Dean James Curran began studying AIDS 18 years ago.

by Rhonda Mullen hen the first cases of Pneumocystis pneumonia were reported to the Centers for Disease Control and Prevention in 1981, James Curran was assigned to a task force to study those cases. Curran, now dean of the Rollins School of Public Health, thought he'd work on the project for three months. He didn't realize it was the beginning of a new era. It was a time before AIDS had a name, two years before HIV was identified, four years before the vast extent of the epidemic would become clear: that hundreds of thousands of Americans were already infected with a progressive disease that would most likely kill them. In the past two decades, researchers have compiled an astounding body of knowledge about AIDS: That the disease is caused by a retrovirus, that it is transmitted through the blood, that it can be prevented. Yet, a cure remains elusive. What has become clear is that conquering this ever-changing disease will require the combined efforts of experts in basic, clinical, and behavioral sciences. Curran, some 18 years later, now finds himself as principal investigator of one of 17 Centers for AIDS Research (CFAR), officially designated by the National Institutes of Health (NIH). With a $2.3 million grant, the Emory/Atlanta CFAR is a collaboration among academic, public health, government, and private AIDS researchers and clinicians - more than 100 investigators in the Atlanta area. The schools of medicine, public health, and nursing as well as Yerkes Primate Research Center are all involved. Emory's other major partners include the AIDS Research Consortium of Atlanta (ARCA), a group of clinical researchers who developed an HIV/AIDS clinical investigative structure that has become a model for other programs around the country; the Ponce de Leon Center, which is a part of the Grady Health System; and one of Emory's major affiliates, the Atlanta Veterans Affairs Medical Center.

John Altman's colloborations with Harriet Robinson and other researchers represent the interactions now taking place at Emory in its search for an AIDS vaccine.

ccording to many of those who helped draft the successful application to NIH, the time was right for Emory to apply for the grant. Many experts, both Emory veterans and new recruits, had begun to assemble at the university. For example, a team of internationally renowned immunologists and virologists joined the faculty of the School of Medicine and Yerkes, including Rafi Ahmed, John Altman, Mark Feinberg, and Harriet Robinson--all stars in their fields and all pursuing the quest for a viable AIDS vaccine. At the same time,behavioral scientists at the Rollins School of Public Health (RSPH) were completing intervention studies with at-risk populations, including women and adolescents. In the clinical area, too, AIDS research was assuming a growing prominence at the university, with clinical trials taking place under Jeffrey Lenox, director of the Ponce Center, as well as David Stephens, director of the School of Medicine's division of infectious diseases, and David Rimland, director of the AIDS Research Center at the VA, to name a few. Carlos del Rio, former executive director of the National AIDS Council in Mexico, also joined the clinical effort at Emory, bringing an international focus to the CFAR. All told, Emory faculty received more than $17 million last year for AIDS research. One advantage to being the relatively new kid on the block was that Emory's AIDS effort had less baggage than those at other institutions well known for AIDS research, says Feinberg, associate director of the Emory/ Atlanta CFAR. Upon leaving NIH's Office of AIDS Research, he identified Emory as the place where a vibrant AIDS research program was taking shape. "Programs at the well-known AIDS research institutions are less flexible," he says. "In a sense, they are resting on their laurels because it is hard for them as big institutions to adapt quickly to the fast-paced progress in AIDS research. Emory's commitment and its relative newness to the field gives it a real edge." Emory's access to patients offers another advantage. The Ponce Center alone is one of the most comprehensive outpatient HIV treatment facilities in the country. Emory physicians care for some 4,000 adults and children in more than 53,000 visits a year. The Ponce Center also participates in about 20 clinical trials at any one time, and many patients benefit from new drugs as well as a family-centered approach to care. Only a few miles away at one of four national VA AIDS research centers, clinicians treat more than 600 patients with HIV/AIDS each year. Emory researchers there study the disease from many angles - from hospital-acquired infections in HIV-positive patients to the genetics of viral drug resistance. Emory virologist Raymond Schinazi and chemist Dennis Liotta are leading an Emory team in developing antiviral compounds such as FTC (a nucleoside analog similar to AZT) that appear to shut down the virus' ability to reproduce.

