Once-Daily TAF Regimen Safer Than Stribild

There's a safer new player in the pipeline of once-daily HIV regimens, and it is known as TAF. Researchers at Gilead Sciences have found that it's similar to the current frontrunner Stribild, but demonstrates a more favorable renal and bone safety profile.

"These results suggest that TAF has the potential to be an important advance for people living with HIV," said Paul Sax, MD, clinical director of the Division of Infectious Diseases at Brigham and Women's Hospital, Boston, Professor of Medicine at Harvard Medical School, and an investigator for Study 102. "In this study, the TAF-based regimen matched Stribild's high viral suppression and demonstrated a favorable safety profile with respect to renal and bone changes."

TAF is a once-daily single tablet HIV regimen containing tenofovir alafenamide fumarate (TAF), elvitegravir, cobicistat and emtricitabine. Gilead Sciences announced this month that the 48-week results of their Phase 2 study showed that the effects were similar to the newest single tablet HIV regimen Stribild, but with higher renal and bone safety.

TAF is a nucleotide reverse transcriptase inhibitor and has the potential to provide greater antiviral efficacy at a dose that is ten times lower than Viread. The TAF/elvitegravir/cobicistat/emtricitabine regimen is currently being evaluated in two Phase 3 studies.

Researchers discovered that at 48 weeks, a regimen of elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/TAF 10 mg was found to be similar to Stribild, based on the percentage of patients with HIV RNA levels less than 50 copies/mL. These findings were presented on Sept. 12 in a late breaking session at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2013) in Denver.

Both regimens were generally well tolerated, with no treatment-related serious adverse events. But there were numeric differences in laboratory abnormalities of renal and bone markers, which favored the TAF-based regimen. There was a statistically significant difference in the median change in estimated glomerular filtration rate (eGFR) from baseline to week 48, with eGFR decreasing by -5.5 mL/min in the TAF arm compared to a decline of -10.0 mL/min in the Stribild arm (p=0.041).

Additionally, there was a significantly smaller median percentage decrease in bone mineral density from baseline to week 48 for the TAF-based regimen compared to Stribild (-1.00 vs. -3.37 (p
"Based on these positive results, we believe that TAF has the potential to become a key component of next-generation single tablet regimens in HIV therapy," said Gilead's Executive Vice President, Research and Development and Chief Scientific Officer Norbert W. Bischofberger, PhD. "We are now completing enrollment of two Phase 3 clinical trials comparing a TAF-based regimen to Stribild in patients new to HIV treatment, and look forward to sharing initial results from these large-scale studies by the end of 2014."

For more information about the Gilead drugs Stribild and Viread, visit www.gilead.com. Additional information about the study can be found at www.clinicaltrials.gov.