Switch to ATV/r monotherapy ARV-trial.com Switch to ATV/r monotherapy ATARITMO Swedish Study ACTG A5201 OREY MODAt Study 1

MODAt Study: switch to ATV/r monotherapy Design Randomisation* 1: 1 Open-label W48 W96 ≥ 18 years Stable ATV/r + 2 NRTI ≥ 48 weeks with HIV RNA < 50 c/mL > 24 weeks No previous virologic failure CD4+ nadir > 100/mm3 No PPI or H2-receptor antagonists HBs Ag negative ATV/r 300/100 mg qd + 2 NRTI (continuation) N = 51 ATV/r 300/100 mg monotherapy N = 52 * Randomisation was stratified on HIV RNA (≤ or > 100 000 c/mL) prior to ART start 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 Castagna A. AIDS 2014;28:2269-79

Baseline characteristics and disposition MODAt Study: switch to ATV/r monotherapy Baseline characteristics and disposition ATV/r + 2 NRTI N = 52 ATV/r monotherapy N = 51 Female 14% 18% Baseline CD4/mm3, median (IQR) 570 (417 – 735) 599 (457 – 774) Nadir CD4/mm3, median (IQR) 278 (183 - 364) 274 (221 – 355) Duration of HIV RNA < 50 c/mL (months), median 18 20 Duration on ATV/r + 2 NRTI (months), median 22 1st line antiretroviral therapy 71% TDF/FTC backbone 85% 90% Re-intensified before W48 with previous 2 NRTIs because of confirmed virologic rebound, N 11 Discontinued at W48, N 8 4 Adverse event 5 2 Confirmed virologic rebound - Patient’s decision / lost to follow-up 1 MODAt Castagna A. AIDS 2014;28:2269-79

MODAt Study: switch to ATV/r monotherapy Efficacy results HIV RNA < 50 c/mL at W48 (ITT) Confirmed virologic rebound ATV/r ATV/r + 2 NRTI Sub groups ATV/r + 2 NRTI N = 52 ATV/r N = 51 N 2 11 HIV RNA pre-ART > 100 000 c/mL 1 6 Nadir CD4 < 350/mm3 9 HCV co-infection Emergence of R mutations 1 (NRTI) ≠ (95% CI) -12.1 (- 27.8 ; 3.6) 100 85 73 92 20 40 60 80 44/ 52 37/ 51 47/ % 7.5 (- 4.7 ; 19.8) Re-intensification = failure = success 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 Castagna A. AIDS 2014;28:2269-79

1 arthritis + hyperuricemia 2 hematuria + proteinuria MODAt Study: switch to ATV/r monotherapy Safety, N (%) ATV/r + 2 NRTI, N = 52 ATV/r, N = 51 p Grade 3-4 clinical AEs 19 (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 0.027 Change in total cholesterol (mg/dL) from baseline at W48, median + 1 + 15 0.012 Grade 3-4 total cholesterol elevation 2 Change in LDL-cholesterol (mg/dL) from baseline at W48, median - 9 + 2 0.025 Grade 3-4 LDL-cholesterol elevation 3 Change in HLDL-cholesterol (mg/dL) from baseline at W48, median + 4 Grade 3-4 triglycerides elevation 1 Grade 3-4 hyperbilirubinemia 17 (33%) 20 (39%) 0.542 Change in eGFR at W48, median 0 ml/min/1.73m2 + 6.2 ml/min/1.73 m2 0.155 MODAt Castagna A. AIDS 2014;28:2269-79

MODAt Study: switch to ATV/r monotherapy 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/mm3 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;28:2269-79

MODAt Study: switch to ATV/r monotherapy W96 results HIV RNA < 50 c/mL ATV/r monotherapy = 64% vs ATV/r + 2 NRTI = 63% Difference (95% CI): 1.3% (-17.5 to 20.1%)  monotherapy not non inferior ATV/r monotherapy arm Median HIV RNA at viral rebound (N=14): 136 (72–376) copies/mL; No PI- or NRTI-associated resistance mutations were observed and all patients re-suppressed after reintensification Drug-related adverse events leading to discontinuation: 3 (6%) in ATV/r monotherapy arm vs 11 (21.5%) in the triple-therapy arm (p = 0.041) The 96 week adjusted mean percentage change in total proximal femur BMD was +1.16% and -1.64% in the ATV/r monotherapy arm and the triple-therapy arm, respectively (p = 0.012) MODAt Galli L. JAIDS 2016;71:1637-42