Teaming up against the AIDS epidemic

SARA EDWARD-CORBETT/YH

In the summer of 1981, Dr. Gerald Friedland began to observe patients--mainly intravenous drug users--coming into Montefiore Hospital in the Bronx with symptoms unlike anything he'd seen before. With more and more patients presenting "very bizarre and opportunistic infections" such as fungal forms of pneumonia, Friedland grew gravely concerned. "I began to think very early on that this was a new disease," he remembered. "And although I couldn't have predicted precisely what would happen, I did know that this was not going to go away, and that we were in for a major catastrophe."

That major catastrophe--now known as AIDS--currently afflicts 33.4 million people worldwide, according to statistics just released in conjunction with the Tues., Dec. 1 commemoration of World AIDS Day. "The epidemic is wildly out of control in most of the world," Friedland, who now directs the Yale AIDS Program, said. "But there have also been major, really stunning advances in HIV care and treatment. It's both very exciting and gratifying--and quite depressing."

As a major research university in the heart of an urban setting, Yale is home to both the advances and the challenges of AIDS treatment. It was in Yale Medical School laboratories that one of the most widely-prescribed AIDS medications--a drug named Zerit--was invented. But the streets of New Haven have been "hit brutally hard" by the AIDS epidemic, according to Friedland, and he and his colleagues have been working to bring the scientific advances in AIDS treatment to the local community.

A 'one in 10,000' breakthrough

Back in 1953, when pharmacologist Dr. William Prusoff came to Yale, the AIDS epidemic was still decades away. But as AIDS came onto the map as a major health crisis, Prusoff turned his attention to the new virus--and in 1985, Zerit's story began.

Prusoff and his late colleague, Tai-Shun Lin, started to realize that d4t, a compound they were developing, had powerful anti-AIDS properties. The compound--which is now marketed as Zerit--works as a reverse transcriptase inscriptor, incorporating itself into the viral DNA chains and preventing them from reproducing.

"Prusoff disclosed the invention to me in 1985," Robert Bickerton, who oversaw the development of Zerit from start to finish as the director of Yale's Office of Cooperative Research from 1982 to 1996, remembered. "Since Prusoff's research was partly funded by a Bristol-Myers grant, we were obliged to go to them first," he explained.

When Bickerton talked to Bristol-Myers about the drug, the company wasn't overly enthusiastic. Prusoff was very excited about the drug's potential, but "the likelihood of its succeeding was considered to be one in 10,000," Bickerton said. He managed to get Bristol-Myers to fund research for one year, and the drug's effectiveness soon became clear.

Bristol-Myers spent seven years--and many millions of dollars--running studies before getting FDA approval in 1994. Over the past four years, Zerit has become one of the most widely-used ingredients of the "drug cocktail" treatments for AIDS patients, surpassing even AZT in prescriptions. "It's a great satisfaction knowing something you developed is of use to society," Prusoff said. "It's a fantastic satisfaction."

"Zerit's a very significant drug and has been very useful for a lot of reasons," Dr. David Kaufman, an internist who treats over 300 HIV-positive patients at his practice in downtown Manhattan, said. "It's really easy to take--just one pill twice a day--and the side effects are

minimal. In addition, it takes much longer for patients to develop resistance to Zerit. The virus must mutate many, many times before Zerit stops working."

Zerit's success has been a major financial boon for both Bristol-Myers and Yale. For Bristol-Myers, the drug brought in $398 million in 1997 alone. For Yale, Zerit has transformed royalty income into the fastest growing segment of University revenue. In just two years, Yale's total royalty income has grown from $3 million to $32 million as a result of Zerit's success. Indeed, the collaboration has been incredibly beneficial for Bristol-Myers and Yale--and for the AIDS patients who have been treated with Zerit. But for the substantial number of AIDS patients who don't have access to advanced medical technology, breakthroughs like Zerit are largely meaningless.

Bridging the gap

This issue deeply concerns Dr. Peter Selwyn, associate director of the Yale AIDS program. "To me, the biggest challenge with the AIDS epidemic in this country is to bridge the gap between the increasingly complex, effective treatments and the patient population in need of them--which is increasingly marginalized, vulnerable, and not well served by the existing system," Selwyn said. "That's where a lot of the focus of our program has been."

Selwyn, along with Friedland, was recruited in 1992 to help coordinate, develop, and expand the Yale AIDS program. The two nationally renowned AIDS specialists have built up the program dramatically.

"In 1992, it was clear to the Med School and to Yale-New Haven hospital that there had to be a response to the growing AIDS crisis, particularly because New Haven was affected very severely," Selwyn remembered. "It was a clinical, research, and public health crisis that led to their decision to build up the program."

The Yale AIDS Program is completely distinct from the research programs that produced Zerit. And like Prusoff's scientific research, the Yale AIDS program receives virtually all of its funding from outside sources. "The special projects are all grant-funded, with the hospital and Med School providing a certain base of funding for clinical outreach," Selwyn explained. "That's the standard--if you want to develop programs, the way you do it is by getting outside grants."

The program's mission has been to develop and integrate AIDS care across the continuum, ranging from outreach programs to outpatient care to inpatient service to the Leeway Nursing Home. "Our work is geared toward the particular characteristics and needs of the New Haven population which we treat, which is people who are poor, with a high prevalence of drug use," Selwyn said. "Before we developed the program, there was no separate unit for AIDS patients at Yale-New Haven Hospital." The program also started an outpatient clinic in 1992, which now sees more than 800 patients. Both clinics have social workers who help patients find monetary assistance for treatment.

