ViiV Healthcare’s long-acting HIV treatment Cabenuva achieved superior viral suppression compared with daily oral antiretroviral therapy in people with detectable HIV, meeting the primary endpoint of the Phase 3b CROWN study.

The international trial evaluated whether adults and adolescents living with HIV-1 who had detectable virus despite previous treatment with daily oral antiretroviral therapy (ART) could begin long-acting cabotegravir and rilpivirine directly.

The finding could challenge the conventional treatment pathway, in which people generally need to achieve viral suppression on oral therapy before switching to long-acting treatment.

CROWN targets an unmet treatment challenge

CROWN enrolled approximately 326 adults and adolescents across 85 sites in eight countries.

The randomised, open-label study compared long-acting cabotegravir plus rilpivirine, administered six times a year, with daily oral ART. Participants entered the study with detectable HIV-1 virus and a history of daily oral treatment.

The trial was designed to address a gap in the evidence for people who struggle to achieve or maintain viral suppression while taking daily oral therapy.

ViiV said the CROWN population had no evidence of resistance to integrase inhibitors or non-nucleoside reverse transcriptase inhibitors, two classes of medicines relevant to the cabotegravir and rilpivirine regimen.

At six months, Cabenuva achieved superior viral suppression compared with daily oral therapy, meeting the study’s primary endpoint.

The company has not yet released the full efficacy and safety results, which are planned for presentation at an upcoming scientific meeting.

Long-acting treatment moves earlier in HIV care

The CROWN results build on findings from the LATITUDE study, which evaluated long-acting cabotegravir and rilpivirine in people with HIV who had already achieved viral suppression on oral ART but had a history of treatment adherence challenges.

LATITUDE found that switching to long-acting treatment was superior to continuing daily oral therapy in maintaining viral suppression. CROWN goes a step further by studying people who still have detectable virus when they enter the trial.

Jean van Wyk, chief medical officer at ViiV Healthcare, said: “People living with HIV who experience challenges achieving or maintaining viral suppression with daily oral therapy continue to face significant barriers to optimising care. The CROWN study was designed to address this important evidence gap.”

The findings therefore extend the evidence base for long-acting HIV treatment into a population that has historically presented greater challenges for achieving viral suppression.

Cabenuva use in people with detectable virus remains investigational

Cabenuva is currently approved for adults and adolescents living with HIV who are already virologically suppressed on a stable antiretroviral regimen, with no history of treatment failure and no known or suspected resistance to cabotegravir or rilpivirine.

Use of cabotegravir and rilpivirine in people with detectable HIV remains investigational and is not currently included in the approved indication.

The CROWN findings could therefore have implications for how long-acting treatment is considered for people who face persistent barriers to daily oral ART, although the full study results and subsequent regulatory assessment will be needed before any change in use can be considered.

The study adds to growing evidence around long-acting HIV treatment, including data from adolescents and real-world populations presented earlier this year.