Promising New Treatment for Persons Living with HIV: Clinical Trial of Long-Acting, Injectable Antiretroviral Therapy Reveals Positive Findings

In clinical trial findings presented in early March at the 2024 Conference on Retroviruses and Opportunistic Infections, long-acting, injectable antiretroviral therapy suppressed HIV replication better than oral ART in patients with HIV who have struggled taking daily oral regimens.

Aadia Rana, M.D., professor of medicine in the Division of Infectious Diseases at the University of Alabama at Birmingham, senior scientist with the UAB Center for AIDS Research and study chair for the National Institutes of Health-funded Long-Acting Therapy to Improve Treatment SUccess in Daily LifE, or LATITUDE, study, explained that at a planned review of the study data by an independent safety monitoring board conducted last month, the monthly cabotegravir and rilpivirine injections were found to be more effective in suppressing HIV compared to daily pills. The board recommended halting randomization and offering all participants long-acting injectable therapy.

According to the Centers for Disease Control and Prevention, it is estimated that up to a quarter of people prescribed oral ART stop taking the medication at some point, often due to factors including mental health or substance use challenges, competing responsibilities and financial constraints, and stigma. While transformable in the treatment of HIV, ensuring that patients have access to an ART regimen that is easy to adhere, ultimately limiting transmission of HIV to others and providing suppression for those infected. Alabama is one of seven priority states in the National Ending the HIV Epidemic Initiative in the United States, a bold initiative that aims to end the HIV epidemic in the United States by 2030.

“This study is critically important because it shows that long-acting injectable HIV medications can provide substantial benefit to a broader population than those covered by the current regulatory approvals,” Rana said. “If guidelines were to recommend such broader use, it would be expected to have a large impact on rates of new HIV infections, as most infections are transmitted by persons with HIV who are aware of their diagnosis but do not have suppressed virus. This study is a clear demonstration that large, randomized treatment trials in a population with challenges to adherence can be successfully done, and it is a call to action to include these historically ‘hard to reach’ populations earlier in the process of drug development, particularly in the long-acting therapeutic space.”

The LATITUDE study, implemented through ACTG — a global NIH-funded clinical trials network focused on HIV and other infectious diseases — started enrolling participants in March 2019. LATITUDE compared monthly injectable HIV medications cabotegravir and rilpivirine to daily oral tablets in people with HIV who had a history of challenges with taking their daily medications.

Participants in the study received comprehensive adherence support including conditional financial incentives to achieve viral suppression on oral therapy first. Those who were successful in achieving viral suppression were then randomized, to monthly injections or to continue on their daily oral pills for approximately one year. The Alabama Clinical Research Site of the ACTG, based at UAB, was one of the highest enrollers in the study.

“Our hope is that this study will expand HIV treatment guidelines for long-acting injectable treatment to include people with a history of non-adherence and influence the payor decisions,” Rana said. “Our next challenge is to continue implementation of this strategy in those who would benefit the most.”