ACTG Presents Study at CROI Demonstrating Efficacy of Long-Acting Injectable Treatment Among People Who Had Previously Been Unable to Maintain Viral Suppression on Daily Oral Medication

Mar 08, 2024

LOS ANGELES, March 06, 2024 (GLOBE NEWSWIRE) — ACTG, a global clinical trials network focused on HIV and other infectious diseases, today presented the oral abstract “Long-Acting Injectable CAB/RPV is Superior to Oral ART in PWH with Adherence Challenges: ACTG A5359” at the Conference on Retroviruses and Opportunistic Infections (CROI 2024), in Denver, Colorado. Today’s presentation includes the first data to demonstrate that long-acting cabotegravir and rilpivirine administered every four weeks had superior efficacy to daily oral antiretroviral treatment (ART) among people living with HIV who had previously been unable to maintain viral suppression while taking an oral daily regimen.

Approximately 34 percent of people living with HIV in the United States who take oral ART are unable to achieve viral suppression (which keeps their HIV from progressing to more advanced disease and prevents them from transmitting HIV to others). There are many reasons that may make it difficult for people living with HIV to take oral medication every day, including limited healthcare access, medication side effects, stigma, fear of disclosure, financial constraints, and mental health or substance use challenges, among others. ACTG designed A5359, also known as LATITUDE, to understand how a long-acting injectable ART regimen would work in people who had experienced challenges taking daily oral ART and were not able to maintain viral suppression.

“ACTG is thrilled to present this ground-breaking study at CROI,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “Long-acting injectables are an important treatment option and this study demonstrates that they can be successful in people who had previously been unable to maintain viral suppression, a group that was excluded from prior studies. These findings have the potential to dramatically improve the health and quality of life of these individuals.”

A5359 is a phase 3, prospective, randomized, open-label trial comparing monthly treatment with the long-acting injectable cabotegravir and rilpivirine to standard-of-care daily oral ART in people living with HIV who had historically been unable to maintain viral suppression. It is being conducted at 34 sites across the United States and Puerto Rico. Participants received incentives and support to adhere to their daily oral medication to first achieve viral suppression and if successful, they were randomized to either receive long-acting injectable treatment every four weeks or continue taking daily oral medication. On February 12, 2024, a planned interim review by an independent Data and Safety Monitoring Board (DSMB) recommended that the study stop randomizing participants and offer the long-acting injectable treatment to all eligible participants.

The interim data upon which the DSMB recommendations were made include 434 participants who were enrolled in the first step of the study (when all participants receive daily oral medication). The median age was 40 years old; 40 percent of participants were male, 64 percent were Black/African American, 17 percent were Hispanic, 5 percent were transgender, and 14 percent currently or previously used injection drugs. They had a median of 270/mm3 CD4+ cells and a median of 3.55 log10 c/mL HIV-1 RNA. Of the 294 eligible participants who were randomized in step 2 of the study, 146 received the long-acting injectable treatment and 148 continued to receive daily oral medication.

The long-acting injectable treatment was more effective than the daily oral medication at maintaining virologic suppression and avoiding treatment-related discontinuation. Twenty-eight participants receiving the long-acting injectable treatment experienced regimen failure (defined as virologic failure or treatment discontinuation), compared to 47 receiving daily oral medication. The DSMB concluded that there was strong evidence for superiority of the long-acting injectable treatment compared to the daily oral medication in this population, and therefore recommended stopping the randomized portion of the trial. The final analysis of the study efficacy results is ongoing.

The safety profile for cabotegravir and rilpivirine was consistent with prior studies and the regimen was generally well tolerated in this population. Adverse event rates were similar in both study arms. Three participants on long-acting injectables had severe injection site reactions and one discontinued with a mild injection site reaction. Two participants who experienced virologic failure in each arm had new resistance-associated mutations, including at least two new integrase inhibitor resistance-associated mutations in both participants receiving the long-acting injectable treatment.

“Until now, the population that was able to benefit from the availability of long-acting injectables has been limited to those with durable viral suppression on oral antiretrovirals and no history of failure on oral therapy,” said Protocol Chair Aadia Rana, M.D., University of Alabama at Birmingham. “The findings we shared today are an important step toward ultimately ensuring that people living with HIV facing challenges with adherence have access to a treatment option that meets their health needs, allowing them the potential to experience the health benefits of becoming virally suppressed.”

A5359 is led by Dr. Rana and Raphael J. Landovitz, M.D., University of California Los Angeles and Karen Tashima, M.D., Brown University (Vice Chairs). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., University of North Carolina (ACTG Vice-Chair). It is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. ViiV Healthcare and Johnson & Johnson provided study medications and were key partners in the study team.

About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.

Media Contact:
Rachel Reiss, ACTG