Two-monthly injections beat daily tablets in adolescents with HIV

Design

randomised, open-label, multicentre, 96-week non-inferiority trial with superiority testing

Population

476 adolescents aged 12–19 with virologically suppressed HIV in Kenya, South Africa, Uganda and Zimbabwe; 98% vertically acquired

Primary outcome

two consecutive viral loads ≥50 copies/mL by week 96

Effect

0.9% (95% CI 0.0–2.2) with injectable vs 6.4% (3.7–9.8) with oral; difference −5.5% (99% CI −10.3 to −1.5), p = 0.0013

LATA recruited 476 adolescents aged 12 to under 20 from five clinics in Kenya, South Africa, Uganda and Zimbabwe, all virologically suppressed for more than a year with no previous treatment failure. They were randomised open-label to intramuscular cabotegravir-rilpivirine every eight weeks after a loading schedule, or to daily oral dolutegravir-lamivudine-tenofovir disoproxil fumarate. Of those enrolled, 98% had acquired HIV vertically and the median duration of previous antiretroviral therapy was 11.7 years — these were young people who had been taking tablets since infancy.

By week 96, two participants on injections had two consecutive viral loads of 50 copies/mL or higher (Kaplan-Meier estimate 0.9%, 95% CI 0.0 to 2.2) against 15 on tablets (6.4%, 3.7 to 9.8). The estimated difference was −5.5% (99% CI −10.3 to −1.5): non-inferiority was met and superiority then demonstrated (p = 0.0013). Serious adverse events were similar (hazard ratio 1.16, 0.54 to 2.51), as were grade 3 or higher events (HR 1.07, 0.62 to 1.83). Seven participants stopped the injectable permanently, two for drug-related adverse events including one serious hypersensitivity reaction. Four had injection-site reactions.

A superiority result in a maintenance trial usually means adherence, not pharmacology — and that is the point. For any clinician managing a long-term condition in adolescents, the finding is that a treatment taken for them reliably beats a treatment they must remember daily, even when the daily regimen is a single well-tolerated tablet.

• Consider long-acting injectable maintenance where daily adherence is the limiting factor, not the drug
• Ask adolescents on lifelong therapy about missed doses in terms of specific weeks, not in general
• Counsel about injection-site reactions and the need to attend every eight weeks without fail
• Note that participants had to be suppressed for over 12 months with no previous failure — this is not a salvage strategy

Why it matters

It reframes adherence as something a service can design around rather than something to counsel about.

Don't overread it

All participants were already suppressed with no history of failure — this says nothing about using injectables in uncontrolled disease.

The statistics, in plain English

This was designed as a non-inferiority trial, which asks only whether the new option is not unacceptably worse; superiority was tested afterwards and found, which is stronger. The 99% confidence interval of −10.3 to −1.5 excludes zero, so the advantage is unlikely to be chance. Open-label design means participants knew their allocation, which can affect behaviour — but the outcome was a laboratory viral load measured by masked staff, which limits that bias.

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