Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection

SPS commentary:

This is one of two international, phase 3, randomized trials reported in the New England Journal Medicine reporting that 48-week outcomes among people living with HIV who received antiretroviral therapy (ART) as monthly injections of long-acting suspensions of the integrase strand-transfer inhibitor cabotegravir and the nonnucleoside reverse-transcriptase inhibitor rilpivirine were non inferior to continued daily oral treatment I terms of HIV-1 suppression and participants in both trials clearly preferred monthly injections over daily oral therapy.

 

An editorial notes that when approved by regulators, this major advance in treating HIV infection will provide a new option for a select group of patients who currently have viral suppression while taking ART and represents the first step toward making less-frequent dosing of ART a reality. It adds however that the overall effect this new treatment approach has on the HIV epidemic will depend on the ability to address a few associated questions and challenges. Longer intervals between doses will improve feasibility for scale-up of this treatment, and data to support this approach are expected soon in the ATLAS-2M trial, which is evaluating a dosing schedule of every 8 weeks for combined injectable cabotegravir and rilpivirine. Also differentiated models of care, in which injections could be provided outside the conventional clinic setting, deserve evaluation. Mechanisms to provide oral bridging therapy for people who are late for injections, as was provided in the trials, will also need to be developed. In addition, close monitoring of the early clinical experience will be vital for an understanding of the “forgiveness” of this regimen when dosing is delayed, ensuring that virologic failure with resistance remains a rare event. Also plans to carefully monitor resistance as this treatment is rolled out will be needed, especially if virologic failure occurs as a result of delays in receipt of regular injections.

 

It points out that though the incidence of injection-site reactions was high (81% to 86%), few participants stopped receiving injections for this reason during the first 48 weeks, showing that the benefits of not taking a daily oral pill outweighed this inconvenience in the first year of treatment, but it questions whether this trade-off will become less acceptable over time. Therefore the development of long-acting treatment options that can be delivered less frequently than once a month remains a priority until a cure is found.

 

It concludes that the ATLAS and FLAIR trials are important milestones in the development of HIV therapeutics and represent major steps into the era of long-acting ART.