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Islatravir + lenacapavir once weekly

Islatravir is an experimental nucleoside reverse transcriptase translocation inhibitor (NRTTI). Lenacapavir is an approved drug that belongs to a class called capsid inhibitors.

Researchers are testing the combination of islatravir + lenacapavir, both drugs given once weekly in oral formulations. In one study, researchers gave 106 participants the following regimens:

  • islatravir 2 mg + lenacapavir 300 mg – both drugs once weekly
  • Biktarvy – one pill once daily containing bictegravir + TAF (tenofovir alafenamide) + FTC (emtricitabine)

After 48 weeks all participants would take islatravir + lenacapavir.

The average profile of participants upon study entry was as follows:

  • age – 40 years
  • 82% male at birth, 18% female at birth; 1 transgender female and 1 non-binary person
  • major ethno-racial groups: White – 50%; Black – 36%
  • CD4+ count – 786 cells/mm3
  • viral load – at screening for study eligibility, all but one participant had a suppressed viral load (less than 50 copies/mL) on a standard-of-care oral regimen

Results

Interim results after 24 weeks are available for most participants. In total, 94% of participants on each regimen had suppressed HIV.

One person taking islatravir + lenacapavir had a viral load of 241 copies/mL prior to initiating the regimen, and at week 24 their viral load was 64 copies/mL. By week 30, their viral load had fallen to less than 50 copies/mL and they remain in the study. This person has no detectable resistance to the study drugs and levels of medicines in their blood are adequate for suppressing HIV.

Adverse events

Overall, more adverse events occurred in people who were taking islatravir + lenacapavir (17%) compared to Biktarvy (6%). However, all adverse events were mild or moderate in severity.

Noteworthy: Two people taking islatravir + lenacapavir had dry mouth and nausea. However, these issues were not severe.

Abnormal lab test results were generally mild and slightly more common in people taking islatravir + lenacapavir (five people) than Biktarvy (four people). One person on the two-drug regimen had elevated levels of the liver enzyme ALT in their blood, but this occurred because they had developed hepatitis B virus (HBV).

CD4+ counts and lymphocyte levels remained stable regardless of which combination participants took. This is important because several years ago a study using high daily doses of islatravir found decreased lymphocyte and CD4+ cell counts occurred. It is reassuring that this was not an issue in the current study.

The study results are promising and support continued research with the combination of islatravir + lenacapavir taken once weekly.

—Sean R. Hosein

REFERENCE:

Colson A, Crofoot G, Ruane PJ, et al. Efficacy and Safety of Weekly Islatravir Plus Lenacapavir in PWH at 24 weeks: A Phase II Study. Conference on Retroviruses and Opportunistic Infections, March 3-6, 2024. Abstract 208.