Emory has the biggest commitment to vaccine research outside of NIH and the most promising vaccine research program in the world, says associate CFAR director Mark Feinberg.

hile ongoing work to solve the mysteries of AIDS stretches across many more fronts, the typical academic mindset is to work in isolation. "This disease has so many interrelated aspects that we have to get together," says Feinberg. More than with other diseases, AIDS requires multifaceted approaches to arrive at prevention strategies and a cure. New antiretroviral drug therapies for AIDS offer an example of how a combined approach is essential. Although this class of drugs has proven effective against HIV for some people, the regimen for the therapy is very complicated, needing patient compliance and improved patient behavior - a job for health educators. Additionally, these therapies have serious implications for how clinicians treat patients, and they interest basic scientists who want to understand how resistance to therapy develops. The need for interdisciplinary collaboration became clear when CFAR program coordinator Kimberly Sessions began making the rounds to meet AIDS researchers across Atlanta. She found that many researchers didn't know about others' work. For example, clinicians at the Ponce Center were unaware of complementary work in primates taking place at Yerkes, and some Yerkes researchers were equally uninformed about research at the Ponce Center. Developing a communications conduit was essential. Local researchers wanted a forum for networking, as was demonstrated on a cold, rainy evening last January at the inaugural meeting of the Vaccine Dinner Club. When CFAR leaders decided to host a new group for area investigators interested in all types of vaccine research, they had no idea how popular the idea would be. The club quickly attracted 246 registered members from all over Atlanta and as far away as Athens. Organizers expected 40 people for Rafi Ahmed's lecture on immune memory. More than 170 showed up for what has now become a monthly opportunity to share knowledge, sponsored by CFAR, CDC, Emory Vaccine Center, and the University of Georgia. For researchers interested in HIV-specific topics, CFAR launched the CFAR Interest Group, which also meets monthly.

ohn Altman, who will share his findings with the dinner club later this year, sums up the reason he came to Emory in two words: vaccine center. He is impressed by the Woodruff Health Sciences Center's commitment to developing a top-notch HIV vaccine program. The center has allocated tremendous resources of time and money for building a vaccine center, scheduled to open adjacent to Yerkes this fall. Altman brings a key component to Emory's hopes for developing a vaccine: a way to more accurately measure T cells that are specific to a particular virus. While at Stanford, he developed a tetramer technique that takes about an hour, as compared with the previous technique, which was more time-consuming, expensive, and difficult to replicate, as well as unreliable. The tetramer technique has become the gold standard of T-cell assays and is particularly important to AIDS research. In a study by Altman, Ahmed, and others, researchers found that the response of certain T cells, which provide the front line of protection against invading viruses, is considerably larger and more targeted to specific viral antigens than previously believed. "This research should prove important for vaccine development because you want a vaccine to induce a good response, and this research allows us to see directly what a good response is," Ahmed says. Altman works closely with Harriet Robinson, an expert on DNA vaccines and director of CFAR's developmental science core. As the principal investigator of an interdisciplinary molecular virology and immunology program, she is investigating DNA and protein immunogens for SIV (simian immunodeficiency virus) and HIV vaccines. Researchers administer a potential DNA vaccine for SIV to rhesus macaques, who are later given a booster shot of vaccine and eventually infected with SIV. Then, using Altman's tetramer assay, researchers test for T-cell immunity. In the past, such a test might take a month. With the new assay, researchers can have the results in an afternoon. Altman's collaborations with Ahmed and Robinson are representative of the interactions that are starting to take place at Emory. This sharing among basic scientists is necessary, as are more interdisciplinary studies, says Feinberg. Feinberg is attempting to develop a vaccine for HIV by adapting vaccines already used in humans, such as those for measles or yellow fever. His laboratory genetically modifies these vaccines to create a recombinant virus that expresses HIV antigens. He is working on the principles of natural immunity that kick in when someone receives a vaccine containing live virus. Feinberg believes CFAR allows AIDS research at Emory to advance to the next level of excellence and that the vaccine-related component will particularly distinguish this CFAR. "This is the biggest commitment to vaccine research outside of NIH," he says, "and the most promising vaccine research program in the world."

