Feb. 7, 2001 Feb. 5, 2001 -- A new protease inhibitor has been shown to be safe, tolerable and effective at holding off HIV in HIV-positive patients with only one dose a day, according to data presented today by a University of Southern California researcher at the Eighth Conference on Retroviruses and Opportunistic Infections.
The drug—known as BMS-232632—differs from previous protease inhibitors in part because those drugs have required patients to adhere to complex dosing schedules. Doctors commonly prescribe one of a variety of protease inhibitors, in partnership with drugs called nucleoside analogs, in a pharmaceutical battle plan to combat HIV.
"Our study showed that BMS-232632 is a potent protease inhibitor that is well tolerated and can be used safely in combination with other anti-HIV therapies," said Kathleen Squires, M.D., associate professor of medicine at the Keck School of Medicine of USC. "This new drug offers patients once-daily dosing, and the additional benefit of a low pill burden."
The drug remains active in the bloodstream for longer than other protease inhibitors, making it effective over a longer period and at a lower dose than other protease inhibitors. Squires was a principal investigator for the first and second phases of the study, which was conducted at more than two dozen sites in numerous countries on three continents. The double-blind randomized 48 week-long study examined the safety and effectiveness of BMS-232632 (paired with two other common anti-HIV drugs known as stavudine and didanosine) compared to a currently available protease inhibitor called nelfinavir (also paired with the same two anti-HIV drugs).
Data from 480 patients showed comparable effectiveness of BMS-232632, at doses five to 10 times lower than nelfinavir, Squires said. The drug was just as effective as nelfinavir in reducing the reproduction of the HIV virus and increasing the number of virus-fighting immune cells, called CD4 T-cells, in the body.
Interestingly, and potentially important for HIV-positive patients, the new drug appears to have no effect on cholesterol and triglycerides, Squires said. Today’s commonly used protease inhibitors are associated with increases in cholesterol and triglycerides, which are known to increase the risk of cardiovascular problems.
The study also showed the drug produced fewer side effects. About 17 percent of patients taking BMS-232632 in the study experienced diarrhea, for example, far fewer than the 55 percent of patients taking the other protease inhibitor. The most common side effect seen from taking BMS-232632 was hyperbilirubinemia, or too much bilirubin in the blood. Although the condition can lead to jaundice in its extreme, the cases found in the study were only detectable through lab tests and were easily managed through a small reduction in the dose.
"It remains to be seen whether BMS-232632 has the potential to avoid other long-term complications such as lipodystrophy," Squires added.
Lipodystrophy is a common problem linked to protease inhibitors in which a patient’s belly swells or a pad of fat may grow behind the neck, while the arms, legs and face become gaunt. Because the drug also has been shown to work against HIV strains that already have grown resistant to other protease inhibitors, researchers hope to pursue its potential as a back-up protease inhibitor when patients fail their current regimen.
That will become increasingly important over time as patients on highly active antiretroviral therapy, or HAART, see the virus become resistant to the drugs they are currently taking—requiring a switch to new drugs.
Squires conducted the research at the University of Alabama at Birmingham before moving to USC. Squires and other investigators will soon begin phase III clinical trials in a number of other studies, in cooperation with the drug’s maker, Bristol-Myers Squibb, to further test effectiveness. Squires will soon begin the phase III testing at USC on the effectiveness of a 400 mg dose of the drug.
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