Weekly Oral Islatravir–Lenacapavir Noninferior to Daily HIV Therapy in Phase 3 Trial
Germany: A phase 3 international clinical trial has shown that a once-weekly oral combination of islatravir and lenacapavir is as effective as the standard once-daily bictegravir–emtricitabine–tenofovir alafenamide regimen in maintaining viral suppression in adults with HIV-1. The findings suggest that a weekly oral treatment option could offer greater flexibility while maintaining efficacy and a comparable safety profile.
The findings were published in The New England Journal of Medicine by Jürgen K. Rockstroh, Department of Medicine I, University Hospital Bonn, Germany, and colleagues.
Daily single-tablet antiretroviral therapy has significantly improved HIV care, but maintaining strict adherence remains challenging for many people living with HIV. Less frequent dosing strategies may help reduce treatment burden while preserving viral suppression. To evaluate this approach, researchers assessed the efficacy and safety of switching virologically suppressed adults from a once-daily regimen to a once-weekly oral combination of islatravir (ISL) and lenacapavir (LEN).
The phase 3, double-blind, randomized, active-controlled, noninferiority trial enrolled 607 adults with virologically suppressed HIV-1 across 12 countries. Participants who had maintained viral suppression for at least six months on once-daily bictegravir–emtricitabine–tenofovir alafenamide (B/F/TAF) were randomly assigned to switch to once-weekly oral islatravir–lenacapavir (ISL/LEN; 304 participants) or continue daily B/F/TAF (303 participants) for 96 weeks.
The primary endpoint was maintenance of viral suppression at 48 weeks. Overall, 21% of participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were aged 65 years or older.
Key findings from the study include:
- At 48 weeks, no participants receiving once-weekly ISL/LEN had an HIV-1 RNA level of 50 copies/mL or higher, compared with one participant (0.3%) in the once-daily B/F/TAF group.
- Viral suppression (HIV-1 RNA below 50 copies/mL) was maintained in 93.4% of participants receiving ISL/LEN and 92.4% of those continuing daily B/F/TAF, demonstrating that the weekly regimen was noninferior to standard daily therapy.
- CD4+ T-cell counts remained stable in both groups over 48 weeks, with no clinically meaningful differences between treatments.
- Treatment discontinuation due to adverse events occurred in 2.0% of participants receiving ISL/LEN and 1.7% of those receiving B/F/TAF.
- Serious adverse events were reported in 5.3% of the ISL/LEN group and 4.6% of the B/F/TAF group, indicating comparable safety profiles.
The researchers concluded that once-weekly oral islatravir–lenacapavir was noninferior to the standard once-daily bictegravir–emtricitabine–tenofovir alafenamide regimen in maintaining viral suppression among adults with virologically suppressed HIV-1. The comparable efficacy and safety observed over 48 weeks suggest that weekly oral therapy could become a promising alternative for people seeking less frequent dosing, potentially reducing treatment burden while maintaining effective long-term HIV control.
Reference:
DOI: 10.1056/NEJMoa2607973
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