US regulators approve new HIV combo pill containing bictegravir

The US Food and Drug Administration (FDA) yesterday approved Biktarvy, Gilead Sciences' new single tablet antiretroviral regimen containing the HIV integrase inhibitor bictegravir, which was highly effective and well tolerated in clinical trials.

Biktarvy is the first fixed-dose combination pill to include bictegravir, which does not require pharmacokinetic boosting, unlike Gilead's earlier integrase inhibitor elvitegravir (Vitekta, also in the Stribild and Genvoya combinations). This avoids the drug-drug interactions that can occur with the boosters ritonavir or cobicistat, which can affect the way many drugs are processed in the liver.

Bictegravir is combined with two nucleoside/nucleotide reverse transcriptase inhibitors: emtricitabine and tenofovir alafenamide (TAF), the new kidney- and bone-friendly formulation of tenofovir.


integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.

Food and Drug Administration (FDA)

Regulatory agency that evaluates and approves medicines and medical devices for safety and efficacy in the United States. The FDA regulates over-the-counter and prescription drugs, including generic drugs. The European Medicines Agency performs a similar role in the European Union.

virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

hepatitis B virus (HBV)

The hepatitis B virus can be spread through sexual contact, sharing of contaminated needles and syringes, needlestick injuries and during childbirth. Hepatitis B infection may be either short-lived and rapidly cleared in less than six months by the immune system (acute infection) or lifelong (chronic). The infection can lead to serious illnesses such as cirrhosis and liver cancer. A vaccine is available to prevent the infection.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

Biktarvy is indicated both for adults starting HIV treatment for the first time and for people on treatment with an undetectable viral load who wish to switch to a new regimen that might be more convenient or better tolerated. Biktarvy is a single pill taken once daily with no food requirements, and it is the smallest three-drug tablet on the market containing an integrase inhibitor, according to Gilead.

The other existing integrase inhibitor-based single-tablet regimens are ViiV Healthcare's Triumeq (dolutegravir/abacavir/lamivudine) and the two-drug Juluca (dolutegravir/rilpivirine). Triumeq requires testing for the HLA-B*5701 genetic variation, which increases the risk of hypersensitivity to abacavir. Juluca was approved by the FDA in November but is not yet approved by the European Medicines Agency.

FDA approval of Biktarvy was based on data from four ongoing phase 3 clinical trials. Two studies compared bictegravir versus dolutegravir in triple regimens for previously untreated people, using either separate tablets (Study 1490) or single-tablet combination pills (Study 1489). They found that bictegravir was non-inferior to dolutegravir, with around 90% of study participants achieving viral suppression at 48 weeks using either regimen.

Two other studies evaluated bictegravir in people who were virally suppressed on their current treatment. Study 1878 showed that people who switched from a boosted protease inhibitor to Biktarvy were as likely to maintain an undetectable viral load as those who stayed on their existing regimen­ – again around 90% in both arms. Results from Study 1844 will be presented at an upcoming conference, Gilead said.

These studies showed that Biktarvy was generally safe and well tolerated. The most common adverse events were headache and diarrhoea.

Because it contains TAF instead of the older tenofovir disoproxil fumarate (TDF), Biktarvy is less likely to cause bone loss or kidney problems. Nonetheless, kidney function should be tested before starting Biktarvy and monitored regularly. No dosage adjustment of Biktarvy is necessary for people with an estimated creatinine clearance of 30 ml/min or greater, the cut-off for moderate (stage 3) chronic kidney disease, according to Gilead. Across the four trials, no participants developed proximal renal tubulopathy or Fanconi syndrome and no one discontinued treatment due to kidney-related side-effects. 

People considering Biktarvy should be tested for hepatitis B virus (HBV) infection before starting because the TAF component is active against HBV as well as HIV, and stopping treatment could result in hepatitis flare-ups.

Biktarvy is currently being evaluated in a women-only trial and in a study of children and adolescents, Gilead said.

"In clinical trials through 48 weeks, no patients taking the regimen of bictegravir plus [emtricitabine]/TAF developed treatment-emergent resistance, results that were observed both in people new to therapy and those who were virologically suppressed and chose to switch regimens," Dr Paul Sax of Brigham and Women’s Hospital in Boston said in a Gilead press release. "In addition, the clinical data show that the regimen’s antiviral efficacy, tolerability profile and limited drug interactions offer an effective new treatment option for a range of people living with HIV."


Gilead Sciences. U.S. Food and Drug Administration Approves Gilead's Biktarvy (Bictegravir, Emtricitabine, Tenofovir Alafenamide) for Treatment of HIV-1 Infection. Press release. 7 February 2018.