Anaheim, CA -- Even as access to potent new drug treatments increases, the effort to control the spread of HIV will be swamped by a sea of resistant microbes unless current strategies change, say a team of researchers led by a UC San Francisco scientist.

The warning stems from a new mathematical model that projects the course of the epidemic in San Francisco. It is based on the dynamics of HIV transmission and different projected levels of safe-sex practice in the gay community.

New combinations of protease inhibitors now offer great hope to those with HIV, but the total number of people infected with virus that is resistant to this drug regimen will climb as use of the treatment increases, the model shows. And, as the treatment becomes more widespread, some clinicians and patients are likely to be less rigorous with treatment protocol, the researchers predict. Finally, as gay people come to believe that control of the disease is possible, high-risk sexual behavior among some may increase.

Taken together, these patterns lead to what epidemiologists call "amplified perversity" -- the tendency for harmful trends to stack up and increase the severity of the epidemic.

"The model helps us see that community clinics must adhere very closely to a strict clinical-trial-like paradigm, and that high-risk sexual behavior must not return," said Sally Blower, PhD, leader of the study and associate professor of microbiology, immunology and medicine at UCSF. "Otherwise, the promise of controlling AIDS will vanish."

Blower spoke at a press conference today ("Update on AIDS Vaccines and other Infectious Diseases") at the annual meeting of the American Association for the Advancement of Science in Anaheim. She will present a summary of her team's research Saturday, January 23, at a session on "Mathematics of Epidemics and Disease" (9 a.m., Marriott 1st Floor Orange City Ballroom, Salon 2).

Helping move the study of infectious diseases into the area of prediction, Blower and her colleagues have developed three models that project the course of the AIDS epidemic in the San Francisco Bay Area, tuberculosis in developing countries and genital herpes in the US.

"The study of infectious diseases has traditionally been the practice of recording what has happened," Blower said. "But we must and can turn epidemiology into a predictive science." Because drug-resistant bacteria or viruses behave differently than their drug-sensitive counterparts, she said, a strategy that curbs an epidemic of drug-sensitive microbes can actually generate an epidemic of drug-resistant strains.

Tuberculosis offers a sobering example. Some three million people worldwide die every year from the TB bacterium. The World Health Organization (WHO) seeks to rid the developing world of TB, Blower said, by treating drug-sensitive TB cases but not the more difficult drug-resistant ones. Her research team developed a model to anticipate the effect of this strategy.

"We found that as you eradicate the drug-sensitive TB, you move toward a very rapid increase in the number of drug-resistant cases." The result of this so-called "perverse" effect is a new, even more intractable epidemic, this time involving drug-resistant TB. If its seeks to wipe out the scourge of TB, the World Health Organization must change its strategy, Blower said, and immediately begin treating drug-resistant TB in addition to drug-sensitive cases.

"Otherwise, current control strategies could eventually result in a three-fold increase in the TB death rate, and TB may become an even greater killer than it is today," she said.

The good news from the modelers concerns the genital herpes epidemic in the U.S. About 22 percent of Americans are afflicted with these contagious genital lesions, with numbers well above 40 percent in some inner cities. Only about five percent of American seek treatment, but Blower and her colleagues found that unlike the problem with TB, the mutation rate and other traits of herpes allows an aggressive treatment program without generating a dangerous number of drug-resistant cases. In fact, they found, hundreds of cases of drug-sensitive genital herpes could be prevented for every case of drug-resistant strain that would be created by the treatment program.

The take-home message: "Each viral or bacterial epidemic will be different, depending on the biology of the organisms, the genetic mechanism by which drug resistance develops and the treatment regimens. The purpose of the models is to determine when treatment will be effective in controlling epidemics, and when it may cause more harm than good."

Members of the research team include Graham Darby, PhD, international director for viral diseases research at Glaxo Wellcome Research and Development; JL Gerberding, MD, associate professor of medicine at UCSF; Robert M. Grant, MD, UCSF assistant professor of medicine, director of the Gladstone/UCSF Laboratory of Clinical Virology and staff research scientist at the Gladstone Institute of Virology and Immunology; Philip C. Hopewell, MD, UCSF professor of medicine and chief of pulmonary medicine at San Francisco General Hospital; Tom Lietman, MD, assistant professor of opthalmology in the Proctor Foundation at UCSF; Travis Porco, PhD, research scientist in the AIDS office at the San Francisco Department of Public Health; Peter M. Small, MD, assistant professor of medicine at Stanford University Medical School; Chuck Daley, UCSF assistant professor of medicine at the UCSF-affiliated San Francisco General Hospital Medical Center; and Hayley Gershengorn and Katia Koelle, both research scientists in Blower's UCSF research group.