SEATTLE — The investigational integrase inhibitor bictegravir worked as well as dolutegravir (Tivicay) and caused no serious side effects when used as part of a three-drug antiretroviral therapy regimen, a researcher said here. Bictegravir is now being evaluated in phase III studies.
Viral suppression rates were high in both treatment arms and no one taking bictegravir discontinued treatment early due to adverse events, according to Paul Sax, MD, of Brigham and Women’s Hospital in Boston.
“Results were outstanding for both treatment arms [and] both regimens were extremely well tolerated,” Sax told reporters at the annual Conference on Retroviruses and Opportunistic Infections (CROI).
Integrase inhibitors are increasingly important as part of initial HIV therapy, and this drug class is widely recommended for first-line treatment in most major antiretroviral therapy guidelines.
“We definitely have a much more extensive armamentarium of treatments for HIV, but there’s still some room for improvement,” Judith Currier, MD, of the University of California Los Angeles told MedPage Today. “New data about a new integrase inhibitor and about two-drug combinations will help give us more options for ensuring that all people with HIV are able to be effectively treated.”
Gilead Science’s bictegravir is a novel integrase inhibitor that is taken once daily without a “booster” drug. It demonstrated potent activity against both wild type and integrase-resistant viruses in a previous phase I study, according to Sax.
Sax and colleagues conducted a phase II placebo-controlled trial comparing bictegravir against dolutegravir for first-line HIV therapy, both in combination with tenofovir alafenamide and emtricitabine.
This double-blind study included 98 treatment-naive adults. Most were men and they generally had asymptomatic HIV infection with a median viral load of approximately 4.5 log copies of HIV RNA per mL at the start of the study.
The investigators randomly assigned participants on a 2-to-1 basis to receive 75 mg bictegravir or 50 mg dolutegravir, each with a matching placebo of the other drug. These were taken with 25 mg tenofovir alafenamide and 200 mg emtricitabine once daily, with or without food, for 48 weeks.
The study’s primary endpoint was the proportion of people with HIV RNA below 50 copies per mL at 24 weeks; Sax also reported results at 48 weeks.
Both treatments were highly effective, with 97% of participants in the bictegravir arm and 94% in the dolutegravir arm achieving viral suppression at 24 weeks. At 48 weeks the response rates were again 97% with bictegravir and 91% with dolutegravir. Sax noted that given the small number of patients, these differences were not statistically significant and this study was not powered to determine full non-inferiority.
Three participants met the study criteria for virologic failure and underwent viral sequencing for drug resistance. “No significant resistance was detected in any patients in either the bictegravir or the dolutegravir arm,” Sax told reporters.
Both treatment regimens were safe and well tolerated. There were no treatment-related serious adverse events or deaths. Diarrhea and nausea were the most commonly reported adverse events. Kidney function, as measured by the estimated glomerular filtration rate, declined by 7.0 mL/min in the bictegravir arm and by 11.3 mL/min in the dolutegravir arm; no patients stopped treatment due to renal adverse events. One patient in the bictegravir arm who had a previous history of allergic dermatitis stopped treatment after 24 weeks due to hives, according to Sax.
These results were promising enough to proceed with phase III trials, and four of these studies are now fully enrolled, Sax said. Two are similar to the current study but using a single-tablet regimen of bictegravir, tenofovir alafenamide, and emtricitabine instead of separate pills. Another study is comparing the bictegravir coformulation against an approved coformulation of dolutegravir, abacavir, and lamivudine (Triumeq).