ACTG Announces Publication of LATITUDE Findings in the New England Journal of Medicine

Study Confirms Long-Acting Treatment is Effective among People Living with HIV Who Experience Challenges Taking Daily Oral Treatment

CHAPEL HILL, N.C., Feb. 18, 2026 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the publication of “Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges” in the New England Journal of Medicine (NEJM). The publication reports that the long-acting injectable cabotegravir and rilpivirine was superior in preventing regimen failure among people living with HIV who have struggled with adherence to daily oral antiretroviral therapy (ART).

This publication reports on the LATITUDE study, also known as A5359, a phase 3 efficacy study of long-acting cabotegravir and rilpivirine, which is approved in the U.S. to be used as an injection every one or two months for people living with HIV with a consistent history of viral suppression. Because only an estimated 67% of people living with HIV in the U.S. who take oral ART maintain viral suppression, LATITUDE sought to determine whether this long-acting approach could achieve consistent virologic suppression among people who have difficulty taking oral ART. It is the first randomized study to do so.

“LATITUDE is a groundbreaking study, and these results enable us to significantly expand the population of individuals who will benefit from this long-acting treatment option,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “Since the U.S. Food and Drug Administration approved cabotegravir and rilpivirine in 2021, observational cohorts and case studies have suggested that these injectable agents may support viral suppression among people living with HIV who struggle with daily oral pills. Today’s publication validates the approach and will make a substantial difference in the experiences of these individuals living with HIV.”

LATITUDE enrolled 453 participants who demonstrated challenges taking daily oral ART or had disengaged from HIV care. The median age was 40 years; 63 percent were Black, 29 percent were female, 17 percent were Hispanic, and 14 percent reported either ongoing or prior injection drug use. Once enrolled, participants received adherence support including economic incentives to achieve viral suppression while taking daily oral ART. Researchers randomized 306 participants who were able to achieve viral suppression to either receive long-acting injectable ART every four weeks or continue taking standard-of-care daily oral ART. In February 2024, an independent Data and Safety Monitoring Board (DSMB) recommended halting randomization and inviting all eligible study participants to take long-acting ART based on interim efficacy data.

Today’s publication demonstrates that the risk of regimen failure (a measure that includes individuals experiencing unsuppressed HIV or discontinuing ART for any reason) through 48 weeks of treatment was almost twice as high in those continuing on oral ART compared to those who were switched to long-acting treatment (41.2 percent vs. 22.8 percent). Among the 152 participants receiving long-acting ART, 29 experienced regimen failure, five of whom had virologic failure and 24 had permanent treatment discontinuation as their first event. That compares to 55 of the 154 participants receiving daily ART who experienced regimen failure, among whom 32 had virologic failure as their first event and 23 had permanent treatment discontinuation.

Side effects were similar between study arms. The most common side effect in the long-acting arm was injection-site reactions (60 percent) with only two participants discontinuing as a result. There were four participants total (two in each arm) who acquired HIV resistance-associated mutations.

“The initial studies upon which the approval of long-acting cabotegravir and rilpivirine were based generally excluded people living with HIV who had viremia and who were not able to adhere to daily oral ART,” said study Chair Aadia Rana, M.D., University of Alabama at Birmingham. “People struggle to take daily HIV treatment for a variety of reasons, including social and structural barriers, side-effects, stigma, and competing priorities. It is vital we ensure that all individuals have access to the same robust set of HIV treatment options and the findings from LATITUDE are an important milestone toward that goal. The most important next steps will include ways to effectively implement these agents among these communities.”

LATITUDE is led by Dr. Rana and Raphael J. Landovitz, M.D., M.Sc., University of California Los Angeles and Karen Tashima, M.D., Brown University (Vice Chairs). ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice Chair). It is sponsored by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634, and received additional funding from UTHealth Houston McGovern School of Medicine. ViiV Healthcare and Johnson & Johnson provided medications for the study.

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:
Jenna Conley, ACTG
jenna@conleycommunications.net