TY - JOUR
T1 - Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results
T2 - a randomised, multicentre, open-label, phase 3b, non-inferiority study
AU - Overton, Edgar T.
AU - Richmond, Gary
AU - Rizzardini, Giuliano
AU - Jaeger, Hans
AU - Orrell, Catherine
AU - Nagimova, Firaya
AU - Bredeek, Fritz
AU - García Deltoro, Miguel
AU - Swindells, Susan
AU - Andrade-Villanueva, Jaime Federico
AU - Wong, Alexander
AU - Khuong-Josses, Marie Aude
AU - Van Solingen-Ristea, Rodica
AU - van Eygen, Veerle
AU - Crauwels, Herta
AU - Ford, Susan
AU - Talarico, Christine
AU - Benn, Paul
AU - Wang, Yuanyuan
AU - Hudson, Krischan J.
AU - Chounta, Vasiliki
AU - Cutrell, Amy
AU - Patel, Parul
AU - Shaefer, Mark
AU - Margolis, David A.
AU - Smith, Kimberly Y.
AU - Vanveggel, Simon
AU - Spreen, William
N1 - Funding Information:
We thank everyone who has contributed to the success of the study: all study participants and their families, and the ATLAS-2M clinical investigators and their staff. Professional medical writing and editorial assistance was provided by Daniel Williams MSc, funded by ViiV Healthcare.
Funding Information:
ETO has received research support to his institution during the conduct of this study, and has served as a consultant for Gilead, Merck, Theratechnologies, and ViiV Healthcare, outside of the submitted work. GRic received grants from Gilead, Merck, TaiMed, and ViiV Healthcare, outside the submitted work. GRiz has received grants and personal fees from Gilead, MSD, and ViiV Healthcare; grants from Janssen, outside of the submitted work. HJ has received research lecture sponsorships or has served as a consultant or speaker on advisory boards for AbbVie, Gilead, GlaxoSmithKline, Janssen-Cilag, MSD Sharp & Dohme, TAD, and ViiV Healthcare. CO reports personal fees (for expert panels) from ViiV Healthcare during the conduct of the study. FN reports personal fees from GlaxoSmithKline during the conduct of the study. MGD reports grants from Janssen, Pharmaceutical Companies of Johnson & Johnson, and ViiV Healthcare, outside the submitted work. SS reports grants from ViiV Healthcare, during the conduct of the study. FB, JFA-V and M-AK-J have nothing to disclose. AW reports grants and personal fees from Gilead, Merck, and ViiV Healthcare, outside the submitted work. RVS-R is an employee of Janssen R&D and reports personal fees from Janssen, Pharmaceutical Companies of Johnson & Johnson. VvE is an employee of Janssen, Pharmaceutical Companies of Johnson & Johnson. HC and SV are employees and stockholders of Janssen, Pharmaceutical Companies of Johnson & Johnson. SF is an employee and stockholder of GlaxoSmithKline, outside the submitted work. CT, MS, AC, PP, VC, PB, KJH, DAM, KYS, and WS are employees of ViiV Healthcare and stockholders of GlaxoSmithKline. YW is an employee and stockholder of GlaxoSmithKline.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/12/19
Y1 - 2020/12/19
N2 - 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 ≥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 ≥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 (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. 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.
AB - 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 ≥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 ≥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 (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred. 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.
UR - http://www.scopus.com/inward/record.url?scp=85098468556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098468556&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(20)32666-0
DO - 10.1016/S0140-6736(20)32666-0
M3 - Article
C2 - 33308425
AN - SCOPUS:85098468556
VL - 396
SP - 1994
EP - 2005
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10267
ER -