FRIDAY, Feb. 27, 2026 (HealthDay News) -- Monthly injections of long-acting cabotegravir-rilpivirine are superior to standard oral antiretroviral therapy (ART) in persons with human immunodeficiency virus (HIV) and medication adherence challenges, according to a study published online Feb. 18 in the New England Journal of Medicine.Aadia I. Rana, M.D., from the University of Alabama at Birmingham, and colleagues enrolled 453 persons with HIV who had inadequate adherence to ART (a persistent HIV-1 RNA level of >200 copies per milliliter or loss to follow-up) to 24 weeks of adherence support, conditional economic incentives, and standard care with oral ART as part of step 1. Then, in step 2, the 306 participants achieving an HIV-1 RNA level of ≤200 copies per milliliter were randomly assigned to continue standard care (154 participants) or switch to monthly injections of long-acting cabotegravir plus rilpivirine with or without oral lead-in therapy (152 participants).The researchers reported that step 2 randomization was stopped early on the basis of the superiority of cabotegravir-rilpivirine to standard care at a prespecified analysis. By week 48, the cumulative incidence of regimen failure was 22.8 percent in the cabotegravir-rilpivirine group and 41.2 percent in the standard-care group. For adverse events, the cumulative incidence was 43.5 percent in the cabotegravir-rilpivirine group versus 42.4 percent in the standard-care group. Two participants in each group developed resistance-associated mutations with confirmed virologic failure."These findings have the potential to validate a long-acting approach for this additional group of patients and could make a significant difference to people living with HIV and our goal of ending the epidemic," Kimberly Smith, M.D., head of research & development at ViiV Healthcare, said in a statement.Several authors disclosed ties to ViiV Healthcare, the maker of cabotegravir-rilpivirine.Abstract/Full TextEditorial (subscription or payment may be required).Sign up for our weekly HealthDay newsletter