Biktarvy, a new HIV combo pill recently approved by the FDA
This week, the FDA granted approval of Gilead Science’s single-tablet combo pill of bictegravir, emtricitabine (FTC) and tenofovir alafenamide (TAF) named Biktarvy.
Read on for additional information about what we know about this new combo pill, and why it will be a welcome addition to the growing number of integrase inhibitors available as treatment for people living with HIV.
Prime time for integrase inhibitors
Integrase inhibitors such as raltegravir, elvitegravir and dolutegravir are now a standard part of first-line HIV therapy because they are potent agents that reduce viral loads quickly and are generally well-tolerated. The recently-approved combo pill, Biktarvy, contains a new integrase inhibitor, called bictegravir. This past summer, we learned results from two phase 3 trials on bictegravir (GS-9883, Gilead Sciences).
Study # 1: Bictegravir versus dolutegravir
This study compared bictegravir to another integrase inhibitor (dolutegravir), and demonstrated that bictegravir worked as well to suppress viral loads when combined with a commonly-used NRTI backbone as dolutegravir when combined with that same NRTI backbone.
A total of 645 people who were treatment naïve (i.e., had not started HIV medications yet) were included in the study. Everyone in this phase 3 study took the same nucleoside reverse transcriptase inhibitor (NRTI) backbone: tenofovir alafenamide (TAF; 25 mg) plus emtricitabine (FTC; 200 mg), which is Descovy®, with either dolutegravir (50 mg) or bictegravir (50 mg).
A substantial group of participants (19%) had high viral loads, which were greater than 100,000 copies/mL. 12% had low CD4 cell counts below 200 cells/mm3. The majority of study participants were white (59%), men (88%), resided in the U.S. (60%) and were men who had sex with men (76%).
After 48 weeks of therapy, 89% of people in the bictegravir group (286 people) had undetectable viral loads less than 50 copies/mL. In the dolutegravir group, 93% of people (302 people) were virally suppressed after 48 weeks. This 3.5% difference between the groups was within the range of demonstrating “non-inferiority” of bictegravir to dolutegravir.
The most common adverse effects experienced by participants in the bictegravir group were headache (13%), diarrhea (12%) and nausea (8%) while the most common adverse effects in the dolutegravir arm were also headache (12%), diarrhea (12%) and nasopharyngitis (which is swelling of the nasal passages, usually from a cold; 10%). Kidney function and cholesterol values were comparable between the groups at the 48 week time point.
Study # 2: A tale of two single tablet regimens
The second study pitted the single tablet regimen of bictegravir (50 mg), TAF (25 mg) and FTC (200 mg) against a single tablet with dolutegravir (50 mg), abacavir (600 mg) and lamivudine (300 mg), which are the drugs in Triumeq. The study found that both regimens were similarly effective in helping people to suppress their viral loads but that far fewer people experienced diarrhea taking the bictegravir regimen.
The study included 631 treatment naïve participants who were HLA-B*5701 negative (did not have an allergy to abacavir), were not infected with hepatitis B and had good baseline kidney function. Participants also were tested for drug resistance, and people enrolled did not have resistance mutations against the drugs used it he study. A small proportion of enrollees had high baseline HIV viral loads greater than 100,000 copies/mL (16%) or low CD4+ cell counts below 200 cells/mm3 (11%).
After 48 weeks, 92% of participants on the bictegravir regimen had undetectable viral loads (<50 copies/mL). A similar percentage of people taking the dolutegravir regimen (93%) also had an undetectable viral load after 48 weeks, demonstrating that the bictegravir single-tablet regimen was not inferior to the single-tablet dolutegravir regimen.
About a quarter of people (23%) taking the dolutegravir regimen experienced diarrhea during the study (13% of people taking the bictegravir regimen experienced diarrhea). A slightly higher percentage of people taking the dolutegravir regimen experienced headache (14%) than people in the bictegravir group (11%). The percentage of people experiencing nausea were similar between the groups (~10% of people).
There were no significant differences in hip and spine bone mineral density, kidney function changes or cholesterol changes between the two treatment groups.
What does this mean for people living with HIV?
These two studies show that the new integrase inhibitor bictegravir is comparable to the already available integrase inhibitor dolutegravir, when combined with commonly used NRTIs, in people who are just beginning HIV therapy.
Regimens with bictegravir and dolutegravir are similarly robust at lowering HIV viral load, generate few (if any) resistance mutations if the treatment does not work, and seem to be generally well-tolerated (although the side effect of diarrhea may be higher with dolutegravir/abacavir/lamivudine).
Biktarvy will be one more option for people who are new to HIV therapy and are allergic to abacavir. The other integrase single tablet regimen options for people allergic to abacavir are elvitegravir/cobicistat/F/TAF (Genvoya®) or elvitegravir/cobicistat/F/tenofovir disoproxil fumarate (Stribild®).
There are not any clinical studies examining how well bictegravir therapies work for treatment-experienced people, for women (although there is a study currently being conducted), or for people who are pregnant.
There also are not any large “switching” studies showing how well bictegravir therapies work for people already on current HIV therapy, although switching to a therapy with Biktarvy may be appropriate for people who are experiencing side effects with their current regimen. (Your HIV provider will be able to offer more specific guidance that’s relevant to your health and needs.)
Jennifer Cocohoba, PharmD, is an associate clinical professor in the School of Pharmacy at the University of California, San Francisco (UCSF). Since 2004, she has worked as the clinical pharmacist for the UCSF Women’s HIV Program, where she provides adherence support and medication information to patients and providers.
Sax, P. E. and colleagues. 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.
Gallant J. and colleagues. 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.