Injectable CAB/RPV superior to oral ART in ART-nonadherent people with HIV

Treatment with cabotegravir and rilpivirine (CAB/RPV), a long-acting injectable antiretroviral therapy (ART), demonstrated superior efficacy in maintaining viral load suppression compared with oral standard of care (SoC) among people with HIV (PWH) who have difficulty adhering to ART, according to the ACTG A5359 LATITUDE* study presented at CROI 2024.

“Despite widely available and effective daily oral ART, some PWH are still unable to achieve and maintain viral suppression due to barriers to adherence … [and] long-acting injectable modalities could offer a directly-observed therapy alternative in this population and facilitate treatment success,” said Dr Aadia Rana from the University of Alabama in Birmingham, Alabama, US.

Thus, the researchers conducted the LATITUDE Step 2 study to analyse 294 patients with a history of suboptimal adherence (defined as those who have persistent HIV-1 RNA >200 copies/mL despite oral ART prescription for ≥6 months or were lost to clinical follow-up with ART nonadherence for ≥6 months).

During Step 1, all participants were given oral SoC ART for 24 weeks, and those who achieved viral suppression were enrolled in Step 2.

In Step 2, participants were randomized to receive monthly injections of long-acting CAB/RPV with or without oral lead-in (long-acting arm; n=146) or to continue daily oral SoC ART (SoC arm; n=148) for 52 weeks.

At week 52, only 24.1 percent of patients in the CAB/RPV arm experienced regimen failure, defined as the earliest occurrence of confirmed virologic failure or treatment discontinuation, while 38.5 percent were reported in the SoC arm. [CROI 2024, abstract 212]

As for secondary endpoints, fewer CAB/RPV-treated patients than SoC-treated patients had virologic failure (7.2 percent vs 25.4 percent) as well as treatment-related failure (9.6 percent vs 26.2 percent).

On the other hand, permanent treatment discontinuation was comparable between the long-acting and SoC arms (20.9 percent vs 24.9 percent).

“Although the primary endpoint did not meet the predefined stopping criteria for this interim analysis, key secondary endpoints of virologic failure and treatment-related failure met the stringent criteria, [favouring long-acting CAB/RPV regimen],” Rana noted. “On February 12, 2024, based on these findings, the Data and Safety Monitoring Board recommended halting randomization and that all eligible participants [should be offered] long-acting injectable therapy.”

In terms of safety, the rate of adverse events was similar in both arms.

Overall, 57 percent of patients in the CAB/RPV arm reported an injection site reaction (ISR), with pain, tenderness, and nodules being the most commonly reported reactions.

Moreover, three participants in the CAB/RPV-LA arm had grade ≥3 ISRs, whereas one patient discontinued treatment due to grade 1 ISR.

“Considering all endpoints together, [long-acting] injectable CAB/RPV demonstrated superiority when compared to daily oral SOC in PWH in the US who face barriers to adherence and have a prior history of virologic nonresponse or loss to clinical follow-up,” said Rana.

“These data support the use of long-acting injectable in this population and future clinical trials should assess the use of CAB/RPV injectable in actively viraemic patients,” she added.