Two-monthly injections matched daily pills in people who struggle with adherence

Design

Phase 3b, open-label, randomised noninferiority trial (IMPALA)

Population

540 virally suppressed adults with HIV and suboptimal adherence, Kenya, South Africa and Uganda

Primary outcome

Viral load below 50 copies per mL at week 48

Effect

91.0% vs 89.2% (difference 1.9 points, 95% CI -3.1 to 6.9); confirmed virologic failure 1.9% vs 0%

IMPALA was a phase 3b, open-label, randomised trial in Kenya, South Africa and Uganda, funded by the manufacturer. It enrolled 540 adults with HIV who were virally suppressed but had suboptimal adherence or engagement with care. They received injectable cabotegravir plus rilpivirine every 8 weeks or continued oral dolutegravir-based therapy. Baseline drug-resistance testing was not done.

At 48 weeks, 91.0% of the injectable group and 89.2% of the oral group had a viral load below 50 copies per mL (difference 1.9 percentage points, 95% CI -3.1 to 6.9), meeting the noninferiority criterion of -10 points. Confirmed virologic failure occurred in 5 participants (1.9%) on injections and none on oral therapy (difference 1.9 points, 95% CI 0.3 to 3.5). Serious adverse events were 4.1% vs 3.0%.

For people who cannot reliably take daily tablets, injections held suppression as well as pills. The failures in the injectable group matter because of resistance risk, which is why the programme around the injection (visit tracking, resistance awareness) counts. Availability and cost in India are not addressed in the source, and the regulatory position here should be checked locally.

• Suppression below 50 copies per mL at week 48 was 91.0% with injections vs 89.2% with oral therapy.
• Confirmed virologic failure occurred in 5 people (1.9%) on injections and in none on oral therapy.
• Serious adverse events were similar (4.1% vs 3.0%).
• Consider long-acting injections for people who are suppressed but struggle with daily dosing, where they are available.
• Plan how missed injection visits will be traced, because gaps carry a resistance risk.

Why it matters

It tests long-acting treatment in the people it is most needed for, rather than in those already doing well on pills.

Don't overread it

The trial was open-label, manufacturer-funded and ran only 48 weeks, and baseline resistance was not tested.

The statistics, in plain English

Noninferiority means the injectable was not worse than oral by more than 10 percentage points; the lower end of the interval (-3.1) is well inside that margin. The virologic failure difference has an interval that excludes zero (0.3 to 3.5), so the small excess of failures on injection is probably real even though the numbers are low.

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.