Three-Drug AIDS Cocktail Is Tops

A three-drug cocktail used by many HIV-infected people proved clearly superior to other combinations at treating new patients in the biggest head-to-head comparison of AIDS medications to date.

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 patients' 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 over 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 HIV drugs on the market and hundreds of possible combinations, the latest findings could simplify doctors' decisions.

"It confirms what physicians have suspected for a long time," said Jose M. Zuniga, president of the International Association of Physicians in AIDS Care. "It's important to question and re-examine from time to time what become established standards of care on the off chance we're wrong."

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 now one of the U.S. government's three preferred initial regimens, and according to Zuniga is the most prescribed AIDS drug combination in the country.

"I've had fantastic success with this," said Dr. Patricia C. 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 dramatically extended the lives of people with the AIDS virus, 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 — were reported in Thursday'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, versus 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 K. Robbins, an AIDS specialist at Harvard Medical School and Massachusetts General Hospital.

However, Dr. Paul R. Skolnik of Boston University School of Medicine wrote in an editorial that the best regimen for a patient may differ with his or her circumstances.

A second paper then 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 researchers specifically warned against starting new patients on drug combinations including didanosine, or Videx, and stavudine, or Zerit, because they are less potent and have more toxic effects.

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.

By Linda A. Johnson