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Switch to Bictegravir/F/TAF Noninferior to Staying with DTG/ABC/3TC
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25th Conference on Retroviruses and Opportunistic Infections (CROI), March 4-7, 2018, Boston
Mark Mascolini
Switching to a single-tablet combination of the integrase inhibitor bictegravir plus emtricitabine and tenofovir alafenamide (B/F/TAF) proved noninferior to staying with dolutegravir plus abacavir/lamivudine (DTG/ABC/3TC) in a double-blind randomized phase 3 trial [1]. Bone changes were similar in the two groups, and kidney markers differed marginally.
Bictegravir, an experimental HIV integrase inhibitor coformulated with F/TAF, has proved effective in previous trials, often going head-to-head against the popular integrase inhibitor dolutegravir [2-4] but also looking good against two protease inhibitors--boosted darunavir or atazanavir. Virus resistant to bictegravir did not emerge in any of these trials.
A new phase 3 trial explored a switch to B/F/TAF from single-pill DTG/ABC/3TC or DTG plus ABC/3TC. Everyone had maintained a viral load below 50 copies for at least 3 months with a DTG regimen, no one had resistance to study drugs, and everyone had an estimated glomerular filtration rate (eGFR) at or above 50 mL/min. The primary endpoint of this double-blind trial was the proportion of participants with a viral load at or above 50 copies at week 48 in a snapshot analysis. The trial assessed noninferiority of the switch to bictegravir versus continued DTG with a 4% margin around the 95% confidence interval (CI).
A team of investigators in Europe, North America, and Australia randomized 282 people to make the switch to B/F/TAF and 281 to stick with DTG/ABC/3TC. Median age stood at 46 years and ranged from 20 to 71. Women accounted for 11% of participants and blacks for 22%. Median CD4 count stood at 732 in the B/F/TAF group and 661 in the DTG group. Both groups had a median eGFR of 101 mL/min.
In the primary efficacy analysis after 48 weeks, 1.1% switching to B/F/TAF and 0.4% staying with DTG/ABC/3TC had a viral load at or above 50 copies. The 0.7% difference and 95% CI of -1.0% to 2.8% (crossing 0 and within the 4% bounds) established the noninferiority of B/F/TAF to DTG/ABC/3TC. At the 48-week point, 93.6% in the B/F/TAF arm and 95.0% in the DTG arm had a viral load at or below 50 copies (P = 0.59). No resistance to any study drugs emerged during the trial.
The most frequent adverse events were upper respiratory tract infection (10% in each arm), diarrhea (9% with B/F/TAF, 5% with DTG), nasopharyngitis (7%, 8%), and headache (7% in each arm). Six people (2%) assigned to B/F/TAF and 2 (1%) assigned to DTG/ABC/3TC stopped treatment because of an adverse event. The DTG/ABC/3TC group had a significantly higher proportion with any drug-related adverse event (16% versus 8%, P = 0.01). Proportions with any grade 3 or 4 lab abnormality were 17% with B/F/TAF (driven by transient amylase elevations) and 11% with DTG/ABC/3TC.
Bone mineral density increased at similar low rates in the two treatment arms through 48 weeks, and most kidney markers changed at similar rates. But eGFR rose 1.0 mL/min with B/F/TAF and fell 1.8 mL/min with DTG/ABC/3TC (P < 0.001). Lipid measures differed little between the two study groups, except for a 5-mg/dL triglyceride drop with B/F/TAF versus a 3-mg/dL gain with DTG/ABC/3TC (P = 0.028).
The researchers proposed that B/F/TAF "offers an effective and safe alternative to DTG/ABC/3TC."
References
1. Molina JM, Ward D, Brar I, et al. Switch to bictegravir/F/TAF from DTG and ABC/3TC. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 22.
2. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3 non-inferiority trial. Lancet. 2017;390:2073-2082.
3. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017;390:2063-2072.
4. Sax PE, DeJesus E, Crofoot G, et al. Bictegravir versus dolutegravir, each with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection: a randomised, double-blind, phase 2 trial. Lancet HIV. 2017;4:e154-e160.
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