with the first effective therapies in place, AIDS has dropped to second place, below accidents. But the path of the infection has shifted as well. “The epidemic in the United States had been confined historically to gay men. It's becoming more and more an epidemic of injecting drug users and their sex partners,” Dr. Merson says. The net effect, he says, will be more and more heterosexual transmission.

A focus on behavior

Avoiding AIDS is as simple, and complicated, as avoiding risky behaviors. In the United States, blood screening has virtually eliminated transfusions as a factor in the spread of HIV. Except among infants born to HIV-infected mothers–an increasingly rare occurrence in the United States due to the use of antiviral drugs by pregnant women–transmission has become a function of behavior, occurring through unprotected sex or needle sharing. Yet for those at most risk of contracting AIDS, preventing HIV infection often takes a back seat to daily survival–finding a place to sleep, getting a meal or procuring drugs.

CIRA's four initial projects are designed to help people who appear to be most vulnerable to HIV infection–the inner-city poor, adolescents and drug users. The anthropologists and outreach workers in Hartford hope to devise prevention measures for high-risk drug use sites. A team of psychologists is developing messages to change risky sexual behavior and evaluating which approaches are most likely to succeed. Another team is looking for ways to prevent both pregnancy and sexually transmitted disease in teenagers. The fourth team is studying needle exchange programs to determine whether their benefits, such as reduced risk of infection and increased access to treatment, travel beyond the immediate participants.

Ellen Stover, Ph.D., director of the division of mental disorders, behavioral research and AIDS at the NIMH in Bethesda, Md., says that CIRA stands out because of its focus on drug users and adolescents. “It's unique and it's where the direction of research is going,” she said. “In the AIDS area, we have always encouraged behavioral scientists to work with public health experts and infectious disease experts.”

Involving the community

The CIRA team includes psychologists, epidemiologists, anthropologists, lawyers, molecular virologists, ethicists, a management expert and physicians. “To really understand how we're going to prevent HIV, you have to look at it from various perspectives,” he says. CIRA has created a community advisory committee whose members include community leaders who also serve on an executive committee that advises the center on policy and research priorities. Dominick Maldonado, an AIDS education coordinator for the City of New Haven, is chairman of CIRA's community advisory committee. “In the past,” he says, “research was done and those of us in the community felt like guinea pigs.” This time things are different. Mr. Maldonado and Matthew F. Lopes, M.P.H. '77, a member of the Mayor's Task Force on AIDS and member of CIRA's executive committee, see a real effort to involve local groups. “We hope that we will come up with some interesting and novel ways of prevention that will be demonstrated to a wider population,” says Mr. Lopes, director of the AIDS division at the city health department, “not just in New Haven, but around the country.”

Statistics compiled by Connecticut's health department show increased rates of heterosexual infection and infection through intravenous drug use. Injecting drug users made up 51 percent of the 9,941 AIDS cases reported in Connecticut as of the end of May. That percentage is twice the national average. Men having sex with men constituted 24 percent of the cases and heterosexual intercourse was the mode of transmission in 15 percent, according to the state Department of Public Health.

Since 1990 white males have dropped from 48 percent to 38 percent of the state's AIDS cases among men. African Americans account for 38 percent of the AIDS cases in men, an increase from 35 percent reported in 1990. Of females with AIDS, 47 percent are African American, fewer than the 51 percent reported in 1990, but up from the 1994 rate of 44 percent. Hispanic women make up 25 percent of the state's women with AIDS.

“This is increasingly a disease of minority populations,” says Gerald H. Friedland, M.D., who directs the Yale AIDS Program, a treatment center for people with AIDS. He has been tracking the disease since the early 1980s, when as a physician at Montefiore Hospital in the Bronx, he was among the first to notice it among drug users. “The epidemic in New Haven and the entire Northeast has been an epidemic of vulnerable populations. That is increasingly the character of the epidemic nationally.”

