Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.

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From: The Lancet(Vol. 396, Issue 10267)
Publisher: Elsevier B.V.
Document Type: Article
Length: 801 words

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Summary Background Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing. Methods ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA [greater than or equal to]50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing. Findings Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34--50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA [greater than or equal to]50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0*8 (95% CI -0*6--2*2). There were eight (2%, every 8 weeks group) and two ( Interpretation The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1. Funding ViiV Healthcare and Janssen. Author Affiliation: (a) University of Alabama at Birmingham, Birmingham, AL, USA (b) Nova Southeastern University, FL, USA (c) Fatebenefratelli Sacco Hospital, Milan, Italy (d) School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa (e) MVZ Karlsplatz, HIV Research and Clinical Care Centre, Munich, Germany (f) Desmond Tutu HIV Foundation, University of Cape Town Medical School, Cape Town, South Africa (g) Republic Center for the Prevention and Control of AIDS and Infectious Diseases, Russia (h) Metropolis Medical, San Francisco, CA, USA (i) General Hospital of Valencia, Valencia, Spain (j) University of Nebraska Medical Center, Omaha, USA (k) Hospital Civil "Fray Antonio Alcalde", Guadalajara, Mexico (l) Department of Medicine, University of Saskatchewan, Regina, Saskatchewan, Canada (m) CH - Hôpital Delafontaine, Saint-Denis, France (n) Janssen Research and Development, Janssen Pharmaceutica NV, Beerse, Belgium (o) GlaxoSmithKline, Research Triangle Park, NC, USA (p) ViiV Healthcare, Research Triangle Park, NC, USA (q) ViiV Healthcare, Brentford, UK (r) GlaxoSmithKline, Collegeville, PA, USA * Correspondence to: Dr Edgar T Overton, Community Care Building, Birmingham, AL 35294-2050, USA Byline: Edgar T Overton, MD [eoverton@uabmc.edu] (a), Gary Richmond, MD (b), Prof Giuliano Rizzardini, MD (c,d), Hans Jaeger, MD (e), Catherine Orrell, MBChB (f), Firaya Nagimova, MD (g), Fritz Bredeek, MD (h), Miguel García Deltoro, PhD (i), Susan Swindells, MBBS (j), Jaime Federico Andrade-Villanueva, MSc (k), Alexander Wong, MD (l), Marie-Aude Khuong-Josses, MD (m), Rodica Van Solingen-Ristea, MD (n), Veerle van Eygen, MSc (n), Herta Crauwels, PhD (n), Susan Ford, Pharm D (o), Christine Talarico, MS (p), Paul Benn, FRCP (q), Yuanyuan Wang, PhD (r), Krischan J Hudson, PhD (p), Vasiliki Chounta, MSc (q), Amy Cutrell, MS (p), Parul Patel, Pharm D (p), Mark Shaefer, Pharm D (p), David A Margolis, MD (p), Kimberly Y Smith, MD (p), Simon Vanveggel, MSc (n), William Spreen, Pharm D (p)

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Gale Document Number: GALE|A648881994