FLAIR Study: LA cabotegravir + rilpivirine for maintenance

Orkin C. CROI 2019, Abs. 140LB; Murray M, IAS 2019, Abs. MOPEB258

Type of ARV Trial
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» Switch to INSTI + NNRTI


  • Conclusion
    • IM injections of CAB LA + RPV LA every 4 weeks was non inferior to daily oral DTG/ABC/3TC at W48
      • For proportion of virologic rebound: HIV RNA ≥ 50 c/mL in 2.1% vs 2.5%
      • For proportion maintaining HIV-1 suppression
    • Three participants in each arm experienced confirmed virologic failure
      • No emergence of resistance in DTG/ABC/3TC arm
      • Emergence of both NNRTI and INSTI resistance-associated mutations in 3/3 in LA arm, all had HIV-1 subtype A1
    • Injection site reactions in the LA arm were common but mainly grade 1 or 2, with few associated discontinuations
    • Highly positive treatment satisfaction and preference outcomes with LA regimen


W -4: Confirm HIV RNA < 50 c/mL
* Loading dose at W4: CAB 600 mg + RPV 900 mg

  • If HLA-B*5701 positive: 2 alternative non-ABC NRTI allowed


  • Primary: % HIV RNA ≥ 50 c/mL at W48 of maintenance phase with monthly IM CAB LA + RPV LA (ITT, snapshot algorithm) ; non-inferiority if upper margin of a two-sided 95% CI for the difference = 6%
  • Secondary: HIV RNA < 50 c/mL at W48, safety, resistance emergence, PRO, participant’s preference of the LA regimen, W96 efficacy and safety

Baseline characteristics (ITT-maintenance exposed) and patient disposition

Virologic outcome at W48 (snapshot analysis, ITT-E)

  • Non inferiority achieved for primary and secondary endpoints

Confirmed virologic failures (CVF)

  • Defined as 2 consecutive HIV RNA ≥ 200 c/mL
  • DTG/ABC/3TC, N = 3 (W8, W12, W16): no emergence of resistance
  • CAB LA + RPV LA, N = 3

Confirmed virologic failures, CAB LA + RPV LA arm (N = 3)

  • Plasma CAB and RPV concentrations at the time of failure were below the population means

Plasma CAB and RPV trough concentrations (median, 5th and 95th percentiles)

Adverse events by W48

  • Over time, incidence of ISR decreased (from 71% at W4 to 20% at W48)
  • 99% of ISR were grade 1-2 and most (88%) resolved within ≤ 7 days (median : 3 days)

Patient reported outcomes

  • Change in satisfaction with current treatment vs induction phase treatment (HIVTSQc at W48), mean total score
    • LA CAB + RPV: 29.6/33
    • DTG/ABC/3TC: 25.5/33 (p < 0.001)
  • Participant preference at W48
    • Preferred LA: 91%
    • Preferred daily oral therapy: 1%

Acceptability of injection site reaction and pain

Participants with ISR