Cabotegravir plus Rilpivirine for Persons with HIV and Adherence Challenges

BACKGROUND: Randomized trials of long-acting injectable antiretroviral therapy (ART) in persons with human immunodeficiency virus (HIV) who face challenges with adherence to oral medication are lacking. METHODS: We conducted an open-label, randomized trial involving 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). Participants received up to 24 weeks of adherence support, conditional economic incentives, and standard care with oral ART (step 1). Participants who had an HIV-1 RNA level of 200 copies per milliliter or lower in step 1 were randomly assigned in a 1:1 ratio to either continue standard care or switch to monthly injections of long-acting cabotegravir plus rilpivirine with or without oral lead-in therapy (step 2). The primary outcome was regimen failure, defined as confirmed virologic failure (two consecutive HIV-1 RNA measurements of >200 copies per milliliter) or treatment discontinuation during step 2. RESULTS: In step 1 of the trial, we enrolled 453 participants; the median age was 40 years, 63% were Black, and 29% had been assigned female sex at birth. In step 2, a total of 306 participants underwent randomization; 152 were assigned to receive cabotegravir-rilpivirine and 154 to receive standard care. Step 2 randomization was stopped early on the basis of the superiority of cabotegravir-rilpivirine to standard care in secondary outcomes at a prespecified analysis performed after a median follow-up of 48 weeks. The cumulative incidence of regimen failure by week 48 was 22.8% in the cabotegravir-rilpivirine group and 41.2% in the standard-care group (difference, -18.4 percentage points; 98.4% confidence interval [CI], -32.4 to -4.3; P = 0.002). The cumulative incidence of an adverse event was 43.5% in the cabotegravir-rilpivirine group and 42.4% in the standard-care group (difference, 1.1 percentage points; 95% CI, -12.7 to 15.0). Resistance-associated mutations developed in 2 participants with confirmed virologic failure in each group. CONCLUSIONS: Monthly injections of long-acting cabotegravir-rilpivirine were superior to standard oral ART in reducing the risk of regimen failure among persons with HIV who had adherence challenges. (Funded by the National Institute of Allergy and Infectious Diseases; LATITUDE ClinicalTrials.gov number, NCT03635788.).