The rebound that was counted

LATA randomised 476 virally suppressed adolescents aged 12 to under 20, from five clinics in Kenya, South Africa, Uganda and Zimbabwe, in an open-label assignment: 235 to cabotegravir–rilpivirine injections every 8 weeks, 241 to daily TLD tablets. Screening reached 560 people. The primary outcome was confirmed viral rebound by week 96 — the first of two consecutive viral loads of 50 copies per mL or higher — estimated by intent-to-treat adjusted Kaplan–Meier.[1]

There were 2 confirmed rebounds on injections and 15 on tablets: 0.9 per cent (95 per cent CI 0.0 to 2.2) versus 6.4 per cent (3.7 to 9.8). The difference was minus 5.5 points (99 per cent CI minus 10.3 to minus 1.5; p=0.0013). Of 476 randomised, 466 (98 per cent) entered that analysis. Move the threshold to 200 or 1000 copies per mL and superiority drops away; the signal lives in the 50-copy primary definition.[1]

When the control rate undershot the plan

The trial was built as non-inferiority: a fixed 10 per cent margin, two-sided alpha of 5 per cent, 90 per cent power, 460 people, and an assumed 11 per cent control event rate. The tablet arm landed at 6.4 per cent. The authors write that they used a SAFE framework so results stayed clinically readable if the control rate fell. Superiority was tested inside that margin and that threshold; adult cabotegravir–rilpivirine trials in the same class had stopped at non-inferiority.[1]

Participants were already on treatment for more than a year, virally suppressed, and without prior failure. Open label makes both the injection visit and tablet-taking visible; there is no blinding. Superiority is a drop in 50-copy rebound among people who passed that entry gate. An adolescent cohort starting treatment, or already failing, does not inherit the same margin.[1]

The next pulse

A stout repeat of the same protocol would need ages 12–19, prior suppression, 96 weeks, two consecutive 50 copies per mL reads, and a similar event rate on TLD. If the TLD arm climbs back toward 11 per cent, or the threshold moves to 200 copies, today's superiority sentence narrows. Cold chain, on-patent price and an 8-week injection roster still decide how the number travels into clinics in Kenya, South Africa, Uganda and Zimbabwe; those are not the trial's primary outcome.[1]