IAC: Simple HIV Regimen Appears Safe and Effective

TORONTO, Aug. 13 -- Once patients have controlled HIV with a standard drug cocktail, treatment with a "boosted" protease inhibitor may be all they need to keep the virus at bay, researchers said here today.

It's a novel idea that appears to work, but still needs large-scale confirmation in controlled trials, according to Susan Swindells, MBBS, of the University of Nebraska Medical Center in Omaha for the AIDS Clinical Trials Group 5201 Study Team.

The findings by Dr. Swindells and colleagues, presented at the 16^th International AIDS Conference, were published simultaneously online in the Journal of the American Medical Association and will appear in the Aug. 16 issue.

In a preliminary prospective open-label study, Dr. Swindells and colleagues enrolled 36 HIV-positive patients, all on a protease inhibitor-based regimen, who had suppressed their virus to fewer than 50 copies of viral RNA per milliliter of blood for at least 48 weeks.

The study excluded patients if they had prior resistance to protease inhibitors, had received non-nucleoside reverse transcriptase inhibitors, were positive for hepatitis B surface antigen, or had cardiac conduction system disease.

The patients switched from their prior protease inhibitor to Reyataz (atazanavir), boosted with Norvir (ritonavir) at the start of the study, and then stopped taking the nucleoside reverse transcriptase inhibitors in their regimen six weeks later, Dr. Swindells said.

The primary endpoint of the study was virologic failure -- rebound to 200 or more copies of viral RNA per milliliter of blood -- within 24 weeks of stopping the other medications, she said.

Data from 34 patients were analyzed, Dr. Swindells said, and only three patients suffered virologic failure, for a success rate of 91%.

Plasma Reyataz levels were low or undetectable in two of the three failures, she added, noting "this strongly suggests they didn't take their medications." They switched to other regimens, she said, and re-suppressed their virus.

The third patient who had virologic failure re-suppressed the virus without switching and remains on Reyataz, Dr. Swindells said, but was counted as a failure in the data analysis.

Resistance testing at failure did not find any mutations conferring resistance to protease inhibitors, the researchers found, none of the patients dropped out because adverse effects, and there were no significant changes in plasma lipid levels.

Also, Dr. Swindells added, "the CD4 counts really didn't do anything exciting." Before the study, while the patients were taking their full HAART regimen, the mean CD4 count was 616 cells per milliliter of blood. At baseline, when they dropped the two nucleoside reverse transcriptase inhibitors, the count was 588 on average, and at week 24, the study's endpoint, the count was 604.

The researchers chose Reyataz for study, Dr. Swindells said, because it is taken once daily, it is known to cause fewer lipid abnormalities than other protease inhibitors, and it has a unique resistance profile so that if resistance developed it would not rule out other treatment options.

Dr. Swindells noted that the study is preliminary and needs to be confirmed by a larger randomized study. But, she added, the researchers have now completed 48 weeks of follow-up and most patients appear to be doing well on the simplified regimen, although the data have not yet been analyzed.

Earlier attempts to reduce the number of drugs needed to control HIV were unsuccessful mainly because medications weren't powerful enough, commented Stefano Vella, M.D., director of Italy's national health agency, the equivalent of the National Institutes of Health.

"Maybe with new drugs we can diminish the number, but it's still experimental," said Dr. Vella, a former president of the International AIDS Society.

The study was funded by several NIH grants and by industry support from Bristol-Myers Squibb, maker of Reyataz, and Abbott Laboratories, maker of Norvir, in the form of supplying study drugs and participation on the protocol team.

Dr. Swindells reported receiving research grants or contracts from or was a consultant for Abbott Pharmaceuticals, Bristol-Myers Squibb, Novartis, and Pfizer.