Long-acting injectable HIV therapy when adherence is the problem

Design

Phase 3b, randomised, open-label, non-inferiority trial

Population

540 adults with suppressed 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); failure 1.9% vs 0%

The IMPALA trial in NEJM (15 October) randomised 540 adults in Kenya, South Africa and Uganda with suppressed HIV but documented adherence or engagement problems. They either switched to cabotegravir plus rilpivirine injections every eight weeks or stayed on 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, which met non-inferiority. But confirmed virological failure occurred in five people (1.9%) on injections and none on tablets. Serious adverse events were similar.

This is the population for whom long-acting therapy was always expected to matter, and it was tested where resistance testing is often unavailable. The trade-off is clear: equal suppression overall, with a small number of failures on a regimen that can leave resistance to two drug classes. For India, the regulatory status and availability of this regimen are not established here; its main relevance is to how future programmes are designed.

• Consider long-acting cabotegravir plus rilpivirine for suppressed patients who struggle with daily tablets
• Expect overall suppression similar to oral dolutegravir at one year
• Discuss the small excess of virological failure, which can leave two-class resistance
• Keep visits on schedule; missed injections are the main route to failure
• Where resistance testing is available, check history for prior rilpivirine resistance

Why it matters

It challenges the assumption that long-acting therapy is only for the most adherent patients.

Don't overread it

Only 48 weeks of follow-up; the five failures are too few to judge longer-term resistance risk.

The statistics, in plain English

Non-inferiority was met because the lower bound of the difference (−3.1 points) stayed well above the −10 margin. The failure difference of 1.9 points (95% CI 0.3 to 3.5) excludes zero, so the excess is real, if small — about one extra failure per 50 patients.

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