Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy : Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
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| Enthalten in: |
Journal of acquired immune deficiency syndromes (1999) - 85(2020), 4 vom: 01. Dez., Seite 498-506 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 02.04.2021 Date Revised 02.04.2021 published: Print ClinicalTrials.gov: NCT02951052, NCT02938520 Citation Status MEDLINE |
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| doi: |
10.1097/QAI.0000000000002466 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317051032 |
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| 100 | 1 | |a Rizzardini, Giuliano |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy |b Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials |
| 264 | 1 | |c 2020 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 02.04.2021 | ||
| 500 | |a Date Revised 02.04.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02951052, NCT02938520 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1 | ||
| 520 | |a SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Delayed-Action Preparations |2 NLM | |
| 650 | 7 | |a Drug Combinations |2 NLM | |
| 650 | 7 | |a cabotegravir, rilpivirine drug combination |2 NLM | |
| 650 | 7 | |a Rilpivirine |2 NLM | |
| 650 | 7 | |a FI96A8X663 |2 NLM | |
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