Behavioral research is a key component in the fight to stop the spread of AIDS. Under the guidance of Emory public health researcher Claire Sterk (left and below) and Sandi Comer-Cooper (right), whom residents call "Mom," this safe house opened in June for HIV counseling and testing. Few women availed themselves of those services for the first few months. But soon the word began trickling out to the streets that the staff here were trustworthy.

here's promise as well in one of Atlanta's rougher inner-city areas, where Emory health educators have created a safe haven for women, offering counseling and testing for HIV, in addition to clothing and food to women and families who need help getting back on their feet. This Health Intervention Project (HIP) is just one example of the headway behavioral scientists at Emory are making against AIDS. Funded by NIH, HIP is a collaboration between the RSPH and Georgia State University's department of sociology. HIP's principal investigator, Claire Sterk, is expert at such studies. A well-funded researcher and CFAR executive committee member, she's internationally known for in-depth work on the behavior of prostitutes and women who use drugs and those populations' risks for HIV. In one landmark study, Project FAST (Female Atlanta Study), Sterk collected information from women who use drugs in 14 communities to form a profile of patterns of female drug users. She was one of the first researchers to show that HIV prevention and drug therapy approaches that worked for men were often ineffective for these women. Building on that work, HIP examines the behavior of African-American women at risk for HIV from their own drug use or that of others. Those who enroll in HIP take part in seven sessions that cover topics from conflict resolution to information about AIDS. The study tests the motivation of at-risk people to change behavior and hopefully demonstrate both short- and long-term impacts of the intervention. Sterk also is studying the impact of HIV on inner-city mothers and daughters. Through individual interviews, she and her colleagues are trying to learn as much as they can about the impact of HIV, drug use, and violence on women who negotiate complicated lives in the urban community. In a study that takes a different tack, Sterk is examining the role of pharmacists as health educators for injection drug users. "Pharmacies are an ideal place for HIV intervention," she says. "We're trying to determine to what extent pharmacists see themselves as health educators, what they're taught about HIV in school, and to sort out legal issues involved with pharmacists taking on this role." HIV prevention requires a strong commitment to behavioral research, an area where Emory excels. That's clearly evidenced by NIH's support of Sterk and a host of other RSPH researchers - Ralph DiClemente, Gina Wingood, Colleen DiIorio, Ron Braithwaite, and Kenneth Resnicow - who work on HIV intervention with specific populations such as adolescents, women, and prison inmates. Behavioral scientists also give clinical and basic science researchers access to populations and can supplement a clinical plan with a behavior modification plan. Only when the disciplines come together do researchers have a chance to control the spread of HIV. Recently, Sterk sat together with other CFAR committee members, reviewing a group of 30 applications for seed money for AIDS projects on campus. As the projects were presented, basic scientists learned about a proposal using Hip Hop music as part of the intervention. Behavioral scientists learned a thing or two about new laboratory techniques being developed in basic science labs. "This experience brought people together to learn about each other's work, and as we reviewed the applications, we began to appreciate what others were doing," Sterk says. "It was a good moment. We have the same goal, but we need to learn how to break down artificial walls that shouldn't be there."

