ViiV Healthcare, the global HIV specialist company majority owned by GSK plc, with Pfizer and Shionogi as shareholders, reported that the 48-week data confirmed the superior efficacy of the long-acting regimen in maintaining viral suppression in this population.
The results follow a February 2024 recommendation from an independent Data and Safety Monitoring Board to halt further randomisation in the study and offer eligible participants the injectable regimen based on favourable interim efficacy findings.
LATITUDE (Long-Acting Therapy to Improve Treatment Success in Daily Life) enrolled 453 participants who either struggled with adherence to daily oral ART or had disengaged from HIV care. The median age of participants was 40 years; 63% were Black or African American, 29% were female, 17% were Hispanic, and 14% reported current or prior injection drug use.
Following enrolment, participants received adherence support, including conditional economic incentives, to achieve viral suppression while on guideline-recommended daily oral ART. A total of 306 participants who achieved viral suppression were then randomised to receive either long-acting injectable cabotegravir plus rilpivirine every four weeks (n=152) or to continue daily oral therapy (n=154).
The primary endpoint was regimen failure, defined as either confirmed virologic failure or permanent treatment discontinuation for any reason. Through 48 weeks, the cumulative risk of regimen failure was 22.8% in the long-acting arm compared with 41.2% in the daily oral therapy arm, representing nearly a 50% relative reduction in risk (29/152 vs. 55/154).
In the injectable arm, 29 participants (19%) experienced regimen failure, including five cases (3%) of virologic failure and 24 instances (16%) of permanent discontinuation as the first event. In the daily oral arm, 55 participants (36%) experienced regimen failure, with 32 cases (21%) of virologic failure and 23 discontinuations (15%).
Secondary analyses further supported the superiority of the injectable regimen. The cumulative probability of virologic failure was 6.8% in the long-acting group versus 28.2% in the daily oral group, a difference of -21.4 percentage points (98.4% confidence interval: -33.5% to -9.3%). Treatment-related failure occurred in 8.9% of participants in the injectable arm compared with 28.1% in the oral arm. Permanent discontinuation rates were 19.8% and 28.2%, respectively.
Adverse event rates were similar between groups. The most common adverse events in the long-acting arm were injection site reactions, with two participants discontinuing treatment due to such reactions. Four confirmed virologic failures across both groups were associated with new resistance-associated mutations, including two integrase inhibitor resistance mutations observed in participants receiving the injectable regimen.
LATITUDE was sponsored and funded by the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health, and conducted by the AIDS Clinical Trials Group. Additional support was provided by the National Institute of Mental Health, the National Institute on Drug Abuse, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, ViiV Healthcare and Johnson & Johnson.
Building on these findings, ViiV Healthcare is conducting the CROWN study, a separate randomised trial evaluating long-acting cabotegravir plus rilpivirine directly in individuals with detectable virus and adherence challenges. Unlike LATITUDE, which included a suppression phase prior to randomisation, CROWN is designed to assess the regimen’s effectiveness in people who have not yet achieved viral suppression.
The results from LATITUDE add to the growing body of evidence supporting long-acting injectable antiretroviral strategies as a potential alternative for individuals who face challenges with daily oral therapy, a population that continues to represent a critical gap in HIV treatment outcomes.
