'To break the back of the epidemic'

What do you get when you enlist hundreds of scientists and community members around the world in an effort to develop a vaccine to combat the AIDS epidemic?

Dr. Judith Wasserheit says that you end up with a challenge not unlike "making an elephant dance."

Yet that's the venture the newly appointed director of the HIV Vaccine Trials Network (HVTN) has chosen to lead.

Wasserheit, also an investigator in the Clinical Research Division, faces some grim statistics. Forty million people around the world live with HIV/AIDS. The disease is the fifth leading cause of death among people age 25 to 44 in the United States. More than 20 percent of the population of some sub-Saharan African countries are infected.

Most experts - including those at the National Institutes of Health (NIH) who in 1999 launched the worldwide network that Wasserheit directs - agree that a vaccine may be the only hope to halt the global epidemic.

From hope to weapon

But moving from hope to preventive weapon won't be easy. It may be the biggest challenge of Wasserheit's career, which includes 20 years of clinical and epidemiologic research in this country and abroad, as well as leadership roles at federal and local agencies designed to prevent sexually transmitted diseases.

"We're dealing with a very smart virus," she said of HIV, the human immunodeficiency virus that causes AIDS. "Infected individuals are symptom-free for a long time, which gives the virus plenty of opportunity to move silently from one person to another in an explosive chain of transmission. HIV easily forms resistance to drugs. And the disease is spread by a behavior that's very hard to change. People enjoy sex but often can't even talk about it."

Only part of solution

Clever vaccine design to foil the virus is only part of the solution, Wasserheit said.

"I've got to galvanize the efforts of stellar teams of clinicians, epidemiologists, behavioral scientists and laboratory-based researchers," she said. "Then we need to ask, how do you take the finest science and move it into populations around the world to make a difference in people's lives?"

The HVTN, with its more than 25 sites on four continents, was designed to be such a vehicle. Dr. Larry Corey, head of the Hutch's Infectious Diseases program, serves as principal investigator of the effort, whose mission is to develop and test preventive vaccines.

Among the network's components is the Statistical and Data Management Center, located at the Hutch and directed by Dr. Steve Self in the Public Health Sciences Division. The Hutch, in conjunction with the University of Washington houses one of the network's clinical vaccine units, directed by Dr. Julie McElrath of the Clinical Research Division.

Corey has the highest praise for his new colleague.

"Judy is experienced in scientific policy, she has a great background in the field of sexually transmitted diseases and HIV, and she knows all the major players," he said. "She also has experience running very large organizations and is known as a creative problem solver and a terrific people manager.

"Need I say more? She really does walk on water."

Experience in monastery, Bangladesh

Wasserheit, a Harvard Medical School alumnus with a medical specialty in infectious diseases, relishes taking the helm of an international challenge. She once spent six weeks in a monastery to learn Bengali and then lived in Bangladesh for two years to carry out the first population-based study of sexually transmitted diseases in the Indian subcontinent.

Her skill at translating infectious disease research into broad public-health programs internationally will be an enormous asset in her new role: More than half of the participating HVTN sites are located in developing countries.

As HVTN director, Wasserheit, also a professor of medicine at UW, will lead, coordinate, administer and support the research activities of all of the network's U.S. and international sites.

Her ultimate goal, she says, "is to break the back of the AIDS epidemic around the world."

She assumed her new role last September after almost 10 years as director of the Division of Sexually Transmitted Disease Prevention at the Centers for Disease Control, a $170 million effort with more than 700 staff. Prior to that, she helped to establish and led the sexually transmitted diseases branch of the National Institute of Allergy and Infectious Diseases at the NIH, after several years on the faculty of the Johns Hopkins University School of Medicine.

Unlikely prevention tool

Vaccines are not the only AIDS prevention tools. But Wasserheit said recent evidence shows that behavioral-based efforts alone are unlikely to effect the necessary change.

"Having worked in the field for two decades, it's become increasingly clear that we can't do it without a vaccine," she said.

"Getting people to talk about sexually transmitted diseases, much less asking people to change sexual behaviors, is very difficult. You can't deal with it if you can't talk about it.

"And since more effective drugs and drug combinations have been developed, there's a changing perception of risk that, in some populations, has led to a recent increase in HIV risk behaviors and cases of sexually transmitted diseases. That's not to say we won't need behavioral prevention strategies as well. But alone, those won't allow us to end the pandemic."

Unique challenges

Both the laboratory scientists who develop HIV vaccines and the epidemiologists, physicians and statisticians whose job is to evaluate and implement vaccines face a number of challenges unique to the disease.

HIV undergoes rapid mutation during the course of infection, which leads to production of variant viruses with distinct immunological properties such that each stimulates a unique infection-fighting response from the body.

That's part of the reason why the body can't successfully eliminate the infection on its own. It's also why vaccine design has proved so difficult. Immunization against one form of the virus may have little or no benefit against other forms.

Wasserheit said that the first vaccines won't be magic bullets, nor are they likely to be the same vaccines used 50 years from now.

"The first generation of vaccines probably will offer only partial protection and work primarily by decreasing infectivity," she said. "But even partial protection, combined with other modalities, could help tip the scales and reverse the epidemic spread in some parts of the world."

Deciding whom to vaccinate, and at what age, is the subject of vigorous debate, Wasserheit said.

"For many diseases we're familiar with - measles and polio, for example - we've implemented vaccines in childhood," she said.

Infection in young adulthood

"But HIV infection typically occurs later, in young adulthood. Do we single out those likely to be at highest risk? How do we reach those individuals? What behavioral and other interventions need to go along with the vaccine strategy?"

The network is testing vaccines in Phase I and Phase II clinical trials, and hopes to begin at least one large-scale Phase III trial by early 2003.

"That trial would involve thousands of people," Wasserheit said. "It would be a quantum leap for us in terms of science and network capacity."

Her eagerness to tackle such a global public health issue stems as much from a social conscience as a passion for research.

"When more than a third of a population is infected, as it is in Botswana, that's mind-boggling," she said. "As I think about the public health challenges of our time, HIV infection and other sexually transmitted diseases, cancer, heart disease and mental health are the big ones."

All the more reason for an institution like the Hutch to support HIV research, she said. "We have an opportunity to have this truly stellar institution broaden its leadership to address another of the real public-health imperatives. If we can make major inroads in these areas in the next decade, we will have done something important."