Real-World HIV Study Allays Doubts About Long-Acting ART Injectables

— Virologic suppression remained the norm after a switch from oral ART

WASHINGTON -- Long-acting injectable antiretroviral therapy (ART) maintained virologic suppression for HIV patients, with virologic failure rarely observed over more than 5 years, real-world data showed.

Among OPERA cohort participants who switched from oral ART to long-acting cabotegravir/rilpivirine (Cabenuva), 94% who received at least two injections had undetectable levels of HIV at their last virologic load test, and 81% of these patients remained at or below undetectable levels of HIV at every virologic load test, reported Ricky Hsu, MD, of NYU Langone Medical Center in New York City, at the IDWeekopens in a new tab or window annual meeting.

Only 1% experienced confirmed virologic failure, defined as two consecutive viral loads ≥200 copies/mL or one viral load ≥200 copies/mL followed by discontinuation of long-acting cabotegravir/rilpivirine.

Our data show that long-acting injectables were "highly efficacious in the real world," Hsu said during a press briefing ahead of the meeting. These results could "help increase provider buy-in with the real-world demonstration of the efficacy, persistence, and continued patient interest in long-acting injectable therapy, which really mirrors that of the randomized clinical studies."

Long-acting cabotegravir/rilpivirine remains the only complete injectable ART that is a recognized alternative to daily oral therapy. It was FDA approved in 2021opens in a new tab or window, initially as a monthly injection before it was expanded for use every 2 months, for virologically suppressed patients on a stable ART regimen with no history of treatment failureopens in a new tab or window and with no known or suspected resistance to either cabotegravir or rilpivirine.

"This long-acting injectable now has been available for over 5 years, but when you look at what's actually prescribed ... you see that it constitutes only about 5% of all the HIV prescriptions that are out there," Hsu noted. "So, I think there's a real importance to also gain provider buy-in into long-acting injectable treatmentopens in a new tab or window."

This study may ease concerns that injection-site reactions and virologic failureopens in a new tab or window would be major barriers to the therapy in the real world, he added.

Among patients who stopped their injections in OPERA, their providers said in a survey that the most common reasons were nonadherence to injection visits, loss to care, and desire to switch to oral ART. "What we found was the reasons for discontinuations were very infrequently due to injection-site reactions or lack of efficacy," Hsu said. "There were more due to logistical challenges such as insurance or patients being lost for follow-up."

There is mounting evidenceopens in a new tab or window for expanding long-acting injectable ART to populations in need -- including patients who continue to be viremic and those who have difficulty sticking to or taking oral medicinesopens in a new tab or window.

OPERA is a large longitudinal healthcare database representing about 14% of HIV patients across the U.S.

Hsu and colleagues identified a cohort of 7,995 ART-experienced, virologically suppressed (viral load <50 copies/mL) adults who switched to long-acting cabotegravir/rilpivirine from January 2021 to December 2025.

Median age was 37, 86% were men, 43% were Black, and 32% were Hispanic. Just under 80% had a CD4 count of at least 500 cells/µL, and median time on a prior regimen was 21 months. An estimated 87% were virologically suppressed at initiation.

Of the complete initiators -- 6,362 people who had their first two injections up to 67 days apart -- 77% stayed on the injectable therapy at study end, interruptions or not, and their median duration on these cabotegravir/rilpivirine injections reached 18 months.

"By adding real-world data that reflects everyday challenges facing patients in accessing care to the evidence-base, these findings further validate randomized clinical trials that show cabotegravir plus rilpivirine as an effective and valuable option for those living with HIV," Hsu said in a press release.