As HIV spreads through a marginalized population, Dr. Merson finds a disturbing lack of political will to implement proven prevention strategies. Politicians won't support needle exchange programs for fear of being perceived as soft on drugs (See Politics 1; science 0). The teaching of safe sex in schools raises social and religious objections. All this, Dr. Merson notes, while television news anchors open their broadcasts with speculation about oral sex in the Oval Office. “Good public health policy is based on science. Unfortunately, when it comes to AIDS, science has too often been ignored,” he says, adding that AIDS never surfaced as an issue in the 1996 presidential campaign. “It was the leading cause of death in our young people and neither candidate wanted to talk about it.”

With those concerns in mind early in his tenure at Yale, Dr. Merson began discussing AIDS with colleagues in various disciplines. Yale had already been at the forefront of treatment programs with the Yale AIDS Program, and Yale researchers had conducted one of the first federally funded studies to evaluate the efficacy of needle exchange programs as an AIDS prevention measure, but Dr. Merson felt even more could be done. He found enthusiasm for an AIDS prevention project among his colleagues, but also some doubts that the federal government would fund another AIDS center. Dr. Merson persisted, got an encouraging response to his initial proposal from the NIMH, and submitted a plan. Last September Yale President Richard C. Levin announced the $10.8 million grant from the NIMH and NIDA. The funding will keep CIRA going for about four years, but those involved foresee a life beyond that. “Our vision for the center was that we would continue to have 15 to 20 domestic and international projects associated with it in one way or another, for a decade or more,” Dr. Merson said. “I would hope we could serve as an international resource in HIV prevention.” Among the projects envisioned are training in prevention research for scientists, developing research capabilities at community-based organizations and analyzing policies that relate to HIV prevention.

CIRA combines the efforts of more than 55 researchers from six Yale schools and departments as well as two Hartford-based partners, the Institute for Community Research and the Hispanic Health Council. Activities are centered around four major research projects and three “cores,” organizational units that support the work. One core handles administrative chores, another compiles the data collected and the third explores legal and ethical issues. Researchers are also working on 13 projects affiliated with CIRA, including studies of drug abuse among children and high-risk behavior of drug users infected with HIV.

Keeping everything organized falls to Caroline Roan, associate director of the center. She is in charge of setting up CIRA's infrastructure. “When I started, I was working on a laptop sitting on the floor,” she says. She relies on e-mail and telephones to keep people in touch, but also schedules regular committee meetings, brown bag lunches and evening seminars.

Sharing Ideas

The interdisciplinary nature of the project becomes apparent at an evening seminar in mid-February. As Peter Salovey, Ph.D., a psychologist who is co-director of CIRA and director of the project on framing persuasive messages, is explaining how to get the message out on risky sex, needles, condom use and HIV testing, Edward H. Kaplan, Ph.D., a management sciences expert who led the study of New Haven's needle exchange program, picks up a piece of chalk and begins to apply mathematical modeling to Dr. Salovey's theories. The topic is the not-always-logical thought process behind risky sexual behavior. Wearing a condom will produce a fairly certain result, says Dr. Kaplan. Not wearing a condom offers two possible results–getting infected or not getting infected. He charts the possibilities on a blackboard and begins writing formulas. “It could be perfectly rational for people not to use condoms if risk is perceived as small,” Dr. Kaplan concludes.

At a CIRA conference in late May, Alvin Novick, M.D., professor of biology and director of the center's law, policy and ethics core, leads a discussion on surveillance of AIDS cases and HIV infections. He poses a rhetorical question: Does the public health benefit of tracking cases of HIV infection outweigh individual rights to privacy?

Some states report only cases of AIDS, while others report cases of HIV infection. Fear of having their names on a list of those infected with HIV has made people reluctant to get tested for the virus. There are valid scientific reasons to compile such a list, Dr. Novick says, but equally compelling privacy issues. “You want to count people who are infected. They're all going to need health care. They're all potentially infectious to others,” he adds. “You could mandate the testing of everyone and then you'd have perfect surveillance. We would have to ask eventually whether it was the least invasive.”

