Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials

• Published in: Journal of acquired immune deficiency syndromes (1999) Vol. 85; no. 4; pp. 498 - 506
• Main Authors: Rizzardini, Giuliano, Overton, Edgar T., Orkin, Chloe, Swindells, Susan, Arasteh, Keikawus, Górgolas Hernández-Mora, Miguel, Pokrovsky, Vadim, Girard, Pierre-Marie, Oka, Shinichi, Andrade-Villanueva, Jaime F., Richmond, Gary J., Baumgarten, Axel, Masiá, Mar, Latiff, Gulam, Griffith, Sandy, Harrington, Conn M., Hudson, Krischan J., St. Clair, Marty, Talarico, Christine L., Patel, Parul, Cutrell, Amy, Van Eygen, Veerle, D'Amico, Ronald, Mrus, Joseph M., Wu, Sterling, Ford, Susan L., Chow, Ken, Roberts, Jeremy, Wills, Angela, Walters, Nicola, Vanveggel, Simon, Van Solingen-Ristea, Rodica, Crauwels, Herta, Smith, Kimberly Y., Spreen, William R., Margolis, David A.
• Format: Journal Article
• Language: English
• Published: United States JAIDS Journal of Acquired Immune Deficiency Syndromes 01-12-2020; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; Adverse events; Aged; Algorithms; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Clinical Science; Delayed-Action Preparations; Drug Combinations; Female; HIV; HIV Infections - drug therapy; HIV-1; Human immunodeficiency virus; Humans; Injection; Male; Middle Aged; Mutation; Ribonucleic acid; Rilpivirine - administration & dosage; Rilpivirine - adverse effects; Rilpivirine - therapeutic use; RNA; Safety; Sexually transmitted diseases; STD; Young Adult
• ISSN: 1525-4135; 1944-7884
• DOI: 10.1097/QAI.0000000000002466

Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1.
ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies.
Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints.
The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm.
This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.