Switch from oral to injectable ART maintains viral suppression, highly acceptable to teens

In adolescents with well-controlled HIV, switching from an oral antiretroviral therapy (ART) regimen to the long-acting injectable cabotegravir plus rilpivirine combination appears to be not only safe and efficacious in maintaining viral suppression but also strongly favoured, according to the end-of-study data from the phase I/II IMPAACT 2017 study.

Through week 96, virologic suppression (HIV-1 RNA <50 copies/mL) was maintained in 94.4 percent of participants, and there was no confirmed virologic failure (two consecutive HIV-1 RNA ≥200 copies/mL), reported lead investigator Dr Aditya Gaur from St Jude Children’s Research Hospital in Memphis, Tennessee, US. [CROI 2026, abstract 155]

“There were viral blips during the injection phase, with 11 participants having at least one viral load of >50 copies/mL, two of whom had >200 copies/mL, but none led to virologic failure,” Gaur said.

Grade 3 or higher adverse events (AEs) occurred in 31 percent of participants. The most common was elevated creatine phosphokinase levels in blood (12.5 percent).

Fewer than half (42 percent) of the participants experienced drug-related AEs, with injection-site reactions (ISRs) accounting for the majority of these AEs. A total of 346 ISRs were reported by 37 percent of participants, and most were grade 1 injection site pain that lasted no more than 7 days.

Two participants had grade 3 drug-related AEs, an abscess in one and concurrent pain and abscess in the other. Nine possible postinjection reactions were documented, and one of these was a grade 4 anaphylaxis that led to drug discontinuation. This incident, according to Gaur, “provides a practical reminder to clinicians to differentiate postinjection reactions from anaphylaxis or allergic reactions.”

In terms of acceptance and tolerability, more than 97 percent of participants expressed preference for the long-acting injections than daily oral treatment. This was despite the variable reporting of pain, noted Gaur.

Over 96 weeks, the pharmacokinetic profile of the long-acting injectable cabotegravir plus rilpivirine was comparable to that of adults receiving the same regimen in the ATLAS-2M phase IIIb study. Cabotegravir reached a steady state, while rilpivirine was still accumulating at 96 weeks but well within the safety margins for the drug, according to Gaur.

Taken together, these data help inform not only regulatory submissions but also counselling about what to expect when you’re putting the next adolescent on this treatment, he concluded.

IMPAACT 2017 was conducted at 18 centres across Botswana, South Africa, Thailand, Uganda, and US. The analysis included 144 virologically suppressed adolescents with a body weight of ≥35 kg. These participants had been switched from 4 weeks of daily oral cabotegravir–rilpivirine combination to long-acting injectable cabotegravir 600 mg plus rilpivirine 900 mg, administered as an intramuscular injection at weeks 4 and 8, and then every 8 weeks for 96 weeks, with an option to continue for 48 more weeks.

The median age of the participants was 15 years, and 51 percent were female, and 74 percent were Black. The median BMI was 19.5 kg/m², and 92 percent had vertically acquired infection.

Study retention was high, with a total of 137 participants (95 percent) completing week 96, with median exposure of 137.5 weeks. These participants received ≥13 injections.