Study: Three-drug combo works best for AIDS

By Linda A. Johnson
The Associated Press

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The combination works better and longer, is easier to take and suppresses the virus more quickly, the international study found, offering powerful confirmation of what many AIDS specialists already believed.

Among the study's other, more surprising findings: Four drugs are not necessarily better than three.

The study was also the first to determine the best sequence for drug combinations, critical information because medication must be changed when the virus mutates and begins to resist the first drugs.

Preliminary findings from the research were announced at an AIDS conference in the summer and have already changed the U.S. Department of Health and Human Services' guidelines for initial HIV treatment and doctors' prescribing habits.

With 20 drugs for the human immunodeficiency virus on the market and hundreds of possible combinations, the latest findings could simplify doctors' decisions.

The study involved patients at 58 hospitals and clinics in the United States and 23 in Italy. Researchers led by doctors at Harvard and Stanford universities tested several three- and four-drug combinations of six HIV medicines.

They found the best combination for people getting their first HIV medication was efavirenz, lamivudine and zidovudine, better known as AZT. The second two drugs are taken in a combination pill under the brand name Combivir, while efavirenz is sold as Sustiva.

The combination is one of the U.S. government's three preferred initial regimens, and according to Jose Zuniga, president of the International Association of Physicians in AIDS Care, it is the most-prescribed AIDS drug combination in the country.

"I've had fantastic success with this," said Dr. Patricia Kloser, a professor of public health at the University of Medicine and Dentistry of New Jersey in Newark who specializes in treating HIV-infected women. "Even when resistance shows, people are hesitant to go off it because it's so easy to take: one pill in the morning and two at night, end of story."

While drug cocktails have significantly extended the lives of people with the virus that causes acquired immune deficiency syndrome, some require taking up to 21 pills daily, at different times and under specific conditions, such as with food or water.

That makes it tough for patients — especially ones who have other health problems or are homeless — to stick with the treatment. Missing even 5 percent of pills can speed up drug resistance.

The findings — contained in two research papers — are reported in today's New England Journal of Medicine.

The testing began in 1998. Nearly 1,000 patients were followed an average of 28 months, during which six patients each on the three- and four-drug cocktails died.

One paper compared different three-drug cocktails in 620 patients.

A drug combination is deemed a failure when the level of virus in a patient's blood rises, the number of key immune cells called CD4 cells drops or the drugs cause toxic effects, including damage to the nervous system, liver, pancreas and gastrointestinal tract.

After about 11 months, a failure occurred in 10 percent of patients on zidovudine/lamivudine/efavirenz, vs. 30 percent to 40 percent of those on other three-drug regimens.

Another advantage of this regimen is that it enables doctors to preserve a powerful class of drugs called protease inhibitors for later use, said study co-chairman Dr. Gregory Robbins.

A second paper compared the patients on the various three-drug cocktails with 360 others getting four-drug combinations. To researchers' surprise, four drugs were no better than the zidovudine/lamivudine/efavirenz combination.

The National Institute of Allergy and Infectious Diseases funded the research. Many of the lead researchers have served as consultants to or have financial interests in companies making AIDS drugs.

Copyright © 2003 The Seattle Times Company