Switching to Biktarvy from a protease inhibitor–based regimen

When used as part of combination HIV therapy (ART), the class of drugs called integrase inhibitors has potent anti-HIV activity and is generally well tolerated. As a result, more doctors are prescribing integrase inhibitors and more patients are using them.

Bictegravir is a new integrase inhibitor and is supplied as part of an entire regimen in one pill called Biktarvy. Other medicines in Biktarvy are TAF (tenofovir alafenamide) and FTC (emtricitabine). This pill is taken once daily with or without food, day or night.

In one study, researchers in Canada and other countries recruited adults who were taking regimens based on protease inhibitors and whose viral loads were undetectable. Participants were randomly assigned to receive either Biktarvy (290 people) or to continue with their protease inhibitor–based regimen (287 people). At the 48th week of the study, nearly all participants continued to maintain an undetectable viral load. In general, rates of side effects were similar regardless of the regimen used, although headache was more common in Biktarvy users.

Study details

The average profile of participants upon entering the study was as follows:

  • 83% men, 17% women
  • age – 48 years
  • major ethno-racial groups: white – 66%; black – 27%; Asian – 2%; Indigenous – 1%
  • CD4+ count – 620 cells/mm3
  • 83% were free from symptoms related to HIV disease
  • hepatitis B virus (HBV) co-infection – 3%
  • hepatitis C virus (HCV) co-infection – 2%
  • eGFR (estimated glomerular filtration rate; a general measure of kidney health) – 105 mL/minute

Commonly used protease inhibitors included the following:

  • atazanavir (Reyataz)
  • darunavir (Prezista)

Each of these drugs was taken with a small dose of another anti-HIV drug called ritonavir. The purpose of ritonavir is to raise and maintain the concentration of the protease inhibitor in the blood so that once-daily dosing of atazanavir or darunavir is effective.

In addition to protease inhibitors, study participants also took the following combinations of anti-HIV drugs:

  • TDF (tenofovir disoproxil fumarate) + FTC (emtricitabine)
  • abacavir + 3TC

The study took place for 48 weeks.


At the 48th week of the study, the proportions of participants with an undetectable viral load (less than 50 copies/mL) were distributed as follows:

  • Biktarvy – 92%
  • protease inhibitor regimen – 89%

Also, at week 48, the proportions of participants with a viral load less than 20 copies/mL were distributed as follows:

  • Biktarvy – 86%
  • protease inhibitor regimen – 85%

These differences were not statistically significant. Analysis suggests that, overall, Biktarvy is similar in effectiveness as the leading protease inhibitor–based regimens.

Adverse events

In clinical trials, the term adverse events is used to describe the unfortunate occurrences that can happen. Some of these may be due to the underlying disease process, some to the study medicines and some have nothing to do with the study at all.

The proportions of participants with treatment-related adverse events were distributed as follows:

  • Biktarvy – 19%
  • protease inhibitor regimen – 2%

This difference between the two regimens was driven mostly by headache, distributed as follows:

  • Biktarvy – 12%
  • protease inhibitor regimen – 4%

Here is the distribution of some other side effects:


  • Biktarvy – 2%
  • protease inhibitor regimen – 0%


  • Biktarvy – 2%
  • protease inhibitor regimen – 0%


  • Biktarvy – 2%
  • protease inhibitor regimen – 0%

In general, most side effects were of mild to moderate intensity and resolved over time.

Focus on headache

According to the researchers, headache occurred within the first eight weeks of initiating therapy with Biktarvy. Headache was generally mild and gradually resolved in most participants.

By the 48th week of the study, participants who still reported headache were distributed as follows:

  • Biktarvy – 2%
  • protease inhibitor regimen – 1%

No one prematurely left the study because of headache.

Serious adverse events

The distribution of serious adverse events was as follows:

Biktarvy – two people taking this regimen had to prematurely leave the study because of the following issues:

  • rash – one person
  • schizophrenia – one person; investigation suggested that schizophrenia was related to exposure to Biktarvy

Protease inhibitor regimen –one person taking this regimen had to prematurely leave the study because of the following reasons:

  • bone fracture and kidney injury


Two deaths occurred during the study. One person taking Biktarvy was diagnosed with tumours in one lung that spread to the brain. One person taking a protease inhibitor regimen died from complications associated with head injury arising from violence. These deaths were unrelated to the study medicines.

Abnormal lab test results

Serious or very seriously abnormal blood test results were distributed as follows:

  • Biktarvy – 16%
  • protease inhibitor regimen – 29%

This difference occurred mainly because of elevated levels of the waste product bilirubin among protease inhibitor users. Such elevations can occur in atazanavir users.

eGFR levels decreased very modestly in people taking Biktarvy and remained stable in people taking protease inhibitors. More sophisticated assessments did not find any treatment-related kidney injury.

Participants who received Biktarvy had statistically significant decreases in the following assessments done on fasting blood samples:

  • total cholesterol
  • LDL-C (“bad” cholesterol)
  • triglycerides
  • ratio of total cholesterol to HDL-C (“good” cholesterol)

Such changes are not surprising because participants who received Biktarvy had previously been taking protease inhibitors, which can cause unfavourable changes to fatty substances in the blood. In contrast, as a class, integrase inhibitors are known to have neutral effects on lipids in the blood.

Bear in mind

The present study found that Biktarvy is an option for doctors and patients who want to consider moving away from HIV treatment based on protease inhibitors. Biktarvy is effective and generally safe. However, Biktarvy users can develop a mostly mild headache that gradually resolves.

—Sean R. Hosein


Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor–based regimens in virologically suppressed adults with HIV-1: 48-week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018; in press.