Investigational Integrase Inhibitor Bictegravir Safe and Effective Against HIV in Early Study
A new integrase inhibitor known as bictegravir (BIC, GS-9883) was found to be well tolerated and effective as HIV treatment in a 10-day monotherapy study, warranting further investigation of the drug, according to research presented at ASM Microbe 2016 in Boston, Massachusetts.
The study was designed to evaluate the short-term potency of bictegravir compared with placebo at four different drug doses: 5 mg, 25 mg, 50 mg and 100 mg. Twenty participants were enrolled, with five participants in each arm -- four of which received the study drug and one of which received a placebo.
Individuals living with HIV were enrolled who had never been treated with an integrase inhibitor, had a baseline viral load between 10,000 and 400,000 copies/mL and had a CD4 count above 200 copies/mm3. Nineteen of the 20 participants were men and 13 were white; six volunteers were black.
After 10 days of once-daily treatment using bictegravir with no booster, all four study arms saw rapid declines in viral load that were sustained through the treatment period. Average viral load reductions were as follows:
- The 5-mg group saw a -1.45 log10 copies/mL reduction in viral load.
- The 25-mg group saw a -2.08 log10 copies/mL reduction in viral load.
- The 50-mg group saw a -2.06 log10 copies/mL reduction in viral load.
- The 100-mg group saw a -2.43 log10 copies/mL reduction in viral load.
There was a clear dose response relationship between dose and viral dynamics, noted lead study author Joel Gallant, M.D., M.P.H. When treatment was discontinued after day 10, viral rebound was delayed until day 14 for the 50-mg group and day 17 for the 100-mg group.
Three participants achieved viral loads below 50 copies/mL by the end of the treatment period (one in the 50-mg group and two in the 100-mg group).
In terms of safety, the drug was well tolerated. There were no serious adverse events or adverse events leading to discontinuation. The most common adverse events reported were headache in three participants and diarrhea in two participants.
Additionally, no resistance emerged after 10 days of treatment in any of the arms.
Going forward, Gallant stated that 75 mg would be the dose for bictegravir as a stand-alone drug. However, bictegravir is also currently being developed as part of a single-tablet regimen in combination with tenofovir alafenamide (TAF) and emtricitabine (FTC, Emtriva). As a coformulation, the bictegravir dose will be 50 mg because TAF and emtricitabine increase exposure to bictegravir, Gallant said.