Combination Therapy with Lenacapavir and Broadly Neutralizing Antibodies Shows Promise in HIV Treatment

Strategic Insights -

The European AIDS Treatment Group has published promising results from a phase 2 trial combining lenacapavir (LEN) and two broadly neutralizing antibodies (bNAbs), teropavimab (TAB) and zinlirvimab (ZAB). The study, presented at EACS 2025, found that this combination produced a slightly lower average increase in CD4+ counts compared to a stable baseline daily oral antiretroviral regimen (SBR), but maintained a consistent viral load of less than 50 copies/mL in most participants. The results, which have been observed up to 52 weeks, are a significant step forward in HIV treatment research.

Key Takeaways:

  • The combination of lenacapavir and two broadly neutralizing antibodies (teropavimab and zinlirvimab) produced a slightly lower average increase in CD4+ counts compared to a stable baseline daily oral antiretroviral regimen (SBR) (10 cells/mcL vs. 53 cells/mcL).
  • The combination maintained a consistent viral load of less than 50 copies/mL in most participants (97% in the LEN/TAB/ZAB group and 100% in the SBR group).
  • The study enrolled an average of 51-year-old participants, with 15% identifying as female and 36% identifying as Black, and a mean CD4+ count of 748 cells/mcL.
  • The combination showed a low rate of adverse events (AEs), with only 30/36 AEs being grade 1 (mostly injection site reactions related to subcutaneous lenacapavir).
  • The researchers plan to continue studying the combination and expect it to be the first bNAb treatment available for patients if phase 3 is successful.

Statistics:

  • The study enrolled 53 participants in the LEN/TAB/ZAB group and 27 participants in the SBR group.
  • The mean CD4+ count in the study was 748 cells/mcL.
  • The viral load in the LEN/TAB/ZAB group was less than 50 copies/mL in 97% of participants at week 52.
  • The rate of adverse events (AEs) was low, with only 30/36 AEs being grade 1.
  • The combination resulted in a mean increase in CD4+ count of 10 cells/mcL (SD, 208) in the LEN/TAB/ZAB group and 53 cells/mcL (SD, 124) in the SBR group.

Sources:

  • European AIDS Treatment Group (2025). Combining lenacapavir and two broadly neutralizing antibodies shows promise in HIV treatment. Presented at EACS 2025.
  • ClinicalTrials.gov (2023). A Study to Evaluate the Safety and Efficacy of Lenacapavir (LEN) Plus Teropavimab (TAB) and Zinlirvimab (ZAB) in Participants With HIV-1 Infection (NCT05729568).
  • Infectious Disease Special Edition (2025). Gilead's LEN/TAB/ZAB Combination Therapy Shows Promise in HIV Treatment.