Promising AIDS Drugs Seen as Becoming Easier to Use

WASHINGTON — Leading AIDS researchers said Saturday that the powerful new drug combinations having a major impact on AIDS patients are still too complicated and cumbersome to take, and they predicted that an imminent second generation of drugs will greatly simplify the task.

Most of the current drug “cocktails,” which combine potent new protease inhibitors--the most powerful of the new AIDS drugs--with older AIDS medications must be taken on a precise schedule three times a day and cannot be taken within two hours of eating.

The process is so difficult that many patients have lapses, which can cause the drugs to work less efficiently and can result in the development of mutant strains of the AIDS virus that ultimately become resistant to the drugs.

“We need to have drugs that can be taken once or twice a day, don’t revolve around meals and don’t cause toxicities, like headaches--things that have to do with convenience and that have an impact on people’s lifestyles,” said AIDS specialist Dr. Robert T. Schooley.

Schooley spoke at a press conference during the Fourth Conference on Retroviruses and Opportunistic Infections, a major scientific forum on AIDS held here this week.

Researchers also disclosed the results of a pioneering attempt to cure AIDS in newborn twins that will help determine whether it is possible to eradicate an AIDS infection.

The twin brother and sister, who caught the AIDS virus from their mother, have been given drug cocktails since the age of 10 weeks. The twins are now 18 months old and so far the girl is free of the virus, but it has returned in the boy. Doctors, however, say it is too early to declare the girl cured.

Experts believe that it may be possible to rid the body of the AIDS-causing human immunodeficiency virus, rather than simply keeping it from flaring up. Research on the twins raises the question: “Can we eradicate the virus? We don’t know yet, but if we are going to try, we want to do it as soon as the infection occurs,” said Dr. Catherine Wilfert of Duke University.

The study of the twins is important because doctors believe that if AIDS can be cured, it will most likely happen with patients whose immune systems have not already been wracked by HIV.

The new generation of powerful AIDS drug combinations is expected to be the subject of a presentation today by Schooley, who has been studying two new experimental drugs in patients.

“I think right now this combination looks extremely good,” Schooley said in an interview. “It has many advantages over the currently available regimens. The drugs work just as well, and may be much easier for people to take.”

They include a protease inhibitor, GW-141, and a nucleoside analog, GW-1592, both manufactured by the pharmaceutical firm Glaxo Wellcome.

GW-1592 is in the same category of drugs as older treatments in the AIDS arsenal--AZT, DDC and DDI--but it attacks the virus at a different base of its genetic code than the others, he said.

“It’s the first drug that has been developed based on this member of the code,” he said. “It hits the virus at the same place as AZT--but it does it 30 times more vigorously.”

Researchers are now convinced that such potent cocktails are the best strategy for controlling AIDS. The mixtures employ several drugs, each tailored to disrupt the virus at different stages in its replication process.

Schooley said side effects from the drugs are minimal, and they can be given twice a day. Also, they are not dependent on meal schedules. “There are no problems with food,” Schooley said.

He stressed, however, that experience with the drugs has thus far been limited because of a shortage of GW-1592. Patients have only been able to take it for four weeks and then must stop. At that point, they are switched to other drug combinations. Schooley said a new manufacturing process “should fix this up” within the next month.

“Obviously, we need to do the studies longer than four weeks,” he said.