Long-acting injectable cabotegravir plus rilpivirine maintained viral suppression in 95.5% of patients living with HIV in a large-scale Spanish cohort study. Published in Open Forum Infectious Diseases on October 21, 2026, the findings indicate that this bimonthly regimen serves as a durable maintenance option for people with HIV who have transitioned from suppressive oral antiretroviral therapy.
The RELATIVITY cohort study tracked 3,349 adults across 53 centers in Spain, with a median follow-up period of 25.1 months. Researchers found that 89.0% of participants remained on the injectable regimen, while 11.0% discontinued the therapy. Among those who stopped the treatment, the majority of discontinuations—7.4% of the total cohort—were attributed to nonvirologic factors, while injection-site reactions and systemic adverse events accounted for 2.4% and 1.6% of discontinuations, respectively. A total of 99.3% of evaluable participants maintained injection-timing adherence of 90% or higher.
Participants Develop Drug Resistance After Early Treatment Failure
Protocol-defined virologic failure was observed in 28 participants, representing 0.8% of the study population. The majority of these failures occurred within the first year of treatment, with 20 of the 28 cases occurring within that 12-month window. Among the cases of failure, 67.9% of participants developed new resistance to either integrase inhibitors or nonnucleoside reverse transcriptase inhibitors, with 39.3% showing resistance to both drug classes.
The study authors emphasized the necessity of early clinical monitoring and prompt confirmation of viral rebound. They noted that their findings support CAB + RPV LA as a durable maintenance option for appropriately selected PWH and emphasize early monitoring, prompt confirmation of rebound, resistance testing, and individualized rescue therapy.
Comparative Data from the OPERA Cohort
Among 6,058 complete initiators, 94% achieved a final viral load measurement of less than 50 copies/mL, while 1% experienced confirmed virologic failure. Dr. Ricky K. Hsu, lead study author and National Medical Director at the AIDS Healthcare Foundation, stated: By evaluating nearly 7,000 individuals in routine clinical care, this analysis gathered over the five-year OPERA study adds to and strengthens the clinical and real-world evidence base for long-acting cabotegravir and rilpivirine.
He added: These are important insights for healthcare providers as they consider the full breadth of treatment options available to their patients.
Limitations of the Real-World Data
While the study provides significant evidence for the effectiveness of the injectable regimen in a real-world setting, it carries inherent limitations. As an observational and uncontrolled study, clinicians selected the treatments rather than following a randomized protocol. The researchers excluded specific populations, including those who were pregnant, breastfeeding, or hepatitis B surface antigen-positive. Three authors disclosed receiving lecture fees, speaker honoraria, or support for attending meetings from ViiV, Johnson & Johnson, and Gilead, though these were noted as unrelated to the study.
Due to the low number of virologic failures, the team was unable to definitively identify specific risk factors associated with treatment failure. The study did not collect drug level measurements, and many participants lacked historical resistance test results, leaving questions regarding the exact drivers of the observed resistance patterns in the small subset of patients who experienced viral rebound.
