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Emerging experimental treatment – bictegravir + lenacapavir

Biktarvy is a pill containing the following anti-HIV drugs:

  • bictegravir – an integrase inhibitor
  • FTC (emtricitabine) – a nucleoside analogue
  • TAF (tenofovir alafenamide) – a nucleoside analogue

The combination of drugs in Biktarvy is generally well tolerated and effective against HIV. Biktarvy is a complete regimen in a pill and is taken at a dose of one pill daily with or without food.

Reducing exposure to drugs

Until there is a cure, people with HIV will have to take treatment on a regular basis in order to keep the virus suppressed and stay healthy. Since 1996, the standard of care has been a combination of three drugs. Back then, attempts at reducing the burden of medicines taken by people with HIV failed largely because treatments used were not as effective as those that are available today.

In the past five years, the pharmaceutical company ViiV Healthcare has developed regimens consisting of two drugs that have proven to be highly effective in clinical trials. The first pill containing a two-drug regimen was Juluca—dolutegravir + 3TC (lamivudine). The second pill containing another complete regimen was Dovato—dolutegravir + 3TC.

Subsequently, ViiV developed another regimen, a long-acting injectable called Cabenuva that consists of two drugs—cabotegravir + rilpivirine.

Given the lifelong burden of HIV treatment, it is plausible that a two-drug regimen may be beneficial.

Lenacapavir

The pharmaceutical company Gilead Sciences (maker of Biktarvy, TAF and FTC) has developed lenacapavir (Sunlenca), which belongs to a class of drugs called capsid inhibitors.

After initial oral dosing for approximately two weeks, lenacapavir can be injected every six months. It was originally developed to be part of combination therapy with other drugs taken orally, as there is currently no drug with which it can be partnered for injection every six months. As it has to be injected over the long term and currently available drug combinations work for most people, lenacapavir is reserved mainly for highly treatment-experienced people who have HIV that is resistant to several drugs. In other words, it is not a commonly used HIV treatment.

Bictegravir + lenacapavir

Spurred by the success of other two-drug regimens, Gilead is developing a two-drug regimen consisting of bictegravir + lenacapavir, to be taken orally.

A clinical trial (NCT 05502341) with this combination is underway in several countries in people with HIV. Participants recruited for this study have been taking a complex regimen either because of a history of drug-resistant HIV or because they have an intolerance to some other therapies (and therefore reduced treatment options).

The trial has a complex design, but after a two-day loading dose of lenacapavir, most participants will get a combination of bictegravir at a dose of 75 mg per day with lenacapavir dosed at 25 mg or 50 mg per day. The remaining participants will remain on their pre-study regimen.

If the combination of bictegravir + lenacapavir is successful, it will likely be approved for treatment. The combination could become an option for people with multidrug-resistant HIV or for people whose doctors want to prescribe a nucleoside-free regimen.

—Sean R. Hosein

REFERENCE:

Doan J, Brunzo-Hager S, Satterly B, et al. Expanding therapeutic options: lenacapavir + bictegravir as a potential treatment for HIV. Expert Opinion on Pharmacotherapy. 2023 Sep-Dec;24(18):1949-1956.