Phase II study comparing F/TAF/bictegravir vs F/TAF/dolutegravir

Comment: See abstract below.

This phase II study presents non-inferior results and several bictegravir phase III trials in both naïve and switch patients are underway in Australia and abroad. It’s great to see a study comparing a new agent to DTG, essentially the gold standard integrase inhibitor at present. 

Bictegravir represents a potentially exciting addition to the integrase inhibitor family-  a once daily, un-boosted medication with a high genetic barrier to resistance. It shares the same limitations as dolutegravir in terms of interaction with polyvalent cations and metformin boosting.

If all goes well, it will be co-formulated with F/TAF as a single pill regimen. Given its’ high barrier to resistance and absence of ABC, such a regimen may become an ideal option when initiating HAART in the absence of a resistance genotype/HLA-B*5701 result (eg in acute HIV infection or resource limited settings) or in individuals with high cardiovascular risk.

41 RANDOMIZED TRIAL OF BICTEGRAVIR OR DOLUTEGRAVIR WITH FTC/TAF FOR INITIAL HIV THERAPY

Paul E. Sax et al

Background: 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.

Methods: Treatment naive, HIV-infected adults 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.

Results: Of 98 patients enrolled, 65 were randomized to BIC+FTC/TAF and 33 to DTG+FTC/TAF. 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. 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.

Conclusion: Bictegravir+FTC/TAF and DTG+FTC/TAF both demonstrated high virologic response rates at both W24 and 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 GFR changes were consistent with known inhibition of tubular creatinine transport by BIC and DTG.