TY - JOUR
T1 - Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy
T2 - Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials
AU - Rizzardini, Giuliano
AU - Overton, Edgar T.
AU - Orkin, Chloe
AU - Swindells, Susan
AU - Arasteh, Keikawus
AU - Górgolas Hernández-Mora, Miguel
AU - Pokrovsky, Vadim
AU - Girard, Pierre Marie
AU - Oka, Shinichi
AU - Andrade-Villanueva, Jaime F.
AU - Richmond, Gary J.
AU - Baumgarten, Axel
AU - Masiá, Mar
AU - Latiff, Gulam
AU - Griffith, Sandy
AU - Harrington, Conn M.
AU - Hudson, Krischan J.
AU - St Clair, Marty
AU - Talarico, Christine L.
AU - Patel, Parul
AU - Cutrell, Amy
AU - Van Eygen, Veerle
AU - D'Amico, Ronald
AU - Mrus, Joseph M.
AU - Wu, Sterling
AU - Ford, Susan L.
AU - Chow, Ken
AU - Roberts, Jeremy
AU - Wills, Angela
AU - Walters, Nicola
AU - Vanveggel, Simon
AU - Van Solingen-Ristea, Rodica
AU - Crauwels, Herta
AU - Smith, Kimberly Y.
AU - Spreen, William R.
AU - Margolis, David A.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: 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. RESULTS: 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. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.
AB - BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: 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. RESULTS: 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. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.
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U2 - 10.1097/QAI.0000000000002466
DO - 10.1097/QAI.0000000000002466
M3 - Article
C2 - 33136751
AN - SCOPUS:85095391803
VL - 85
SP - 498
EP - 506
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
SN - 1525-4135
IS - 4
ER -