Bictegravir Has Finally Arrived: A Top HIV Clinical Development of 2018

I had to double check that it really was earlier this year that bictegravir was U.S. Food and Drug Administration-approved. On Feb. 7, the approval of the fixed-dose formulation of bictegravir with tenofovir alafenamide fumarate and emtricitabine (Biktarvy, B/F/TAF) was announced -- but like my teenage child, it seems as if it has been around much longer.

Over these past months, this medication has come as close as any HIV drug ever has to being the default antiretroviral therapy -- something to be used unless a really good reason dictates otherwise. Its main attraction isn;t so much about what it does, but what it doesn't do: B/F/TAF does not contain a pharmacological booster, need HLA-B*5701 screening, have food requirements, or require avoidance by those living with active hepatitis B or people within certain CD4 or HIV RNA parameters.

Drug interaction-wise, B/F/TAF plays well with most meds that the average American might be prescribed. Plus, it is a single, small pill. Clinical trial data show it is just as good as abacavir/lamivudine/dolutegravir (Triumeq, ABC/3TC/DTG), but with less hassle and less nausea. Compared with F/TAF (Descovy)+DTG, it is practically indistinguishable, except it's a single tablet.

The downsides of this combo are few, but include the potential for the seemingly pan-integrase inhibitor neuropsychological issues, the potential for it to have similar neural tube defect risks as DTG (plus the general unknown safety of TAF in pregnancy), the potential for excess weight gain compared with other regimens, and the potential for a tad more drug interactions than with DTG. That's lot of "potentials" without a lot of data. And that gets at the major gripe about this medication: It is new and, therefore, does not have a long track record.

The Bottom Line

In many ways, B/F/TAF is the HIV med we have been waiting for, but it says a lot about where we have come to in HIV therapeutics that even this powerful and well-tolerated medication -- and to some extent its two-pill sibling DTG+F/TAF -- has not been met with more fanfare. It could be because its immediate predecessors were pretty OK: Most patients taking single-tablet regimens such as ABC/3TC/DTG or cobicistat-boosted elvitegravir/F/TAF (Genvoya), and even many boosted protease inhibitor-based regimens, have no complaints for the most part. Meanwhile, even though getting off the ABC or the booster may offer theoretical benefits, those benefits do not always feel so obvious to the people taking the medication.

Which returns us to the idea of what will it take to dislodge triple-drug therapy from HIV therapy's pole position? Perhaps it will be a pill such as DTG+3TC that contains less medicine, but if not, then it might well take something that isn't a pill. Long-acting injectable agents are the future, whether we know it and accept it or not. Until then, on the multiple-choice test of which antiretroviral to use in most patients starting HIV medications, if you guess B/F/TAF, chances are you will be right.

Top 10 Clinical Developments of 2018
0. Introduction
1. GEMINI and the Rise of Two-Drug HIV Therapy
2. Debate Over Dolutegravir in Early Pregnancy
3. Integrase Inhibitors and Weight Gain
4. PrEP and the Decline in New HIV Diagnoses
5. On-Demand Prevention in France
6. Bictegravir Has Finally Arrived
7. Abacavir, Platelets, and a Cardiovascular Verdict
8. African-American Men and HIV Treatment Outcomes
9. The Long-Acting Bandwagon
10. Designing HIV-Resistant People

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-director of HIV services for the North Carolina state prison system. In 2014, he became co-director of the UNC-Duke Clinical RM Ebola Response Consortium.