Final data from LATITUDE study show switch to long-acting injectable treatment reduced the risk of virological failure by nearly half for study participants through 48 weeks, compared to those continuing on daily oral therapy
ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer and Shionogi as shareholders, announced final data from the LATITUDE phase III trial, confirming its long-acting injectable treatment for HIV, Cabenuva (cabotegravir + rilpivirine), demonstrated superior efficacy in maintaining viral load suppression compared to daily oral therapy in individuals with a history of antiretroviral treatment (ART) adherence challenges.
The 48-week data were published in the New England Journal of Medicine, and followed a February 2024 recommendation from an independent Data and Safety Monitoring Board to halt randomisation in the study and invite all eligible study participants to take long-acting injectable cabotegravir + rilpivirine based on interim efficacy data.
Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare, said
The LATITUDE study adds to a robust body of evidence supporting the role of long-acting injectable cabotegravir + rilpivirine as a valuable treatment option for people living with HIV. This is the first randomised study confirming this regimen is superior to daily oral therapy in this population. As such, these findings have the potential to validate a long-acting approach for this additional group of patients and could make a significant difference to people living with HIV and our goal of ending the epidemic.
LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) is a phase III, randomised, open-label study which enrolled 453 participants who face challenges taking daily oral ART or who disengaged from HIV care. In the study, the median age was 40 years; 63% were Black/African American, 29% were female, 17% were Hispanic, and 14% reported either ongoing or prior injection drug use. Once enrolled, participants received adherence support including conditional economic incentives to achieve viral suppression while taking guideline-recommended daily oral ART. Researchers randomised 306 participants who were able to achieve viral suppression to either receive long-acting injectable (cabotegravir + rilpivirine) every four weeks (n=152) or continue taking daily oral ART (n=154).
The primary endpoint was a comparison of regimen failure between arms, defined as a combination of virologic failures (VF) and regimen discontinuation for any reason. The cumulative risk of regimen failure through 48 weeks of treatment was reduced by nearly half in the study: 22.8% for those who were switched to long-acting injectable cabotegravir + rilpivirine vs. 41.2% for people continuing on daily oral therapy (29/152 vs. 55/154, respectively).
Among participants receiving long-acting cabotegravir + rilpivirine in the trial, 29/152 (19%) experienced regimen failure, five (3%) of whom had VF and 24 (16%) had permanent treatment discontinuation as their first event. In the daily oral therapy arm, 55/154 (36%) experienced regimen failure, among whom 32 (21%) had VF as their first event and 23 (15%) had permanent treatment discontinuation.
Key additional endpoints at week 48 demonstrated the superiority of cabotegravir + rilpivirine vs. daily oral therapy:
| Endpoint |
Cumulative probability, long-acting injectable cabotegravir + rilpivirine (n=152) |
Cumulative probability, daily oral therapy (n=154) | Cumulative incidence difference (98.4% CI) |
| VF (events) | 6.8% (6) | 28.2% (34) | -21.4% (-33.5%, -9.3%) |
| Treatment-related failure* (events) | 8.9% (9) |
28.1% (34) |
-19.2% (-31.6%, -6.9%) |
| Permanent discontinuation of treatment (events) | 19.8% (26) | 28.2% (37) |
-8.4% (-21.3%, 4.5%) |
* Earliest occurrence of VF or premature treatment discontinuation due to treatment-related adverse events (AEs).
The rate of AEs was similar in both arms. The most common AE in the long-acting arm was injection site reactions (ISRs), with two participants discontinuing due to an ISR. Two confirmed VF in each arm (n=4 total) had new resistance associated mutations (RAMs), including two new integrase inhibitor RAMs in both long-acting arm participants.
Building on the LATITUDE study, ViiV Healthcare is conducting CROWN, a randomised study of long-acting cabotegravir + rilpivirine vs. daily oral therapy in people with adherence challenges and detectable virus. Unlike LATITUDE, which included a virologic suppression phase, CROWN evaluates the regimen directly in individuals who are not yet suppressed.
For more information, read the original press release.
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