Bictegravir -- It's Coming: A Top HIV Clinical Development of 2017

Last year's antiretroviral darling was dolutegravir (Tivicay, DTG). Now, the limelight has shifted to its integrase sibling, bictegravir. Requiring no pharmacological boosting, boasting a high barrier to resistance, and in early 2018 available co-formulated with tenofovir alafenamide (TAF, Vemlidy) and emtricitabine (FTC, Emtriva), the buzz around this agent is understandable. Two major randomized, double-blind trials involving bictegravir as initial antiretroviral therapy were presented and published this past year.

The first of these compared the fixed-dose combination of bictegravir, TAF, and FTC to dolutegravir plus co-formulated TAF and FTC. At 48 weeks, a plasma HIV RNA less than 50 copies/mL was achieved in 286 (89%) of 320 participants in the bictegravir group and 302 (93%) of 325 in the dolutegravir group (difference -3.5%, 95.002% CI-7.9 to 1.0, P = .12), showing the non-inferiority of the bictegravir regimen to the dolutegravir regimen. Overall, the regimens were very well tolerated, with scant discontinuations due to drug-related adverse effects and no treatment-emergent drug resistance detected.

The second study was similarly designed, but the comparator to the fixed-dose combination of bictegravir, TAF, and FTC was the fixed-dose combination of dolutegravir, abacavir (ABC, Ziagen), and lamivudine (3TC, Epivir). Once again, at week 48 both regimens did great with viral suppression below 50 copies/mL achieved in 92.4% of patients (n=290 of 314) in the bictegravir group and 93.0% of patients (n=293 of 315) in the dolutegravir group (difference -0.6%, 95.002% CI -4.8 to 3.6; P = .78), demonstrating the non-inferiority of the bictegravir regimen to this dolutegravir regimen. As in the other trial, no treatment-emergent resistance was detected. In this study, more nausea was experienced by those in the dolutegravir group (23%) compared with the bictegravir group (10%), likely due to the abacavir, as this was not seen in the other trial pairing the integrase inhibitors with TAF/FTC.

Related: Bictegravir vs. Dolutegravir

The Bottom Line

A testament to the relative advantages of integrase inhibitors is the recent update to the U.S. Department of Health and Human Services (DHHS) guidelines for the initial treatment of HIV infection. All regimens that are recommended for most starting HIV therapy contain an integrase inhibitor, while non-nucleosides and protease inhibitors are to be considered only in certain clinical situations. Of these integrase inhibitors, bictegravir can be expected to become an important addition and, along with dolutegravir, will be a dominant agent in this dominant class.

The co-formulation of bictegravir with TAF and FTC will make it attractive as initial therapy, as well as a switch-to regimen. It is easy to imagine those taking elvitegravir (Vitekta) and cobicistat (Tybost) being convinced to swap integrase inhibitors and eliminate the pharmacological booster to reduce the risk of drug interactions and maybe improve lipids. The bictegravir fixed-dose combination will also be a much smaller tablet than the single-tablet formulation of dolutegravir, ABC, and 3TC.

As described below, the novel dual combination of dolutegravir and 3TC might become a thing. However, until more data are available to support this minimal approach and prescribers and patients jump on the dual-therapy bandwagon, the bictegravir/TAF/FTC tablet might really become the antiretroviral regimen "to rule them all."

Top 10 Clinical Developments of 2017
0. Introduction
1. The Cost of Cuts in HIV Spending
2. Awakening to the Opioid Crisis
3. Does It Work to Pay People to Come to Clinic?
4. Bictegravir -- It's Coming
5. A Better Second Chance
6. More Real World Test for Dual Antiretroviral Therapy
7. Heart Attacks in HIV Often Not Due to Atherosclerosis
8. How Long for Long-Acting Antiretrovirals?
9. ART Resistance Spreads
10. We Order Too Many CD4 Cell Counts, but Should We Really Stop?

David Alain Wohl, M.D., is a professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC). He is site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, director of the North Carolina AIDS Education and Training Center (AETC), and co-directs HIV services for the North Carolina state prison system. In 2014, he became co-director of the UNC-Duke Clinical RM Ebola Response Consortium.