Drug works in treatment-naive, experienced patients
ABT-378 may help thwart resistant HIV
Clinicians searching for new treatments for patients who have drug-resistant HIV may look ahead to ABT-378, a drug now in phase III clinical trials.
The new drug, made by Abbott Laboratories in Abbott Park, IL, works with ritonavir in suppressing HIV RNA to fewer than 400 copies/ mL in 95% of treatment-naive patients and in 78% of protease inhibitor-experienced patients at 36 weeks.
Researchers took the ritonavir molecule and modified it to make it work against resistant HIV isolates. The result is a distinct compound that will have its own generic name, and it’s very different from ritonavir, says Joseph Eron, MD, co-director of the AIDS Clinical Research in the Infectious Disease Division of the University of North Carolina in Chapel Hill. Eron was involved in ABT-378’s phase II clinical research trials.
"They combine ABT-378 with a small amount of ritonavir to gain a big pharmacokinetic advantage," Eron adds.
The ABT-378/ritonavir combination proved to be very effective in a trial that included both treatment-naive and protease inhibitor-experienced patients. "We were able to show that two-thirds of the patients remain below detectable levels," Eron says.
ABT-378/ritonavir has a therapeutic index that averages equal to or greater than 30, which means it provides a barrier to viral resistance.1
Antiretroviral-naive patients were randomized to different blinded ABT-378/r groups receiving either ABT-378/r or d4T/3TC. Patients who had been treated with antiretroviral drugs previously were randomized to a blinded ABT-378/r group that also received nevirapine and two nucleoside reverse transcriptase inhibitors.
By the 36th week, 96% of the treatment-naive patients receiving ABT-378/r had fewer than 400 copies/mL, and 95% of the treatment-naive patients receiving d4T/3TC had fewer than 400 copies/mL. In both groups, 89% had achieved viral loads of fewer than 50 copies/mL.
ABT-378/r was well tolerated, with the most common side effects including diarrhea, nausea, asthenia, and headaches. There were two discontinuations for adverse events through the 36 weeks.
Abbott is working to put a 400/100 mg dose of ABT-378/ritonavir combination into one pill so patients don’t have to take drugs from different bottles, Eron says. "Some investigators are looking at ABT-378 as a once-a-day drug, but right now Abbott is taking a conservative approach of evaluating it as a twice-a-day drug."
Reference
1. Eron J, King M, Xu Y, et al. ABT-378/ritonavir (ABT-378/r) suppresses HIV RNA to <400 copies/mL in 95% of treatment-naive patients and in 78% of PI-experienced patients at 36 weeks. Abstract presented at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco: Sept. 27, 1999.
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