Biktarvy is a new regimen in one pill containing the following anti-HIV drugs:
- bictegravir -- 50 mg
- TAF (tenofovir alafenamide) -- 25 mg
- FTC (emtricitabine) -- 200 mg
Of these three drugs, bictegravir is new. It belongs to a class of anti-HIV drugs called integrase inhibitors. Leading treatment guidelines in high-income countries recommend initiating combination treatment with an integrase inhibitor, as these drugs are generally well tolerated and highly effective. Integrase inhibitor combinations are also recommended for second-line use.
In the past eight years, most pivotal (phase III) clinical trials of integrase inhibitors have not had large proportions of HIV-positive women. Pharmaceutical companies have subsequently conducted trials that enrolled only women who were then given integrase inhibitor-based combination therapy.
In a trial overseen by Gilead Sciences, the manufacturer of Biktarvy, researchers in several countries recruited 470 women who were taking HIV treatment (ART) and whose viral loads were suppressed (less than 50 copies/mL) and randomly assigned them to either continue on their present regimen or to switch to Biktarvy. After 48 weeks the study found that Biktarvy was similarly effective and well tolerated as the women's other regimens. Rates of side effects in women taking Biktarvy were relatively low. There were a small number of pregnancies with no apparent ill effects of Biktarvy on the infant. However, larger studies will be needed before researchers can be certain about the safety of Biktarvy during pregnancy.
Researchers in several countries recruited women for this study (the countries are listed in decreasing order of the number of women enrolled):
- Russian Federation
- United States
- Dominican Republic
The average profile of women upon entering the study was as follows:
- age -- 40 years
- major ethno-racial groups: black -- 37%; white -- 36%; Asian -- 21%; Hispanic -- 16%
- CD4+ count -- 700 cells/mm3
- 90% of women did not have symptoms of HIV disease
- eGFR (estimated glomerular filtration rate; an assessment of overall kidney health) -- 100 mL/min
Most participants (95%) were taking one of the following single-tablet regimens:
- Genvoya (elvitegravir + cobicistat + TAF + FTC)
- Stribild (elvitegravir + cobicistat + TDF + FTC)
TDF (tenofovir disoproxil fumarate) is the older formulation of tenofovir that can cause kidney injury and thinner bones in some people. TAF is the newer formulation of tenofovir that is generally safer.
At the 48th week of the study, the proportions of participants with an undetectable viral load (less than 50 copies/mL) were as follows:
- Biktarvy -- 96%
- other regimens -- 95%
Statistical analysis found that the effectiveness of Biktarvy was similar to the other regimens. The technical term for this is "non-inferior."
None of the participants developed resistance to the drugs in Biktarvy.
Three women stopped taking Biktarvy; they left the study and switched to other regimens.
The term adverse events refers to the unfortunate events that can sometimes occur in a clinical trial. Some of these events may be due to drug side effects, some may be caused by the underlying disease process and some may have nothing to do with the clinical trial.
According to the study protocol, women who became pregnant while taking Biktarvy were supposed to leave the study and change their regimen to one chosen by their doctor. The other women in the study who were not taking Biktarvy and who became pregnant were given a regimen chosen by the study researchers.
The pregnancies in the study were distributed as follows:
- Biktarvy -- five pregnancies (one live birth, two abortions and the outcome of the other two pregnancy outcomes were not yet documented)
- other regimens -- seven pregnancies (two live births, two miscarriages, one ongoing pregnancy and two pregnancy outcomes not yet documented)
There were no reported birth defects in either group. However, the study was not designed to assess the safety of Biktarvy during and after pregnancy. Information about Biktarvy's safety during pregnancy will take many years to accumulate. Such information will be obtained from case reports and other studies.
There were no significant differences between the regimens when it came to eGFR results. Other, more complex assessments of kidney health showed only modest improvements, particularly in women who had been previously taking the older formulation of tenofovir (TDF) and who switched to TAF (as part of Biktarvy) when they entered the study.
Other Adverse Events
Most adverse events reported in the study were of mild to moderate intensity. Adverse events that were judged to be related to the drugs used in the study included the following:
- Biktarvy -- two cases each of anemia; two cases of nausea and vomiting; one case each of headache, feeling sleepy during the daytime, diarrhea, type 2 diabetes, pre-diabetes, anxiety, sleeping problems, and an unspecified "emotional disorder"
- other regimens -- one case each of higher-than-normal levels of the waste product bilirubin in the blood, depression, and bone/joint pain
There was one death in the study, which occurred in someone who was taking a non-Biktarvy regimen. The death occurred because of complications from a severe flu.
Bear in Mind
The findings from this study suggest that Biktarvy is generally safe in HIV-positive women. However, larger studies are needed to assess the safety of Biktarvy in pregnant women. Information for such studies may take years to accumulate, as Biktarvy is new and HIV-positive women may be cautious in their use of this single-tablet regimen because of concerns about potential adverse effects on the fetus.
Kityo C. Hagins D, Koenig K, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide in women. Conference on Retroviruses and Opportunistic Infections, 4-7 March 2018. Boston, Massachusetts. Abstract 500.
[Note from TheBodyPRO: This article was originally published by CATIE in Aug. 2018. We have cross-posted it with their permission.]