Special delivery

One of the Yale AIDS Program's major outreach operations is the Community Health Care Van (CHCV). Created in 1993 by Dr. Frederick Altice, an associate director of the Yale AIDS Program and director of CHCV, the van travels to New Haven's various needle exchange sites four days a week. At each stop, it provides free medical care, substance abuse treatment, HIV counseling, social work, and case management. For those diagnosed with HIV, the van makes Zerit and other medications available free of charge.

"We started the program because we recognized that there was a large group of drug users--about 85 percent--who weren't in treatment for substance abuse. The van was deployed to provide treatment and HIV testing for them," Altice explained. Drug users are estimated to account for 51 percent of Connecticut's AIDS cases. The van treats both drug users and non-drug users; 20 percent of their patients are homeless.

"It's not that these people don't want to get medical care or don't want to comply with treatment," Migdalia Lopez, a case manager for the CHCV, said. "It's that they can't. The CHCV brings that to them, and links them with agencies in the community." As a case manager, Lopez works directly with the patients, encouraging them to get tested for HIV and helping them to find shelter, jobs, and medical coverage. "This week, for example, a homeless woman came to the van. It was a domestic violence situation--she had to leave her home, and then she started prostituting and using drugs," Lopez recalled. "The first thing I did when she came in was to place her in a homeless shelter. Tomorrow, I'll meet with her, get her in a substance abuse program, and get her tested for HIV."

Having worked with CHCV for nearly five years, Lopez has seen a dramatic increase in the number of patients using the van. "By word of mouth, more and more people have gone into treatment and have gotten the care they need. Many more people are getting tested for HIV," she reported. She estimates that the van now sees over 50 patients a day.

To Altice, the van is a crucial example of the need for AIDS treatment to extend beyond the University's borders. "We recognize that Yale is an ivory tower which isn't always accessible," he said. "We want to link the patients to Yale or to other community resources, but we also provide care on their own turf. People here have spent a lot of time trying to overcome the town-gown split."

The effort has paid off. Selwyn, Altice, and Friedland all believe that, over the past six years, New Haven has become one of the leading cities for AIDS care."One of the advantages of being in a small city is that it's more possible to integrate and coordinate efforts," Selwyn said. Altice agreed. "New Haven has really handled the epidemic much, much better than many other communities. People from the University and the community have come together and worked as a team," he said.

The psychology of prevention

The newest addition to the team is the Center for Interdisciplinary Research on AIDS (CIRA), which received a four-year, $11 million grant in 1997. Directed by Dr. Michael Merson and Psychology Professor Peter Salovey, CIRA has a new focus: behavioral prevention of HIV infection, particularly in vulnerable populations.

CIRA's focus on prevention is crucial, according to many AIDS specialists. "The thing that's so extraordinary is that we have known for over a decade now what you need to do to avoid getting HIV," Friedland said. "But people haven't been able to effectively do what's necessary."

To attack this problem, CIRA is focusing on four main research projects all taking place in New Haven. Salovey's project deals with "message framing"--how HIV prevention messages can be made more persuasive. "How do you maximize the impact of information?" Salovey asked. "It turns out that it depends on the circumstances."

There are two distinct areas of AIDS prevention: practicing safe behaviors and getting tested for HIV. Salovey's hypothesis is that positively framed messages are more effective for encouraging safe behaviors ("If you use condoms, you'll protect yourself against AIDS and stay healthy"), but that negatively framed messages are better at encouraging early detection ("If you don't get tested, you won't be able to get the treatment you need").

The subjects in Salovey's study are 500 low-income New Haven women who have been randomly assigned to various treatment conditions of either positively or negatively-framed messages. "We're following them every three months to see how many of them are getting tested," he said.

CIRA's other studies are looking at HIV infection in teen mothers, HIV prevention in high drug-using sites, and the benefits of needle exchange programs."We already know that needle-exchange programs work," Salovey said. "Now, we want to know whether the benefits of needle-exchange programs diffuse to the larger community."

Looking toward the future

Nearly 20 years after AIDS was first recognized, Friedland's grim predictions have unfortunately proven true. "Although the actual details of AIDS are in some ways worse than we might have anticipated, they are not a shock to me," Friedland said.

That said, the development of drugs like Zerit to the growing medical outreach in cities like New Haven are making a difference. "Locally, there have been really great accomplishments," Friedland said. "The mortality rate for AIDS has dropped by more than 50 percent in New Haven and Connecticut, and rates of hospitalization have dropped dramatically. People are living longer, in a healthier state."

As AIDS enters its third decade, Yale's specialists hope to expand these positive developments. "Those of us who provide treatment are going to be working closely with our behavioral science colleagues at CIRA," Altice said. "Their research should be guiding us."

Meanwhile, Prusoff--now in his 45th year at Yale--is still working to develop medications to bring AIDS under control. "Right now, I'm in the very early stages of exploring two types of compounds," he said, cautioning, "Who knows? It may be a complete bust."

Yet all agree that AIDS will be around for a long time to come. Prusoff believes that the best-case scenario is that AIDS will become a chronic disease, controllable by medication. "Even that would be fantastic," he remarked.

Friedland agreed. "HIV and AIDS will be with us for the rest of human history," he predicted. "Each successive generation is going to have to deal with this as a disease that one can acquire by ubitiquous human behavior. Anything that can be done to keep AIDS on people's minds and hearts--such as World AIDS Day--is very important for community survival."

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