Long-acting HIV injectable shows durable real-world efficacy

A nationwide cohort study in Spain has confirmed that the long-acting injectable regimen of cabotegravir plus rilpivirine effectively maintains viral suppression for the majority of people living with HIV who transition from daily oral therapy. Research reported that among 3,349 adults monitored across 53 clinical centers, 95.5% remained virologically suppressed after a median follow-up of 25.1 months.

The findings, published October 21, 2026, in Open Forum Infectious Diseases, offer a granular look at treatment persistence in routine care. While 89.0% of participants remained on the injectable regimen, 11.0% discontinued the therapy. Researchers noted that protocol-defined virologic failure was rare, affecting only 0.8% of the study population, with the majority of these instances occurring within the first year of switching to the injectable format.

Drug Resistance and Adverse Events Drive Treatment Failures

Data from the Spanish RELATIVITY cohort reveal that when virologic failure did occur, it was frequently associated with the development of drug resistance. Resistance to either integrase inhibitors or nonnucleoside reverse transcriptase inhibitors emerged in 19 of the 28 failure cases. In 11 of those patients, the virus developed resistance to both drug classes.

Discontinuations were largely driven by factors unrelated to the drug’s efficacy. Of the 370 participants who stopped the injectable regimen, 248 did so for nonvirologic reasons. Systemic adverse events accounted for 54 discontinuations, while injection-site reactions led 79 participants to leave the study. Despite these hurdles, patient adherence to the injection schedule remained high, with 99.3% of participants maintaining at least 90% compliance with their scheduled appointments.

Comparative Evidence from the United States

Recent data from the U.S.-based OPERA observational cohort provide additional context on the long-term use of cabotegravir plus rilpivirine, known commercially as Cabenuva. In an analysis covering nearly 7,000 individuals, ViiV Healthcare reported that 77% of “complete initiators”—those who finished their first two injections within a 67-day window—remained on the therapy with a median duration of 18 months. Among those with available follow-up data, 94% maintained viral suppression.

The OPERA study highlighted a diverse patient population, including 43% Black and 32% Hispanic/Latine participants, as well as a significant subset of individuals aged 50 and older. According to Dr. Ricky K. Hsu, lead author of the OPERA analysis and National Medical Director at the AIDS Healthcare Foundation, the real-world evidence reinforces the viability of long-acting options. The data offer vital, highly encouraging insights around treatment persistence with the long-acting therapy, showing that overall discontinuations were low and not commonly attributed to a lack of therapeutic efficacy or injection site pain, Hsu stated.

Guidance for Future Treatment Management

The authors of the Spanish study emphasize that while the injectable regimen is a strong maintenance option, it requires a structured approach to clinical oversight. They advocate for consistent monitoring of viral loads and swift action if a patient shows signs of rebound., of the Hospital Universitario de Burgos, led the research team in concluding that these 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.

Limitations noted in the Spanish study include its observational, uncontrolled design and the exclusion of specific populations, such as those who are pregnant, breastfeeding, or hepatitis B surface antigen-positive. The researchers also noted that the limited number of virologic failures made it difficult to pinpoint specific risk factors, and the study did not include routine drug level measurements to further characterize treatment outcomes.