Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Reuters NewMedia - Thursday December 16, 1999
Gene Emery

Efavirenz's manufacturer, DuPont Co unit DuPont Pharmaceuticals, paid for the study of 450 volunteers, which appears in Thursday's New England Journal of Medicine.

The research is part of an ongoing attempt to improve on the "AIDS cocktail" that has dramatically extended the lives of people suffering from HIV, the AIDS virus.

In the latest study, doctors found that when efavirenz -- sold under the brand name Sustiva -- was combined with the drugs AZT and lamivudine, the amount of AIDS virus in the blood dropped to undetectable levels in 70 percent of recipients.

For patients who got indinavir -- sold under the brand name Crixivan by Merck & Co Inc -- combined with AZT and lamivudine, the success rate was only 48 percent.

A third group got indinavir and efavirenz; it worked in about 53 percent of the volunteers.

Lamivudine, also known as 3TC, is marketed as Epivir by Glaxo Wellcome. AZT, whose chemical name is zidovudine, is sold under the brand name Retrovir by Glaxo.

Fewer Side Effects With Sustiva Combination

Not only was the Sustiva combination more effective, it produced fewer side effects. Twenty-seven percent of people who got Sustiva discontinued treatment because of nausea, vomiting, pain, fatigue, and other side effects. In contrast, 43 percent of the Crixivan recipients dropped out.

In an editorial in the Journal, Dr. Nathan Clumeck of Saint-Pierre University Hospital in Brussels, Belgium, cautioned that the logistics of the study required indinavir recipients to take twice as many capsules as they normally would need to. The more pills a patient has to take, the less likely he or she is to take them all.

Sustiva is a member of a class of drugs known as non-nucleoside reverse transcriptase inhibitors (NNRTIs), while indinavir is a protease inhibitor.

Most drug cocktails include a member of the first class of HIV drugs, the reverse transcriptase inhibitors. Adding protease inhibitors -- like Crixivan -- greatly adds to its power.

But the NNRTIs are competing with the protease inhibitors, which are blamed for many of the unpleasant side-effects of HIV drugs, such as nausea, and for changes in metabolism that can cause odd fat deposits and, perhaps, heart disease.

Millions of dollars ride on which drug is most popular in a combination and companies compete fiercely to show that their particular drug has even a slight advantage over another.

Efavirenz-Nelfinavir Combination Helps Children

Thursday's Journal also has a study, led by Dr. Stuart Starr of the Children's Hospital of Philadelphia, that found that a combination of two NNRTIs, efavirenz and nelfinavir, plus AZT or anther reverse transcriptase inhibitor, was an effective treatment for 57 HIV-infected children. "After 48 weeks, the virus was undetectable in more than half of the children," said Starr. The most common side effects were rash and diarrhea.

The researchers did not compare the efavirenz-nelfinavir treatment to another drug regimen. Nelfinavir is made by Agouron Pharmaceuticals, now owned by Warner-Lambert under the brand name Viracept.

Nearly 2,000 U.S. children are infected with HIV, according to the Centers for Disease Control and Prevention in Atlanta.

In both studies, the patients knew which medicines they were receiving, which can influence the results.
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