Carlos del Rio counsels patients with HIV at the Ponce de Leon Center of the Grady Health System.

arlos del Rio knows about breaking down barriers. As head of AIDS prevention and research in Mexico, del Rio completed many important studies on the use and accessibility of HIV testing, the impact of migration on HIV risk, and the economic impact of AIDS medical care in Mexico. In these investigations and others, del Rio combined both biomedical and anthropological disciplines. Del Rio continues his multidisciplinary studies at Emory with a joint appointment in the schools of medicine and public health and as associate director for clinical services at the Ponce Center and Grady Hospital. "One of my goals is to help develop an outstanding clinical research enterprise at Grady," says del Rio. In an ongoing study with other Emory collaborators, he is looking at the psychosocial influences on anti-retroviral use, including the social stigma felt by those who must follow the frequent and complex dosages of AIDS cocktails. In other studies, he is examining the molecular epidemiology of Pneumocystis carinii and trying to determine if the availability of a rapid test for HIV will encourage Grady Urgent Care Center patients to be tested for HIV and return for results. He also is involved in the international aspects of HIV. "More than 95% of people with AIDS now live in developing countries," he says. "Emory has an opportunity to be a big player in the international AIDS arena." Acting on that conviction, del Rio applied for an NIH designation as an AIDS International Training and Research Program (AITRP). Awarded last fall, the Emory AITRP ultimately will strengthen international efforts to combat HIV by providing foreign scientists specialized training to deal with the epidemic. AITRP is building on Emory connections in Mexico, Vietnam, and the Republic of Georgia. The program, which is explained at www.sph.emory.edu/AITRP, is supported through NIH's Fogarty International Center to advance health through international scientific cooperation. Specifically, the grant allows a select group of Fogarty fellows from those countries to receive education and training in AIDS and HIV research at Emory. They will take courses on campus that lead to graduate degrees and postdoctoral research training. Also, Emory researchers will provide in-country training and mentoring to fellows in their native countries. The program, in turn, offers Emory students opportunities to participate in overseas health research in collaboration with Fogarty fellows. "Our intention is to avoid being a scientific cowboy," says del Rio. "We don't plan to go in then leave nothing behind. Rather, this work allows us to draw on the human capital and intellectual capabilities in other countries to apply them to local problems." The university has committed to the global effort as well. In January, it helped launch a collaboration in Cuernavaca at Mexico's National Institute for Public Health, funded by a grant from the university's Internationalization Fund. In recognition of international HIV contributions, the United Nations also designated Emory as an AIDS Collaborating Center with del Rio as director. This international component distinguishes the Emory/Atlanta CFAR from many other CFARs in the nation, says Sessions. Last June, for example, ethicists, scientists, health educators, economists, health policy analysts, and frontline health care providers from developing countries came to Emory to share their perspectives of ethics in scientific research. CFAR, in collaboration with the Elizabeth Glaser Pediatric AIDS Foundation, sponsored the event in which participants focused on issues that investigators are likely to face in designing ethical, scientifically rigorous, and practically feasible interventions to prevent HIV transmission in developing countries. For example, economists attending the conference deemed one strategy proposed by the clinicians as financially impossible. "We are thinking locally and acting globally," Sessions says.

essions believes Emory's designation as a CFAR brings with it both good news and bad news. "The good news is that NIH was impressed with our program so that now we exist as a CFAR. That is an honor in itself," she says. "The bad news is that the funding we received, like so many other research programs around the country today, is less than we asked for. This CFAR designation allows us to get our foot in the door."

From the Director  /  Letters Emory & Columbia/HCA Open New Doors Q & A with Columbia/HCA EHCA at a Glance  /  Map Emory's Newest Chessman Global Attack on AIDS Taking Stock Moving Forward  /  Noteworthy Drug trials. Who needs them? Reaching Out to Nicaragua

In many ways, that represents just where the Emory/Atlanta CFAR stands. Many researchers are now working together to make a dent in the AIDS epidemic. With much less funding than originally requested, these researchers will have to be creative about how to disperse support. Realistically, researchers admit that some of the core areas may receive less support than others. For example, the vigorous push to strengthen the basic sciences and to develop an AIDS vaccine remains a high priority. "But a lot of CFAR's work isn't so much about dollars," Mark Feinberg emphasizes. "It's about opening communications and creating good will." The goal of all of these groups--whether basic scientist, behavioral educator, or clinician--remains the same: together to conquer the AIDS epidemic and bring relief and hope to those afflicted with this disease worldwide. For more information about CFAR and its interest groups, see www.sph.emory.edu/CFAR.