April 21, 2021
Reviewed by Lauren Richey, MD, MPH, FIDSA
Given the burden of daily pills and the need for lifelong medications, there is interest in simpler treatment regimens for people with HIV. Cabotegravir, a structural analog to dolutegravir, and rilpivirine, a non-nucleoside reverse transcriptase inhibitor, are currently formulated and approved by the Food and Drug Administration (FDA) as long-acting injectable agents with dosing every 4 months. With the present requirement of two separate gluteal injections, limited distribution to only specific pharmacies, and an oral lead-in requirement, the current treatment setting is within a clinic. Dosing every 4 weeks makes this regimen difficult logistically to implement and will limit its use. ATLAS-2M, a randomized, open-label, 3B, non-inferiority study, was designed to compare a higher dose of cabotegravir and rilpivirine intramuscularly every 8 weeks versus the currently approved every 4 weeks dosing. Results were reported in Lancet.
Participants were people with HIV who were virally suppressed on either a first or second standard-of-care regimen without a history of virologic failure or known mutations to the study drugs. Participants were randomized, with over 500 people in both the 4- and 8-week dosing groups. At 48 weeks, nine (2%) of the 8-week regimen and five (1%) of the 4-week regimen had viral loads over 49 copies per mL. These failures were driven by both archived and newly acquired mutations. For the 8-week regimen, 94% were undetectable (copies per mL < 50) as were 93% of the 4-week dosing regimen. Both outcomes were non-inferior. Discontinuation and adverse events were similar.
Eight-week dosing is more logistically feasible in the clinic setting and was shown to be safe and efficacious in this study. More data is needed on whether this regimen is as efficacious in patients with a history of virologic failure and poor retention. FDA provides guidance on how to address missed doses for the currently approved 4-week dosing (clinical assessment and then regular dosing if ≤ 2 months since last injection, higher loading dose if > 2 months). However, information on dosing after missed injections with 8-week dosing will be needed.