- Design
- Phase 3b open-label randomised non-inferiority trial
- Population
- 537 suppressed adults with HIV-1 and adherence challenges in Kenya, South Africa and Uganda
- Primary outcome
- Viral load <50 copies/mL at week 48
- Effect
- 91.0% vs 89.2%; difference 1.9 points (95% CI −3.1 to 6.9)
IMPALA, an open-label phase 3b trial at seven sites in Kenya, South Africa and Uganda, randomised 540 adults with HIV-1 who were virally suppressed but had documented adherence or engagement difficulties. They received cabotegravir 600 mg plus rilpivirine 900 mg by injection every 8 weeks, or continued daily oral dolutegravir-based therapy. Baseline resistance testing was not done.
At 48 weeks, 91.0% on injections and 89.2% on tablets had a viral load below 50 copies/mL, a difference of 1.9 points that met non-inferiority. Confirmed virological failure occurred in five people on injections (1.9%) and none on tablets. Serious adverse events were similar.
Until now, long-acting injectable therapy was studied mostly in highly adherent people in well-resourced settings. This trial tested it in exactly the group it might help most, in an African programme setting, and it held up.
The failure signal deserves attention: rilpivirine resistance and integrase resistance can follow failure on injections, and without baseline testing some patients may have had pre-existing resistance. The drugs are not yet routinely available in India's national programme.
- Consider long-acting cabotegravir plus rilpivirine for suppressed patients who struggle with daily tablets, where it is available.
- Check viral load regularly after switching, since virological failure was more frequent on injections.
- Review previous regimens and any resistance results before switching, especially prior NNRTI exposure.
- Plan injection visits carefully; late injections risk low drug levels and resistance.
- Keep oral dolutegravir-based therapy as the standard where injectables are unavailable.
Why it matters
It extends long-acting HIV treatment to the people who most need an alternative to daily pills.
Don't overread it
Non-inferior suppression does not mean equal resistance risk; failures occurred only on injections.
The statistics, in plain English
Non-inferiority means the injectable regimen was not worse than tablets by more than the prespecified 10 points; the confidence interval (−3.1 to 6.9) lies well inside that margin. The virological failure difference (1.9 points, 95% CI 0.3 to 3.5) is small in absolute terms but just excludes zero.
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