ATLAS Study: LA cabotegravir + rilpivirine for maintenance

Swindells S. CROI 2019, Abs. 139; Murray M, IAS 2019, Abs. MOAB0103

Type of ARV Trial
Switch studies in virologically suppressed patients
» Switch to INSTI + NNRTI
» CAB LA + RPV LA IM
Drugs
CAB LA, RPV LA, ABC/3TC

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  • Conclusion
    • IM injections of CAB LA + RPV LA every 4 weeks was non inferior to daily oral ART at W48
      • For proportion of virologic rebound: HIV RNA ≥ 50 c/mL in 1.6% vs 1.0%
      • For proportion maintaining HIV-1 suppression
    • Low rate (1%) of virologic failure in each arm
      • No emergence of resistance in cART arm
      • 2 of 3 participants on LA arm had NNRTI RAMs in baseline PBMCs, emergence of major INSTI resistance in 1/3
    • Injection site reactions in the LA arm were common but mainly grade 1 or 2, with few associated discontinuations
    • Significant greater increase in treatment satisfaction with LA regimen

Design


* INSTI-based regimen capped at 40% (DTG/ABC/3TC excluded)
** Loading dose at W4: CAB 600 mg + RPV 900 mg

Objectives

  • Primary: % HIV RNA ≥ 50 c/mL at W48 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

Baseline characteristics (ITT-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 = 4 (W20, W20, W32, W40): 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 69% at W4 to 11% 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 (HIVTSQs), adjusted mean change from baseline at W44
    • LA CAB + RPV: + 6.12
    • Continuation cART: + 1.05 (p < 0.001)
  • Participant preference at W48
    • Preferred LA: 86%
    • Preferred daily oral therapy: 2%

Acceptability of injection site reaction and pain

Participants with ISR