Drug Interactions in Lenacapavir-Based Long-Acting Antiviral Combinations

Viruses. 2022 May 31;14(6):1202. doi: 10.3390/v14061202.


Long-acting (LA) anti-HIV regimens show promise for increasing dosing intervals and consequently, improving the patients' quality of life. The first FDA-approved LA therapy is Cabenuva, which comprises rilpivirine (a non-nucleoside reverse transcriptase inhibitor) and cabotegravir (integrase strand transfer inhibitor). Novel promising LA anti-HIV agents such as lenacapavir (a capsid-targeting antiviral) and islatravir (EFdA, a nucleoside reverse transcriptase translocation inhibitor) need to be explored as combination therapies. Therefore, we sought to determine whether combination of lenacapavir with islatravir, rilpivirine, or cabotegravir displayed synergy, additivity, or antagonism. We performed dose-response matrices of these drug combinations in an HIV-1 reporter cell line and subsequently analyzed the data with SynergyFinder Plus, which employs four major drug interaction models: highest single agent, Bliss independence, Loewe additivity, and zero interaction potency. Most of these models predict additive inhibition by the studied drug combinations This work highlights the importance of effective drug combinations in LA-regimens.

Keywords: EFdA; islatravir; long-acting regimens; synergy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Drug Combinations
  • Drug Interactions
  • HIV Infections* / drug therapy
  • Humans
  • Quality of Life
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Rilpivirine / pharmacology
  • Rilpivirine / therapeutic use


  • Anti-HIV Agents
  • Drug Combinations
  • Reverse Transcriptase Inhibitors
  • cabotegravir, rilpivirine drug combination
  • Rilpivirine