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Bictegravir + lenacapavir – an emerging duo

Bictegravir is an integrase inhibitor and is available in a pill called Biktarvy, which also contains TAF + FTC. Biktarvy is taken once daily and is generally well tolerated and highly effective against HIV.

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Lenacapavir impairs the activity of an HIV protein called the capsid. It is classed as a capsid inhibitor. Currently, lenacapavir is reserved for people with multidrug-resistant HIV. It is also being developed for HIV prevention.

Gilead Sciences, the manufacturer of both drugs, is testing a combination of bictegravir + lenacapavir, both drugs taken once daily. The idea behind this is to offer a simplified regimen for some people with HIV.

In a clinical trial, researchers enrolled participants who were on a complex HIV treatment (antiretroviral therapy, ART) regimen and randomly assigned them to one of the following combinations:

  • bictegravir 75 mg + lenacapavir 25 mg – 51 people
  • bictegravir 75 mg + lenacapavir 50 mg – 52 people

The remaining 25 participants stayed on their complex ART regimens.

All combinations were taken in pill form once daily.

Study details

The average profile of participants at the start of the study was as follows:

  • age – 60 years
  • 24% were female at birth and 76% were male at birth
  • major ethno-racial groups: White – 65%; Black – 31%; Asian – 4%
  • CD4+ count – 610 cells/mm3
  • length of time on ART – 27 years
  • presence of HIV that had some degree of resistance to previous treatments – 81%

Prior to the study, participants were all on complex ART regimens, as follows:

  • 41% were taking regimens that required twice-daily dosing
  • 27% were taking at least five pills of HIV medicines daily

 Examples of complex regimens that some participants took included the following:

  • darunavir + cobicistat + dolutegravir + TAF + FTC
  • darunavir + cobicistat + dolutegravir + etravirine or rilpivirine

Results

After one year, the following proportions of participants had a suppressed viral load:

  • bictegravir 75 mg + lenacapavir 25 mg – 92%
  • bictegravir 75 mg + lenacapavir 50 mg – 90%
  • complex ART – 100%

CD4+ cell counts increased modestly over the course of the study and were similar among the three groups. 

Two people taking bictegravir + lenacapavir 25 mg had temporarily detectable viral loads, but they resuppressed while remaining on this combination.

Adverse events

Adverse events that led to premature study discontinuation:

  • bictegravir + lenacapavir 25 mg – mild but persistent nausea
  • bictegravir + lenacapavir 50 mg – severe nausea due to a pre-existing condition

One person who was taking lenacapavir at the 50 mg dose died from cardiovascular disease; this was unrelated to the study medicines.

Diarrhea seemed to be the most common adverse effect and was distributed as follows:

  • bictegravir + lenacapavir 25 mg – 10% had diarrhea
  • bictegravir + lenacapavir 50 mg – 4% had diarrhea
  • complex ART – 4% had diarrhea

Most cases of diarrhea were mild to moderate.

Higher doses of lenacapavir were not linked to increased side effects.

A pill containing bictegravir 75 mg and lenacapavir 50 mg has been developed and will be tested in larger clinical trials in the future. If such trials yield successful results, a pill containing both drugs could be approved for use in several years.

—Sean R. Hosein

REFERENCE:

Mounzer K, Slim J, Ramgopal M, et al. Efficacy and safety of bictegravir plus lenacapavir: 48-week outcomes in virologically suppressed people with HIV-1 on complex antiretroviral regimens at baseline. 25th International Conference on AIDS, Munich, Germany, 22-26 July 2024. Abstract OAB2602.