Monthly injections of long-acting formulations of cabotegravir and rilpivirine were noninferior to daily oral combination antiretroviral therapy (CAR) for maintaining HIV-1 suppression and also offered improved treatment satisfaction, according to research presented at the 10th IAS Conference on HIV Science, held July 21 to 24, in Mexico City, Mexico.
ATLAS and FLAIR are 2 international, open-label, randomized, phase 3 studies designed to compare switching to monthly intramuscular injections of cabotegravir + rilpivirine with continuing oral CAR. Virologically suppressed (HIV-1 RNA <50 copies/mL) participants were randomly assigned 1:1 to switch to long-acting cabotegravir + rilpivirine injections or continue CAR.
These studies reached the primary endpoint analysis at week 48, and this presentation reported a pooled and subgroup analysis of study data. In the cabotegravir + rilpivirine arm, participants received once-daily oral cabotegravir 30 mg + rilpivirine 25 mg for the first 4 weeks to determine tolerability and safety before beginning monthly injections. The primary endpoint was week 48 antiviral efficacy by the United States Food and Drug Administration snapshot algorithm (noninferiority margin, 4% for HIV-1 RNA ≥ 50 c/mL). Tolerability, safety, health outcomes, and confirmed virologic failure (2 consecutive HIV-1 RNA ≥200 copies/mL) were secondary endpoints.
The pooled intention-to-treat-exposed population included 591 participants (28% women, 19% aged ≥ 50 years) in each treatment group. Criteria for noninferiority at week 48 were met for the primary endpoint and key secondary endpoints (HIV‑1 RNA < 50 copies/mL). In each group, 7 participants (1.2%) experienced confirmed virologic failure, with 6 individuals in the cabotegravir + rilpivirine group and 3 participants in the CAR group demonstrating resistance mutations. Similar treatment effects on rates of HIV-1 RNA ≥ 50 copies/mL (long acting injectable medications vs CAR) were seen across subgroups, thereby supporting the overall conclusion.
Most cabotegravir + rilpivirine participants (83%) developed injection site reactions that decreased over time, but in 6 participants (1%) it led to withdrawal. In each group, the serious adverse event rate was 4%. cabotegravir + rilpivirine participants reported significant increases in treatment satisfaction compared with CAR therapy at weeks 24 and 44.
Study investigators concluded, “This pooled analysis demonstrates that monthly injections of [long-acting cabotegravir + rilpivirine] were non-inferior to daily oral CAR for maintaining HIV-1 suppression, and provided improved treatment satisfaction.”
Further, Murray, et al presented data on patient views and self-reported outcomes of both the ATLAS2 and FLAIR3 trials. Of the 616 individuals who participated in the ATLAS trial, 94% of the 308 participants who received the long-acting cabotegravir + rilpivirine injectable reported satisfaction with and a desire to continue treatment with the injectable, compared with 66% of the participants who received daily oral combination antiretroviral therapy. In addition, 86% of participants in the cabotegravir + rilpivirine group reported that the pain associated with the injection was either “totally” or “very” acceptable. Of the 566 participants in the FLAIR trail, 283 received the long-acting cabotegravir + rilpivirine injectable. At week 48, 91% of these participants reported a preference to stay on the injectable and 1% stated they would rather receive treatment with the oral combination antiretroviral. In addition, 287 of the cabotegravir + rilpivirine group reported high levels of tolerability of pain associated with the injection.
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
1. Overton ET, Orkin C, Swindells S, et al. Monthly long-acting cabotegravir and rilpivirine is non-inferior to oral ART as maintenance therapy for HIV-1 infection: Week 48 pooled analysis from the Phase 3 ATLAS and FLAIR studies. Presented at: The 10th IAS Conference on HIV Science; July-21-24, 2019; Mexico City, MX. Abstract 1291.
2. Murray M, Antela A, Mills A, et al. Patient views on long acting HIV treatment: cabotegravir + rilpivirine as maintenance therapy (ATLAS 48 week results). Presented at: The 10th IAS Conference on HIV Science; July-21-24, 2019; Mexico City, MX. Abstract 3680.
3. Murray M,Bernal E, Chounta V, et al. Patient-reported outcomes on long-acting cabotegravir + rilpivirine as maintenance therapy: FLAIR 48-Week results. Presented at: The 10th IAS Conference on HIV Science; July-21-24, 2019; Mexico City, MX. Abstract 2373.