Switch to ATV/r monotherapy  ATARITMO  Swedish Study  ACTG A5201  OREY  MODAt Study

ATV/r 300/100 mg qd + 2 NRTI (continuation) N = 51 N = 52 ATV/r 300/100 mg monotherapy  Design Randomisation* 1: 1 Open-label  Objective –Primary Endpoint : proportion with treatment success at W48 Treatment failure : treatment discontinuation for any cause or confirmed virologic rebound (first of 2 consecutive HIV RNA > 50 c/mL within 2 weeks) Non-inferiority of ATV/r (ITT analysis) ; lower limit of the 2-sided 95% CI for the difference = -10% ; sample size = 342 (171 x 2), 80% power Interim analysis by IDMC in June 2013 : recommendation to stop further enrolment MODAT ≥ 18 years Stable ATV/r + 2 NRTI ≥ 48 weeks with HIV RNA 24 weeks No previous virologic failure CD4+ nadir > 100/mm 3 No PPI or H2-receptor antagonists HBs Ag negative W48W96 MODAt Study: switch to ATV/r monotherapy * Randomisation was stratified on HIV RNA (≤ or > 100,000 c/mL) prior to ART start Castagna A. AIDS 2014;28:

Baseline characteristics and disposition ATV/r + 2 NRTI N = 52 ATV/r monotherapy N = 51 Female14%18% Baseline CD4/mm 3, median (IQR)570 (417 – 735)599 (457 – 774) Nadir CD4/mm 3, median (IQR)278 ( )274 (221 – 355) Duration of HIV RNA < 50 c/mL (months), median1820 Duration on ATV/r + 2 NRTI (months), median st line antiretroviral therapy71% TDF/FTC backbone85%90% Re-intensified before W48 with previous 2 NRTIs because of confirmed virologic rebound, n 011 Discontinued at W48, N84 Adverse event52 Confirmed virologic rebound2- Patient’s decision / lost to follow-up12 MODAT MODAt Study: switch to ATV/r monotherapy Castagna A. AIDS 2014;28:

HIV RNA < 50 c/mL at W48 (ITT) ATV/rATV/r + 2 NRTI Confirmed virologic rebound Efficacy results Sub groups ATV/r + 2 NRTI N = 52 ATV/r N = 51 N211 HIV RNA pre-ART > 100,000 c/mL 16 Nadir CD4 < 350/mm 3 19 HCV co-infection06 Emergence of R mutations1 (NRTI)0 MODAT Predictor of treatment failure in the ATV/r arm : HCV co-infection (HR : 7.64 ; 95% CI: 1.44 to 40.47, p = 0.017) MODAt Study: switch to ATV/r monotherapy Castagna A. AIDS 2014;28: ≠ (95% CI) ( ; 3.6) / 52 37/ 51 47/ 51 44/ 52 % ≠ (95% CI) 7.5 (- 4.7 ; 19.8) Re-intensification = failure Re-intensification = success

ATV/r + 2 NRTI,N = 52ATV/r,N = 51p Grade 3-4 clinical AEs19 (36.5%)6 (11.8%)0.003 Grade 3-4 drug-related clinical AEs 6 2 nephrolithiasis 1 cholelithiasis 1 arthritis + hyperuricemia 2 hematuria + proteinuria Change in total cholesterol (mg/dL) from baseline at W48, median Grade 3-4 total cholesterol elevation20 Change in LDL-cholesterol (mg/dL) from baseline at W48, median Grade 3-4 LDL-cholesterol elevation33 Change in HLDL-cholesterol (mg/dL) from baseline at W48, median Grade 3-4 triglycerides elevation11 Grade 3-4 hyperbilirubinemia17 (33%)20 (39%)0.542 Change in eGFR at W48, median0 ml/min/1.73m ml/min/1.73 m Safety, N (%) MODAT MODAt Study: switch to ATV/r monotherapy Castagna A. AIDS 2014;28:

 Conclusion – ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy with ATV/r + 2 NRTI Inferiority more pronounced in those with – Pre-ART HIV RNA > 100,000 c/mL – Nadir CD4 < 350/mm 3 – HCV co-infection No benefits of ATV/r monotherapy on lipids or renal function – NRTIs re-intensification was effective in all the individuals – The study was terminated early due to recommendation of IDMC MODAT Castagna A. AIDS 2014;28: MODAt Study: switch to ATV/r monotherapy