Cabenuva proves effective in practice

Adherence to daily antiretroviral therapy (ART) can be challenging for some people with HIV (PWH). Therefore, finding an effective alternative to daily ART is a priority for researchers and clinicians who treat HIV. Three posters presented at CROI 2025, in San Francisco, indicate that the use of injectable long-acting cabotegravir plus rilpivirine (LA-CAB+RPV; Cabenuva, ViiV Healthcare), is an effective option because it is administered monthly or bimonthly.

Continuing Treatment, Even With High BMI

The OPERA Cohort, a group of PWH treated with LA-CAB+RPV during the first three years of its availability, looked at people who were treatment experienced and virally suppressed (viral load [VL], <50 copies/mL [c/mL]) (poster 674).

“Individuals receiving LA-CAB+RPV were able to use this medicine for a year or more, they were able to take it according to the schedule, and they kept their viral load very low,” explained study author Michael Sension, MD, an infectious disease specialist at CAN Community Health, in Fort Lauderdale, Fla.

Among the 2,858 people included in the research, 2,626 (92%) completed initiation. Median follow-up among participants who completed initiation was 11 months and 2,182 (83%) were on LA-CAB+RPV at time of analysis; 83% received their second injection on-time, and maintenance injections were on-time in 60% of the 2,401 receiving maintenance injections.

Most study participants (94.8%) maintained virologic suppression at their final viral load measurements, and 83% had no virologic blips [all VLs <50 c/mL]). Virologic suppression was seen in 954/1,015 (94%), 511/538 (95%), and 85/89 (96%) of participants during the six, 12 and 24-month VL measurements. Confirmed virologic failure (CVF) was defined as two VLs at least 200 c/mL or one VL at least 200 c/mL and discontinuation. CVF was observed in 32 (1%) participants, with 17 CVFs occurring within the first six months of treatment. None of the factors evaluated as predictors of CVF reached statistical significance.

Neither virologic suppression (all VLs: 83% vs. 84%; last VL: 95% vs. 94%) nor CVF (1% vs. 1%) significantly differed by body mass index (BMI) (<30 kg/m² vs. =30 kg/m²), the study found.

Dr. Sension explained that in early clinical trials of LA-CAB+RPV, high BMI (=30 kg/m²) appeared to be associated with virologic failure. “This study shows that in clinical practice providers are able to mitigate that risk of high BMI either through careful placement of the injections or use of longer needles or both,” continued Dr. Sension—an important consideration because many in the United States have a high BMI.

For many, “taking pills every day is [an unwanted] daily reminder of their HIV and for these individuals a long-acting injectable medication [allows them to] avoid this daily reminder,” while effectively suppressing their disease, he said, adding he plans to continue evaluating predictors of CVF in patients on LA-CAB+RPV by analyzing larger sample sizes.

Success in Women

Another part of the OPERA cohort looked at the efficacy of LA-CAB+RPV among virologically suppressed women (poster 676). “The key findings of our research were that women were able to receive the injections on time, able to take LA-CAB+RPV for a year, and had few failures,” explained researcher Jessica A. Altamirano, MD, an infectious disease specialist at CAN Community Health, in Miami Gardens, Fla.

Establishing the efficacy of LA-CAB+RPV in women is important, according to Dr. Altamirano, because “in the U.S., women make up about 20% of the people living with HIV, [but] their outcomes and experiences tend to be overshadowed and underresearched. However, their challenges are unique, and their outcomes could be quite different” if more research was conducted with women.

A total of 415 women were included in the study, and 381 (92%) completed initiation, 293 [77%] on bimonthly injections and 75 [20%] on monthly injections. They were followed for a median of 12.4 months. At study end, 297 (78%) were on LA-CAB+RPV. Among 340 women (89%) with known dosing schedules and at least one maintenance injection, 148 (43%) received all maintenance injections on time, while 125 (37%) had at least one delayed maintenance injection and 42 (12%) had at least one missed maintenance injection. Among 372 women (98%) with at least one follow-up VL measurement, most maintained suppression (94% at last VL, 82% at all VLs) and seven (2%) experienced CVF. Like Dr. Sension’s study, Dr. Altamirano’s research was limited by a lack of data on variables correlated with CVF and dropout.

However, the study shed light on the fact that, compared with men using LA-CAB+RPV in the OPERA cohort, women were slightly older, more likely to be Black, and less likely to be of Hispanic ethnicity, Dr. Altamirano noted. Most importantly, the study confirmed that LA-CAB+RPV is effective for treating women with HIV in the real world.

Questions Remain on Discontinuation

Results supporting the efficacy of LA-CAB+RPV in practice from the two studies of the OPERA cohort were reinforced by a third poster presented at CROI, which analyzed the use of LA-CAB+RPV among 1,198 ART-experienced adults with HIV in the Trio Cohort (abstract 675).

“The performance of LA-CAB+RPV in clinical practice is looking very similar to how it looks in the clinical trials. The number of people who developed resistance [in the Trio Cohort] was very small, and that’s the biggest concern,” explained study author Paul Sax, MD, of Brigham and Women’s Hospital, in Boston.

After the first injection, and a median follow-up time of 12 months, 923 (77%) study participants remained on LA-CAB+RPV. Among all LA-CAB+RPV initiators, 928 (77%) had at least one follow-up VL; among these, 882 (95%) had a VL lower than 50 c/mL. CVF was observed in 15 (1.6%) individuals, of whom, eight (53%) had longer than two months follow-up on a subsequent regimen, with re-suppression observed in six individuals (75%). No statistically significant factor leading to CVF was identified.

Among the people assessed in the Trio Cohort, there were 275 PWH who discontinued LA-CAB+RPV, but 24 (9%) re-initiated treatment. As in the OPERA trials, exact reasons for discontinuation were unknown.

However, high rates of discontinuation is an area in which “many real-world studies differ from the clinical trials. It looks like about 15% to 20% of people just sort of don’t want to continue with injections,” Dr. Sax said.

He noted that his clinical experience led him to believe that this was due to injection-site reactions, the hassle of coming to the medical center every two months, or a combination of the two reasons.

He concluded that the significance of real-world trials of LA CAB+RPV is making clear the difference between clinical trial populations, who are often highly motivated and given incentives to stay in a study, and the general population who might be more likely to stop a treatment for a number of reasons.

By Myles Starr