ISLEND-1: weekly oral islatravir-lenacapavir held HIV suppression as well as a daily tablet

Design

Phase 3, double-blind, randomised, active-controlled noninferiority trial in 12 countries

Population

607 adults with HIV-1 suppressed for at least 6 months on daily treatment

Primary outcome

HIV-1 RNA of 50 copies per mL or higher at week 48 (noninferiority margin 4 percentage points)

Effect

0% vs 0.3%; difference -0.3 points (95% CI -1.4 to 0.8)

ISLEND-1 was a phase 3, double-blind, active-controlled, noninferiority trial in 12 countries. Adults with HIV-1 suppressed for at least 6 months on daily bictegravir-emtricitabine-tenofovir alafenamide were randomised 1:1 to switch to weekly oral islatravir-lenacapavir (304) or to stay on daily treatment (303), each with matching placebo.

At week 48, an HIV-1 RNA level of 50 copies per millilitre or higher occurred in no participants on the weekly regimen and in 1 (0.3%) on the daily one (difference -0.3 percentage points, 95% CI -1.4 to 0.8), within the 4-point noninferiority margin. Suppression below 50 copies was 93.4% vs 92.4%. Serious adverse events occurred in 5.3% and 4.6%; discontinuations for adverse events were 2.0% and 1.7%.

The population was already suppressed, so this addresses switching, not starting treatment. Follow-up at 48 weeks of a planned 96 is short for a drug combination meant for decades of use.

• This trial studied switching people already suppressed on daily treatment, not starting therapy.
• Noninferiority was met at week 48; the regimen is not yet an option to prescribe from this trial alone.
• Adherence is the likely benefit, but the trial did not measure real-world adherence outside trial conditions.
• Check the regulatory status and availability with your HIV service before discussing it with patients.

Why it matters

Dosing frequency is one of the few remaining levers on adherence in long-term HIV care.

Don't overread it

The trial was sponsor-funded, ran 48 weeks of a planned 96, and enrolled people who were already stable.

The statistics, in plain English

Noninferiority means the new regimen was not worse than the standard by more than a pre-set margin, here 4 percentage points. The upper confidence limit of 0.8 sits well inside that margin, but noninferiority does not show the new regimen is better.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.