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RANDOMIZED TRIAL OF BICTEGRAVIR OR DOLUTEGRAVIR WITH FTC/TAF FOR INITIAL HIV THERAPY
Paul E. Sax1, Edwin DeJesus2, Gordon Crofoot3, Douglas Ward4, Paul Benson5, Xuelian Wei6, Kirsten L. White6, Hal Martin6, Andrew Cheng6, Erin Quirk6
1Brigham and Women's Hosp, Boston, MA, USA,2Orlando Immunol Cntr, Orlando, FL, USA,3The Crofoot Rsr Cntr, Houston, TX, USA,4Dupont Circle Physicians Group, Washington, DC, USA,5Be Well Med Cntr, Berkley, MI, USA,6Gilead Scis, Inc, Foster City, CA, USA
Because of their potency and safety, integrase strand transfer inhibitors (INSTIs) are widely recommended initial HIV-1 treatments in most major treatment guidelines. Bictegravir (BIC, GS-9883) is a novel, unboosted, once-daily INSTI that demonstrated potent activity in a 10-day monotherapy study and has in vitro activity against most INSTI-resistant viruses.
Treatment naïve, HIV-infected adults were randomized 2:1 to receive blinded treatment once daily with BIC 75 mg or dolutegravir (DTG) 50 mg; both were given with open label emtricitabine 200 mg/tenofovir alafenamide 25 mg (FTC/TAF). Treatments were administered without regard for food for 48 weeks. The primary endpoint was the proportion with HIV RNA <50 copies/mL (c/mL) at Week (W) 24 using snapshot analysis. Noninferiority was assessed through 95% confidence intervals (CI) at W24 and W48. Safety (adverse events [AEs] and laboratory results through Week 48) was a secondary endpoint.
Of 98 patients enrolled, 65 were randomized to BIC+FTC/TAF and 33 to DTG+FTC/TAF. Most subjects were male, had asymptomatic HIV infection, with median HIV-1 RNA 4.4-4.5 log10; baseline characteristics were balanced between arms. Virologic success (HIV-1 RNA <50 c/mL) at W24 was 97% for the BIC arm and 94% for the DTG arm, and at W48 was 97% and 91%, respectively (Table). One subject in the DTG arm had HIV-1 RNA >50 c/mL at W48. No viral resistance was detected in the BIC+FTC/TAF arm. Mean CD4 count increases at W48 were 258 cells/µL in the BIC arm and 192 cells/µL in the DTG arm. There were no treatment-related serious adverse events and no deaths. The most commonly reported adverse events were diarrhea (12% in each arm) and nausea (8% BIC, 12% DTG). One subject in the BIC arm discontinued due to an adverse event of urticaria following the W24 visit. Median changes in estimated glomerular filtration by Cockcroft-Gault (GFRCG) at W48 were -7.0 mL/min for BIC and -11.3 mL/min for DTG, with no discontinuations due to renal adverse events.
Bictegravir+FTC/TAF and DTG+FTC/TAF both demonstrated high virologic response rates at W24 that were maintained at W48. No treatment-emergent resistance was detected in the BIC+FTC/TAF arm through W48. Both treatments were well tolerated, and no significant safety signal was detected in either arm. Estimated GFRCG changes were consistent with known inhibition of tubular creatinine transport by BIC and DTG. Further evaluation of BIC for the treatment of HIV infection is warranted.