Study: Adding 4th Drug to AIDS Cocktail Doesn't Help

A four-drug cocktail is not any better for treating newly diagnosed HIV infection than the standard three-drug regimen, according to a study that followed 765 patients for three years.

The finding is welcome news to patient advocates, despite the lack of a step forward in treatment. Adding a fourth drug would have raised costs in an already overburdened system in which some states report waiting lists of uninsured patients who need help paying for their HIV drugs.

The annual cost per person for antiretroviral drug therapy in 2001 was about $11,000 a year, according to a previous study.

Murray Penner of the National Alliance of State and Territorial AIDS Directors estimated that adding more drugs to already complex regimens could cost health systems millions of dollars more.

"Keeping treatment regimens as simple as possible is also good news for people living with HIV/AIDS as adherence (taking drugs as prescribed) is better with easier and smaller regimens," Penner said.

Adding a drug to the cocktail also could increase side effects and the potential for dangerous drug interactions, said Jim Pickett of the AIDS Foundation of Chicago.

The new study clears up a lingering question posed by the conflicting results of prior studies. Some smaller studies had found a quicker effect at beating back the virus when more drugs were added to the cocktail, while others found no added benefit.

"Triple drug therapy has been the standard approach to treatment of HIV infection for a decade or so, but there's always been a question about whether we could do better with more drugs," said study co-author Dr. Dan Kuritzkes of Harvard's Brigham and Women's Hospital.

"This reaffirms the potency of the current standard of care," Kuritzkes said.

Researchers made the two drug cocktails equally easy for patients to take, delivering both in five pills taken daily. Patients and their doctors didn't know which cocktail they were getting.

The study will appear in Wednesday's Journal of the American Medical Association and was released Sunday to coincide with the opening of the 16th International AIDS Conference.

Researchers found that the four-drug cocktail, which added the HIV drug abacavir, had no advantage in reducing the amount of virus in patients' blood. Compared with standard therapy, it also did not increase levels of CD4 cells that fight infection.

"Over the entire course of the study, at no point did there seem to be an advantage of the four-drug regimen," Kuritzkes said.

Supported by grants from the National Institutes of Health, the research was conducted at more than 40 U.S. sites. Several pharmaceutical companies provided drugs. Some of the researchers, including Kuritzkes, reported financial ties with the makers of HIV drugs.

More than half the patients in the study were black or Hispanic and almost 20 percent were female.

"It was a pretty diverse population that reflects the epidemic today," Kuritzkes said.

Black patients who took the drugs as directed did as well as white patients, but blacks who did not adhere precisely to the drug routine returned to high virus levels quicker than whites who did not take the drugs as prescribed. The reason for the difference was not clear, Kuritzkes said.

The study appears in a special issue of JAMA devoted to HIV/AIDS. The issue includes another study conducted in Botswana that compared breast-feeding and formula feeding for infants of HIV-positive mothers. Fewer formula-fed infants became infected with HIV, but they risked death from diarrhea and pneumonia because of a lack of sanitary water for making the formula. Another study in the issue found favorable patient outcomes after a rapid expansion of free antiretroviral therapy programs in Zambia.