NEW YORK (Reuters Health) – Cabotegravir plus rilpivirine given by injection every eight weeks appeared to be a promising new therapeutic option for people living with HIV at the 48-week mark in the ATLAS-2M trial.
The drug, Vocabria, was approved on Tuesday for use in Europe.
The study results are “great news for the field of HIV,” Dr. Edgar Overton of the University of Alabama at Birmingham told Reuters Health by email. “Once approved, we will have an alternative to oral therapy for people living with HIV. I look forward to collaborating on additional studies to expand the use of these long-acting injectable therapies to more patients.”
ATLAS-2M is an ongoing, randomized, multicenter (13 countries), open-label, phase-3b non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy given intramuscularly every eight weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every four weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults.
The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies/mL or more.
A total of 1,045 participants (median age, 42; 27% female at birth; 73% white) were randomized to receive therapy every eight or four weeks, including 391 (37%) who transitioned from every four weeks in the phase-3 ATLAS study.
With respect to the primary endpoint, giving the injectable treatment every eight weeks (2%) was non-inferior to dosing every four weeks (1%), with an adjusted treatment difference of 0.8.
Virologic failures, defined as two sequential measures of at least 200 copies/mL, occurred in eight individuals (2%) in the every-eight-weeks group and two (<1%) in the every-four-weeks group, the researchers report in The Lancet.
The safety profile was similar between the dosing groups; 81% experienced adverse events (excluding injection-site reactions); no treatment-related deaths occurred.
Injection-site reactions, particularly pain, were the most common adverse events, affecting three-fourths of the participants. Overall, participants preferred the eight-week regimen.
Three HIV experts not involved in the study welcomed the findings.
“While most people with HIV around the world successfully take their medicines every day, being able to switch from a daily pill to an injection six times a year would be truly life-changing,” Dr. Annette Sohn of amfAR, The Foundation for AIDS Research, told Reuters Health by email.
“The majority of participants in the ATLAS-2M study were over the age of 40,” she noted. “Populations who could substantially benefit from less-frequent HIV treatment are adolescents and young adults struggling with adherence. However, because of how long these drugs stay in the body, there is a greater risk of drug resistance should they miss their injection schedule.”
“Delivering the 3 ml injections could be challenging,” she added. “Three-fourths of the ATLAS-2M participants had injection-site reactions, which, although mild, could complicate adherence in real-world contexts.”
Dr. Barbara Gripshover, medical director of the John T. Carey Special Immunology Unit at University Hospitals Cleveland Medical Center, in Ohio, said, “For patients who prefer long-acting injectable ART (antiretroviral therapy) to a daily pill, this will present a nice new option.”
“Currently, this regimen has only been studied in persons already virally suppressed on oral ART, to avoid the chance of developing resistance to the medication in the setting of ongoing viral replication,” she told Reuters Health by email. “However, (this treatment) may be especially promising in persons unable to take daily pills who are not virally suppressed. Studies are ongoing to help support patients with adherence to oral medication, in the hope of then transitioning them to long-acting injectable ART.”
Dr. Cathy Creticos, director of Infectious Diseases at Howard Brown Health in Chicago, said, “The study provides encouraging data and is needed to allow patients living with HIV to have additional options that can help them adhere to treatment and remain healthy.”
“Howard Brown Health is participating in a study looking at every-eight-weeks treatment with injectable cabotegravir/rilpivirine in patients who have been stable and suppressed on a particular oral HIV treatment regimen,” she told Reuters Health by email, “and this will help further understand the efficacy and safety of this regimen, as well as identify patients for whom this may be a successful treatment.”
The study was funded by ViiV Healthcare and Janssen. Many coauthors are employees of one or the other company. Dr. Overton and several other coauthors have received funds from the company.
SOURCE: https://bit.ly/2KmkZhT and https://bit.ly/2Kv5LqN The Lancet, online December 9, 2020.