By Steve Sternberg

USA Today 7 February 2001

Chicago -- People with advanced AIDS who were started on anti-HIV drugs in 1996 have now begun to reach the limit of the drugs' effectiveness -- and they are running out of time, says research out Tuesday.

Doctors blame mounting drug resistance and longstanding damage to the patients' immune systems for the drugs' waning benefit. "At some centers we are beginning to see AIDS and AIDS-related complications," says Steven Deeks of the University of California-San Francisco.

These drug failures have not yet occurred in enough people to appear in national statistics, Deeks says, but that will eventually change unless new classes of drugs can be developed.

David Ho of the Aaron Diamond AIDS Research Center in New York says new drugs are on the way, but they may not arrive in time to save people who began therapy in 1996. He cited one drug in particular, TMC126, that appears "particularly potent," but it has not yet been tested in humans.

Current medicines, prescribed in multidrug cocktails known as Highly Active Anti-Retroviral Therapy (HAART), cripple HIV, the AIDS virus, so that it can no longer replicate. But HIV has proved to be a wily adversary that mutates quickly and becomes resistant to the most potent drug combinations.

In a study of 300 patients who began treatment in 1996 with advanced disease, one in five have developed AIDS again or died over the past five years, Deeks reported at the Eighth Annual Retrovirus Conference here.

Many initially experienced "miraculous" responses to therapy, he says.

Deeks blames mounting drug resistance for the failures. Three studies presented Tuesday from the USA, Switzerland and France indicate that about 10% of people in those countries are initially infected with drug-resistant viruses.

Some doctors now advocate testing patients for resistant HIV strains. "People who are newly infected with resistant viruses are more difficult to treat," says Susan Little of the University of California-San Diego, leader of the U.S. study.

In a separate study out Tuesday, Michael Saag of the University of Alabama-Birmingham found that the health of a person's immune system when he started HAART also affects survival.

Doctors measure the potency of a person's defenses by counting T-helper cells, white blood cells that govern the immune response. More than one third of 380 people who started HAART in 1996 with a T-cell count of less than 200 per cubic milliliter of blood died within four years, compared with about 7% of those with higher counts. Overall, 73 of the patients have died.