While a medical student at Duke University in the early 1980s, Diane Havlir followed with interest the early discoveries about the new immunodeficiency disease known as AIDS. Her curiosity deepened with an elective rotation in infectious disease at the Centers for Disease Control. Still, nothing could have prepared her for the onslaught of AIDS patients that flooded San Francisco General Hospital while she was a resident there in the mid-1980s.

"It was devastating," recalls Havlir. "Every night, ten or more patients would come in with advanced AIDS, but we had very little to offer them at that time." Physicians who worked with infectious diseases were used to treating infections and having good outcomes, she says. Being able to do nothing while so many patients died was new and deeply disturbing.

That experience was the kernel from which the rest of Havlir's professional life grew. After her residency, she left San Francisco to work on AIDS research around the country and around the world. She returned to UCSF as chief of the Positive Health Program at the UCSF-affiliated San Francisco General Hospital. As such, she is one of the key researchers who have transformed AIDS from an automatic death sentence to a dangerous but manageable chronic disease.

In college, Havlir had set her sights on becoming an environmental lawyer. In time, she became disillusioned with her choice. Her plans changed permanently after a trip to Costa Rica, where she studied nutrition in the elderly and became hooked on medical research.

After medical school and her residencies, Havlir and her husband moved to Cleveland, where she did an infectious disease fellowship at Case Western Reserve University. By the time she returned to California to become the clinical director of antiviral research at UC San Diego, she had committed her career to improving the care of HIV patients.

There were two main foci in research at the time, she says: treating opportunistic infections and trying to attack the virus itself. Havlir pursued research on both fronts, but it was on the latter that she registered her greatest victory. In those days, researchers were frustrated that the available retroviral agents couldn't get viral levels low enough to prevent HIV from becoming drug resistant. Once the virus became resistant it would again multiply rapidly, allowing the disease to return.

Havlir and her colleagues started testing combinations of two different antiviral agents, which suppressed the virus much more than a single agent. In the mid-1990s, her group became one of the first to treat patients with a multidrug "cocktail" of antiretroviral agents that they called HAART (highly active antiretroviral therapy).

Sustaining suppression

"We were able to sustain viral suppression first over a month, then six months, then a year," Havlir says. "For the first time we were able to change from talking to patients about how to die with AIDS to how to live with AIDS. People went from being inpatients to being outpatients."

At UCSF, Havlir, a mother of four, has continued to work on making this therapy more effective and easier to follow. For instance, the therapy required the patients to take many different pills at different times, and this high "pill burden" led to non-compliance and a recurrence of sickness. Havlir's research has resulted in understanding how simple but potent treatment regimens succeed.

Havlir has also initiated research on the course of disease for patients who respond well to therapy and who wish to take a break from medications. The immune system does become less effective when the therapy is stopped, but it does not collapse as some doctors had feared. Indeed, Havlir and her colleagues are quantifying the immune response after pills are discontinued so that patients and physicians can make decisions on when to stop and start therapy based on solid information.

Another current research area involves using vaccines to lower the viral load in those who are already infected. Patients who stop therapy may be able to use vaccines to delay the time when they have to restart therapy. "We are working on many ways of simplifying treatment as much as possible and making it easier for patients," Havlir says.

Havlir spends a great deal of her time on international AIDS work. "We are working with resource-limited countries to help them find the best ways to treat HIV. She has spent time working on programs in Latin America, Africa and India. In Uganda she is working with patients who have both HIV and tuberculosis. The tuberculosis infection seems to accelerate the progression of AIDS, and she is now doing trials to see if it is possible to halt that progression. In addition, Havlir is helping to set up a global drug resistance monitoring network through the World Health Organization. "HIV evolves so quickly on its own, particularly under drug pressure, that we need to develop strategies to identify and contain drug resistance."