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Switch to INSTI + NNRTI

Investigating the switch to Cabotegravir + Rilpivirine therapy in people living with HIV. Results show non-inferiority to oral ART at Week 48. Detailed findings, virologic outcomes, and patient satisfaction. Presented at CROI 2019 and IAS 2019.

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Switch to INSTI + NNRTI

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  1. Switch to INSTI + NNRTI • Switch to DTG + RPV • SWORDStudy • Switch to CAB LA + RPV LA IM • LATTE-2 Study • FLAIR • ATLAS

  2. ATLAS Study: LA cabotegravir + rilpivirine for maintenance • Design Randomisation 1: 1 • Objective • 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 Extension Continuation of current daily oral ART(N = 308) On PI, NNRTI orINSTI-based regimen * uninterrupted > 6 months HIV RNA < 50 c/mL x 2 ≤ 12 months HIV RNA < 50 c/mL at screening CAB LA + RPV LA IM Q4W Oral CAB + RPV (N = 308 CAB LA 400 mg + RPV LA 600 mg **IM every 4 weeks (N = 303) * INSTI-based regimen capped at 40% (DTG/ABC/3TC excluded) W4 W48 W52 W96 D1 ** Loading dose at W4: CAB 600 mg + RPV 900 mg Swindells S. CROI 2019, Abs. 139 ATLAS

  3. ATLAS Study: LA cabotegravir + rilpivirine for maintenance Baseline characteristics (ITT-exposed) and patient disposition Swindells S. CROI 2019, Abs. 139 ATLAS

  4. ATLAS Study: LA cabotegravir + rilpivirine for maintenance Virologic outcome at W48 (snapshot analysis, ITT-E) Difference * (95% CI) CAB LA + RPV LA (N = 308) Primary endpoint: HIV RNA ≥ 50 c/mL % Continuation cART (N = 308) CAB LA + RPV LA cART 95.5 92.5 100 0.6 80 - 1.2 2.5 0 ‒ 10% + 6% 60 Secondary endpoint: HIV RNA < 50 c/mL 40 cART CAB LA + RPV LA - 3.0 20 5.8 3.6 0.7 - 6.7 1.6 1.0 0 0 ‒ 10% + 10% HIV RNA≥ 50 c/mL Virologic success HIV RNA < 50 c/mL No virologic data * Adjusted for gender and baseline third agent class • Non inferiority achieved for primary and secondary endpoints Swindells S. CROI 2019, Abs. 139 ATLAS

  5. ATLAS Study: LA cabotegravir + rilpivirine for maintenance • 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 Swindells S. CROI 2019, Abs. 139 ATLAS

  6. 103 ATLAS Study: LA cabotegravir + rilpivirine for maintenance Plasma CAB and RPV trough concentrations (median, 5th and 95th percentiles) 10 RPV (ng/mL), N = 308 CAB (μg/mL), N = 308 1 100 0,1 4 8 12 16 20 24 28 32 36 40 44 48 • PA-IC90(12 ng/mL) 10 • PA-IC90 (0.166 µg/mL) 4 8 12 16 20 24 28 32 36 40 44 48 Week Week Swindells S. CROI 2019, Abs. 139 ATLAS

  7. ATLAS Study: LA cabotegravir + rilpivirine for maintenance 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) Swindells S. CROI 2019, Abs. 139 ATLAS

  8. ATLAS Study: LA cabotegravir + rilpivirine for maintenance • 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% Swindells S. CROI 2019, Abs. 139 ATLAS

  9. ATLAS Study: LA cabotegravir + rilpivirine for maintenance Treatment satisfaction (HIVTSQs Questionnaire) Overall treatment acceptance (ACCEPT Questionnaire) CAB + RPV LA Continuation cART Adjusted mean change (95% CI) from baseline Adjusted mean change (95% CI) from baseline 75 Improvement 100 55 66 (max) Improvement Difference (95% CI) Difference (95% CI) W8 8.9 1.0 W24 7.9 (4.1-11.7) ; p < 0.001 5.39 (4.17-6.60) ; p < 0.001 W24 +6.43 12.3 +1.05 5.5 6.9 (3.3-10.4) ; p < 0.001 W48 13.7 W44 3.0 5.68 (4.37-6.98) ; p < 0.001 +6.12 +0.44 10.7 (7.1-14.4) ; p < 0.001 Murray M, IAS 2019, Abs. MOAB0103 ATLAS

  10. 50 ATLAS Study: LA cabotegravir + rilpivirine for maintenance Acceptability of injection site reaction and pain % *p < 0.001 *p < 0.001 Totally acceptable 100 % 3 1 4 6 Very acceptable 100 80 7 5 69 9 10 Moderately acceptable 20 80 18 23 60 31 A little acceptable 60 26 38 35 40 Not at all acceptable 27 27 40 20 19 17 17 67 16 14 14 20 11 55 29 20 48 0 0 4 Loading dose 8 12 16 20 24 28 32 36 40 44 48 ISR Pain ISR Pain W5 (1 week post-injection), N = 296 W48, N = 303 Weeks Participants with ISR Murray M, IAS 2019, Abs. MOAB0103 ATLAS

  11. ATLAS Study: LA cabotegravir + rilpivirine for maintenance • 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 Swindells S. CROI 2019, Abs. 139 ATLAS

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