Cabotegravir Plus Rilpivirine Holds Up in 5 Years of Real-World Data

Of 6362 people with HIV who completed initiation of long-acting cabotegravir plus rilpivirine (CAB + RPV LA; Cabenuva; ViiV Healthcare) in US care, 77% remained on therapy at a median of 18 months.^1,2 The 5-year OPERA cohort data were presented at IDWeek 2026, held October 21-24 in Washington, DC.¹ Among 6058 complete initiators with a follow-up viral load, 94% had a last viral load below 50 copies/mL, and 1% experienced confirmed virologic failure.^1,2

The analysis included 6955 virologically suppressed adults who switched from daily oral antiretroviral therapy (ART) to CAB + RPV LA between January 2021 and December 2025, with follow-up through February 2026.² Jean van Wyk, MBChB, MFPM, chief medical officer, ViiV Healthcare, said the outcomes are very consistent with what the regimen showed in clinical trials, including retention among people who completed their initiation injections.

Black adults made up 43% of participants and Hispanic/Latine adults 32%, while 23% were aged 50 years or older and 30% had a body mass index of 30 or higher.² Overall, 81% of complete initiators with follow-up viral load data maintained suppression below 50 copies/mL at every visit.² Discontinuation was confirmed for 213 individuals, most often because of adherence issues (28%), loss to care (24%), or preference for another regimen (15%).²

Van Wyk said the 5-year OPERA analysis also covered more than 3000 people using long-acting cabotegravir for HIV preexposure prophylaxis (PrEP), among whom about 0.2% acquired HIV.

“It’s very reassuring that in the real world, these long-acting injectable medications are behaving consistently with what we’ve seen in clinical trials,” said van Wyk.

Starting Long-Acting Therapy in People With Viremia

CAB + RPV LA is approved only for people who are virologically suppressed on a stable regimen.³ In October 2026, ViiV announced the phase 3b CROWN trial (NCT06694805) met its primary end point, with superior viral suppression at 6 months vs daily oral ART in people with detectable virus at study entry.³ Full results have not been released and are planned for an upcoming scientific meeting.³

CROWN enrolled about 326 adults and adolescents with HIV-1 RNA between 1000 and 100,000 copies/mL and a documented lapse in oral ART of at least 30 consecutive days.^3,4 It builds on the phase 3 LATITUDE trial, in which CAB + RPV LA cut virologic failure to 6.8% vs 28.2% with oral ART among participants who first achieved suppression on oral therapy.³

Van Wyk said viremia in treatment-experienced patients is usually driven by nonadherence, which shaped the design of starting injections directly instead of suppressing on oral therapy first.

“If you already can’t take an oral medication every day to stay suppressed, logically it would be better if you could go straight to a long-acting injectable rather than suppress first on orals,” said van Wyk.

Van Wyk noted about 10% of people starting CAB + RPV LA in the OPERA database are already viremic at initiation, an off-label use. In that setting, he advised confirming no resistance to cabotegravir or rilpivirine before starting therapy and monitoring patients closely. ViiV plans to share the CROWN data with health authorities for regulatory review.³

Reaching people who have fallen out of care may also require new support structures. Van Wyk pointed to mobile clinics in the community and nurse-administered injections at home for patients who prefer them, and said ViiV is planning implementation work on barriers to care and linkage back into care.

References

1. Hsu RK, Sension MG, Fusco JS, et al. High suppression and rare virologic failure with long-acting cabotegravir + rilpivirine: real world evidence over five years from the OPERA cohort. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.

2. Five years of U.S. real-world evidence reinforce the durable effectiveness and long-term persistence of ViiV Healthcare's Cabenuva. News release. ViiV Healthcare. October 21, 2026. Accessed October 29, 2026. https://www.biospace.com/press-releases/five-years-of-u-s-real-world-evidence-reinforce-the-durable-effectiveness-and-long-term-persistence-of-viiv-healthcares-cabenuva

3. Long-acting cabotegravir/rilpivirine superior to daily oral ART for HIV. Contagion. October 6, 2026. Accessed October 29, 2026. https://www.contagionlive.com/view/long-acting-cabotegravir-rilpivirine-superior-to-daily-oral-art-for-hiv

4. A study to evaluate the effectiveness of long-acting (LA) cabotegravir (CAB) + rilpivirine (RPV) LA when given to participants with detectable HIV-1 (CROWN). ClinicalTrials.gov identifier: NCT06694805. Updated July 2026. Accessed October 29, 2026. https://clinicaltrials.gov/study/NCT06694805