Among people with HIV who switched to long-acting cabotegravir plus rilpivirine (CAB+RPV LA) while virologically suppressed, 94% had a last viral load below 50 copies/mL and 1% had confirmed virologic failure, according to five years of real-world data from the OPERA Cohort presented at IDWeek 2026.
Dr. Ricky K. Hsu, National Medical Director of Clinical Standards, Policy and Education at AIDS Healthcare Foundation and associate Professor of Medicine at NYU School of Medicine, presented the analysis.
Methodology
The investigators analyzed data from electronic health records from routine care at 101 clinics in 23 U.S. states and territories and included more than 172,000 people with HIV. They included ART-experienced adults who started CAB+RPV LA between Jan. 21, 2021, and Dec. 31, 2025, and who had not participated in the drug's clinical trials. The analysis included data with a cutoff date of Feb. 28, 2026.
Of 7,995 people who started the regimen, 6,955 (87%) had a viral load below 50 copies/mL at initiation. Another 898 (11%) did not, and 142 had no baseline viral load in the prior 12 months. The analysis centered on the suppressed group, in which 86% were male, 43% were Black, 32% were Hispanic, 23% were 50 or older and 5% reported ever injecting drugs. Median CD4 count was 712 cells/µL, and 30% had a BMI of 30 kg/m2 or higher. Participants had spent a median of 21 months on their prior regimen, which was integrase inhibitor-based in 79%.
The main analyses included 6,362 people with complete initiation (92%), whose first two injections were no more than 67 days apart. Discontinuation was defined as no injections for more than 127 days, and confirmed virologic failure was defined as two consecutive viral loads of 200 copies/mL or higher, or one viral load of 200 copies/mL or higher followed by discontinuation within 4 months.
Virologic Outcomes, Adherence and Persistence
Among 6,058 complete initiators with follow-up viral loads, 5,700 (94%) had a last viral load below 50 copies/mL during their first uninterrupted CAB+RPV LA use. All viral loads stayed below 50 in 4,891 (81%), and 68 (1%) met the failure definition.
Among 5,713 complete initiators with baseline viral load < 50 copies/mL and who had at least one maintenance injection, 3,119 (55%) received every injection on time. The other 2,594 (45%) had at least one late injection.
At study end, 4,879 complete initiators (77%) were still receiving CAB+RPV LA, with a median of 18 cumulative months on treatment. Of the 6,362 complete initiators with baseline viral load < 50 copies/mL, 4,458 (70%) never discontinued, 421 (7%) discontinued and resumed, and 1,483 (23%) discontinued.
“Real-world studies are meant to complement these studies because in the real-world setting, patients are extremely diverse, and they bring real-life challenges that may affect the success and outcomes of drug treatment,” Hsu said in an interview, referring to randomized trials. “This OPERA real-world study should give providers reassurance of the durability and efficacy of the real-world use of CAB+RPV LA, as nearly 7,000 patients over 5 years of follow-up illustrated that the efficacy rates were nearly identical to the pivotal randomized clinical studies that led to the drug's approval.”
Reasons for Discontinuation
Providers were surveyed about 213 patients who discontinued. Adherence issues were cited for 59 patients (28%), loss to care for 51 (24%), preference for another regimen for 31 (15%) and cost for 28 (13%). Unintended effects, which included drug interactions, toxicity, lab abnormalities, non-injection-site events and hypersensitivity, were cited for 20 (9%). Injection-site events, described as pain or nodules, accounted for 14 (7%), as did virologic effectiveness concerns such as blips, rebound or failure.
Persistence was not analyzed by subgroup, but Hsu said that an earlier analysis presented in Glasgow showed no difference in confirmed virologic failure among Black patients, Hispanic patients or those older than 50. Because discontinuation was part of the failure definition, he said he assumes persistence was similar.
Hsu said the 11% who started CAB+RPV LA with viremia warrants attention. Many providers use the regimen off label in viremic patients who struggle with oral medications, he said. He cited the LATITUDE and CROWN studies and an earlier 4-year OPERA analysis as supporting that use, potentially contributing to evidence for a label change. He added that the regimen is being studied for dosing every 4 months.
The study is sponsored by ViiV Healthcare. Hsu reported financial relationships with Epividian (advisor/consultant, board member), Gilead (grant/research support), Merck (honoraria), and ViiV (advisor/consultant, grant/research support, honoraria).