At CIRA's first brown bag lunch in February, another ethical question surfaces. The topic is informed consent. How do researchers secure the cooperation of people they're studying, explain what they're doing and spell out their rights? “They have to know the purpose of what you are doing,” says Robert J. Levine, M.D., HS '63, professor of medicine and co-director of the law, policy and ethics core, who leads the discussion. “They have to understand the risks. They have to understand the benefits. They have to know the alternatives.” The discussion turns to another question. Can researchers guarantee confidentiality to drug users who have reason to fear the law? What obligations do they have to report illegal activities to authorities? “These are not the sorts of issues that have clear answers,” says Dr. Levine, chairman of the medical school's Human Investigation Committee. He and others note that CIRA is covered by a federal certificate that guarantees interview subjects confidentiality.

During an interview in her Hartford office, Margaret R. Weeks, Ph.D., associate director of the Institute for Community Research and director of CIRA's study of high-risk drug sites, says researchers are required to report child abuse. They will also act in life-threatening situations, such as overdosing. “Often it's a judgment call out in the field,” she says. Outreach workers will also make referrals for drug users who seek treatment and will offer health kits. “The benefits of understanding these places, in order to protect health for the public good, justifies our research. If we go in there to intervene, either to impose the law upon them or impose something else upon them, we undo our ability to do research.”

On the street

“Outreach workers. Kits and condoms,” shouts Dr. Wilson, one of the anthropologists studying drug sites, as he and Ms. Martinez climb the stairs of an abandoned building back in Hartford's Charter Oak neighborhood. Before leaving their office, they stuff their pockets and shoulder bags with condoms and kits that include small vials of bleach and water for cleaning needles. They also carry flashlights to help them find their way through abandoned buildings and avoid needles, feces and debris.

The condoms and bleaching kits serve two functions. They provide an opportunity for outreach workers to introduce themselves to drug users. But as an AIDS prevention tool, bleaching has a mixed record. It requires filling the syringe with bleach and holding the bleach inside for 30 seconds, then repeating the process three times. After bleaching, the needle should be rinsed with water. If done correctly, the procedure disinfects the needle and syringe, but some addicts don't hold the bleach inside for the required 30 seconds. Although they're not always used properly, Dr. Wilson believes there is a benefit to distributing the kits. “If anyone's using them at all,” he says, “it's better than no one using them.”

What researchers and, indeed, the entire CIRA project are up against becomes clear on Irving Street in Hartford's Upper Albany neighborhood. On a busy street corner between a police substation and a community health center the signs of drugs are all about. “Got a kit? Got a couple of rubbers?” two men ask as they approach anthropologist Stephen Cabral, Ph.D., and his colleague, outreach worker Glenn Scott. Both work at the Hispanic Health Council and are working on the high-risk drug sites project in Hartford. A moment later, a stocky man of medium height walks by. “I got what you need!” he says, assuming strangers have come to the neighborhood for only one thing. He doesn't miss a beat when he learns he has offered drugs to outreach workers. He smiles, shrugs his shoulders and turns down their offer of free condoms. He lingers to tell them that the last time he took them his girlfriend accused him of cheating. Meanwhile Mr. Scott talks with Jeffrey, a tall, skinny man on his way to a Chinese takeout restaurant. Jeffrey has been in and out of drug treatment programs and laments some of the losses in his life, particularly a once-fine wardrobe. “I know what I'm doing is wrong,” says Jeffrey. “I've got to find something to replace it with.”

Down a side street Dr. Cabral and Mr. Scott wait outside a garage. Inside are two men who a few minutes earlier approached them on the street to ask for bleaching kits. One of the men comes out, and, embarrassed, says he and the other man are only using the garage to relieve themselves. After they have gone, Dr. Cabral and Mr. Scott look around to find the floor littered with pastel-colored glassine envelopes that once contained heroin. Before leaving, Mr. Scott places a fresh bleaching kit on top of some broken furniture in the hope that someone will use it.

The kit remains as a symbol of CIRA's goal–evaluating and implementing prevention measures that will stop the spread of AIDS. “Hopefully,” says Dr. Merson, “we can make a real difference in the nation in how we deal with this disease.” YM