The Body Covers: The 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV
Twelve Weeks of Atazanavir Treatment Reverses Nelfinavir-Associated Hyperlipidemia: Results From BMS AI424-044
September 24, 2002
In this study, patients who were taking stavudine (d4T, Zerit), lamivudine (3TC, Epivir) and nelfinavir (NFV, Viracept) stopped their nelfinavir and switched it to atazanavir, 400 mg a day (two tablets a day). The parental trial (BMS AI424-008) was the phase II trial that lead Bristol-Myers Squibb (BMS) to select the dose of 400 mg once a day as the preferred dose of atazanavir. During that study, patients on the nelfinavir arm increased their cholesterol levels by 24 percent vs. 5 percent in the atazanavir arms and their triglycerides went up 49 percent vs. 7 percent in the atazanavir arms.
After completion of the first trial, 63 patients switched from nelfinavir to atazanavir. Most of them had undetectable viral loads and their CD4 cell counts were well over 500. Most patients (except two) tolerated the switch well, though many of them developed hyperbilirubinemia, the most typical side effect of atazanavir. Total cholesterol went down from 213 mg/dL to 175 mg/dL after 12 weeks. LDL cholesterol decreased from 138 mg/dL to 104 mg/dL after 12 weeks. HDL cholesterol did not change after the switch. Triglycerides decreased from 156 mg/dL to 109 mg/dL. All of these changes could theoretically decrease the coronary risk of the patients taking these medications.
These findings are important and seem to confirm that atazanavir is associated with less lipid toxicity than other protease inhibitors. The main problem with this study was the lack of a control arm and the relatively short follow up (only 12 weeks). These findings need to be confirmed in a larger randomized trial. I am sure that BMS is planning that study. It looks clear to me that they'd like to position atazanavir as the first protease inhibitor. Obviously, potency is another important factor in making that decision. During ICAAC, the 24-week data of the large phase III pivotal trial of atazanavir will be presented. We will have to review that data and compare the potency of atazanavir to other protease inhibitors (though it's best to be careful about that, as comparing across protocols is always a risky business).
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