by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer
March 24, 2020
Long-acting formulations of the INSTI cabotegravir and the NNRTI rilpivirine have been studied in clinical trials for several years. Approval by the FDA is anticipated sometime in 2020. These phase 3 trials evaluated the efficacy of monthly injections with these 2 drugs in patients who had sustained viral suppression on oral therapy. The first study included 616 participants who had HIV-RNA levels of < 50 copies/mL for at least 6 months while on oral ART. They were randomized to continue oral therapy or switch to monthly IM injections of cabotegravir + rilpivirine. At week 48, 96% on oral therapy had viral loads < 50 copies/ml compared to 93% on long-acting IM treatment. There were 3 virologic failures in the long-acting therapy arm and 4 receiving oral therapy. In the second trial by Orkin and colleagues, 566 treatment naïve participants were first given 20 weeks of oral therapy which included dolutegravir-abacavir-lamivudine. Those who were undetectable (VL< 50 copies/mL) after 16 weeks were continued on oral therapy or switched to monthly IM injections of cabotegravir + rilpivirine. At week 48, approximately 94% in the long-acting IM therapy arm had viral loads of < 50 copies/mL compared to 93% who continued on oral therapy. Injection site reactions occurred in 81% of subject in the ATLAS trial and 86% in the FLAIR trial but only a small number (~2%) withdrew from the trials for this reason. In both studies, patient satisfaction was greater for the IM therapies as opposed to oral therapy, even in those who had received 12 monthly injections.
These two randomized trials provide strong evidence for ART given as a monthly injection. The FDA approval of Cabotegravir-Rilpivirine was anticipated at the end of 2019 year but was delayed due to scale-up manufacturing problems and not efficacy or safety concerns. In an accompanying editorial, Dr. Judith Currier expresses a generally favorable opinion regarding long-acting IM therapy for patients with HIV, but notes having patients come to busy HIV clinics for monthly injections will present some logistical challenges. New and encouraging data from FLAIR and ATLAS 2M trials were presented this month at CROI in Boston and will be discussed in a future Clinical Research Updates.
The author has no conflicts of interest to disclose.
View archived Clinical Research Update entries here.