TreatmentUpdate
222

October/November 2017 

Bictegravir + TAF + FTC vs. Triumeq

Triumeq is a complete HIV treatment in one pill, which contains the following medicines:

  • dolutegravir (Tivicay) + abacavir + 3TC

Bictegravir is an emerging integrase inhibitor that will likely be licensed in Canada by mid-2018.

In a randomized, placebo-controlled clinical trial with about 600 HIV-positive people who had not previously taken HIV treatment, researchers randomly assigned participants to receive one of the following regimens:

  • bictegravir + TAF (tenofovir alafenamide) + FTC
  • Triumeq

After one year, researchers found that both regimens were highly effective at suppressing HIV and helping to raise CD4+ cell counts. The proportions of participants who experienced side effects were similar with both regimens. However, nausea was more common among participants who took Triumeq (17%) compared to participants who took the bictegravir regimen (5%). The researchers say that this difference was probably due to the presence of abacavir in Triumeq.

Study details

Researchers enrolled participants from the following countries:

  • Canada
  • Dominican Republic
  • France
  • Germany
  • Italy
  • Spain
  • UK
  • United States

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

  • age – 32 years
  • 91% men, 9% women
  • 91% had no symptoms of HIV infection
  • HIV viral load – 30,000 copies/mL
  • CD4+ count – 450 cells/mm3
  • estimated glomerular filtration rate (eGFR – an assessment of kidney health) – 125 mL/min

This study is expected to last for up to three years; here we present results from the first year on 314 participants on a bictegravir regimen and 315 on a dolutegravir regimen.

Results—Changes in viral load and CD4+ cell counts

After one year, the proportions of participants with a viral load less than 50 copies/mL were distributed as follows:

  • bictegravir regimen – 92%
  • dolutegravir regimen – 93%

This difference was not statistically significant and therefore the bictegravir regimen could be considered to be roughly equivalent, or non-inferior, to the dolutegravir regimen.

When researchers analysed blood samples with a more sensitive viral load assay with a lower limit of 20 copies/mL, the proportions of participants with a viral load less than 20 copies/mL were as follows:

  • bictegravir regimen – 87.6%
  • dolutegravir regimen – 86.3%

This difference between the two regimens was not statistically significant.

CD4+ cell counts increased by about 230 cells/mm3 over the course of the study and were similar between the two regimens.

Adverse events

The term adverse events is used to describe a range of unfortunate events that can occur to participants during a clinical trial. Such events may be driven by the underlying disease process, the study drugs or circumstances that have nothing to do with the study (such as accidents).

In this study, researchers stated that, overall, “both [regimens] were well tolerated with most adverse events reported as mild or moderate in severity.”

Adverse effects that were bothersome or serious enough to cause people to leave the study prematurely occurred in four people (1%), all of whom were taking the dolutegravir regimen. These side effects were distributed as follows:

  • nausea and rash – one person
  • less-than-normal levels of platelets in the blood – one person
  • inflammation of the pancreas gland and excess fat in stools – one person
  • depression – one person

According to the researchers, in general, “central nervous system and psychiatric adverse events were evenly distributed between [regimens].” This point is important because there have been reports from individual physicians and observational studies that suggest that dolutegravir may be associated with the following side effects in some people (usually between 2% and 6%):

  • difficulty falling asleep and/or staying asleep
  • poor concentration
  • irritability
  • anxiety
  • depression

That the rates of such problems are similar between bictegravir and dolutegravir should not be surprising, as bictegravir is structurally similar to dolutegravir.

As mentioned earlier in this issue of TreatmentUpdate, phase III clinical trials tend to enroll people who are relatively well and who are likely to stay on the study medications. However, once a drug is approved and begins to be widely used in the community by patients who have health issues (in addition to HIV infection), more side effects may be reported. A future issue of TreatmentUpdate will explore reports of possible side effects, particularly mental health issues, associated with integrase inhibitors.

No one died during this study.

Rates of common side effects (graded as mild or moderate) were as follows:

Nausea

  • bictegravir regimen – 10%
  • dolutegravir regimen – 23%

Headache

  • bictegravir regimen – 11%
  • dolutegravir regimen – 24%

Diarrhea

  • bictegravir regimen – 13%
  • dolutegravir regimen – 13%

Difficulty falling asleep and/or staying asleep

  • bictegravir regimen – 4%
  • dolutegravir regimen – 6%

Unexpected tiredness

  • bictegravir regimen – 6%
  • dolutegravir regimen – 9%

Vomiting

  • bictegravir regimen – 4%
  • dolutegravir regimen – 5%

Bone mineral density (BMD)

People with HIV infection are at increased risk for thinner-than-normal bones (reduced BMD). Furthermore, upon initiation of combination therapy (ART), BMD tends to decrease by about 2% to 4% and then stabilize after a year or two. The reasons for this are not yet clear.

In the present study BMD decreased by an average of 1% in participants after one year. There were no significant differences in the change in BMD between the two regimens.

Kidneys

No participants developed serious kidney injury. Complex assessments of kidney health did not detect any subtle kidney injury, attesting to the safety of the study regimens.

Lipids—Cholesterol and triglycerides

There did not appear to be any clinically significant differences in lipid levels between the two regimens.

Bear in mind

According to the researchers, regimens based on bictegravir or dolutegravir have several advantages, including the following:

  • When used with two nucleoside analogues they are generally effective at lowering viral load.
  • They do not need a boosting agent such as cobicistat (found in Genvoya and Stribild) or ritonavir.
  • They are available as a complete treatment in one pill.

As mentioned elsewhere in this issue of TreatmentUpdate, some researchers have noted that the combination of bictegravir + TAF + FTC offers the following advantages:

  • It contains two anti-hepatitis B drugs (TAF and FTC) in one pill, which should be useful for people co-infected with HIV and hepatitis B virus.
  • There is no need for pre-treatment testing for hypersensitivity (in the case of regimens containing abacavir, such as Triumeq, testing for hypersensitivity to abacavir must first be performed to assess the risk of this problem occurring).

For the future

  • A single pill containing bictegravir + TAF + FTC should be approved in Canada in the summer of 2018.
  • A clinical trial of bictegravir + TAF + FTC is underway in HIV-positive women.
  • Results of bictegravir in treatment-experienced people should become available in the months ahead.

—Sean R. Hosein

REFERENCE:

Gallant J, Lazzarin A, Mills A, et al. 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; in press.