NRTI-sparing  SPARTAN  PROGRESS  NEAT001/ANRS 143  MODERN

Kozal MJ. HIV Clin Trials 2012;13;  Design  Efficacy endpoint –Primary : HIV RNA < 50 copies/mL at week 24 by mITT (confirmed virologic response (CVR) with non completers counted as failure) –Other assessments : CVR with non completers counted as missing, virologic response-observed ATV 300 mg BID + RAL 400 mg BID ATV/r mg QD + TDF/FTC Randomisation* 2 : 1 Open-label > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count No primary resistance in RT or protease *Randomisation was stratified by HIV RNA ( 100,000 c/mL) N = 30 N = 63 W24W96 SPARTAN SPARTAN Study: ATV + RAL BID vs ATV/r + TDF/FTC QD

ATV + RAL, N = 63ATV/r + TDF/FTC, N = 30 Female13%7% HIV RNA (log 10 c/mL), median CD4 cell count (/mm 3 ), mean+SE 256 ± ± 25 Discontinuation by W246 (9.5%)3 (10.0%) Withdrew consentN = 20 JaundiceN = 20 Other adverse eventsN = 2 (1 arrhythmia, 1 cancer)0 Lost to follow-up0N = 1 Protocol violation0N = 2 Baseline characteristics and patient disposition HIV RNA < 50 c/mL ATV + RALATV/r + TDF/FTC CVR, NC=F74.6%63.3% CVR, NC=M81.0%70.4% Virologic response, observed78.8%76.0% Mean CD4/mm 3 increase Response rate at week 24 Kozal MJ. HIV Clin Trials 2012;13; SPARTAN SPARTAN Study: ATV + RAL BID vs ATV/r + TDF/FTC QD

ATV + RALATV/r + TDF/FTC Virologic failure (HIV RNA > 50 c/mL)11 (17%)8 (27%) Meeting criteria for genotype testing (HIV RNA > 400 c/mL)61 Resistance mutations4/50 INSTI mutations4*- ATV mutations00  Resistance data * N = 1 with Q148R, N = 1 with Q148Q/R + T97T/A, 2 with N155H ATV + RALATV/r + TDF/FTC Grade 2-4 treatment-related adverse events19 (30%)10 (33%) Hyperbilirubinemia11 (17.5%)3 (10%) Diarrhoea02 (7%) Nausea1 (2%)1 (3%) Grade 3-4 adverse events16 (25%)6 (20%) Grade 3-4 total bilirubin elevation38 (60%)14 (47%) Adverse events leading to discontinuation 4 (6.3%) Arrhytmia, Jaundice (2), Testicular cancer 1 (3.3%) Diarrhoea  Adverse events through week 24 Kozal MJ. HIV Clin Trials 2012;13; SPARTAN SPARTAN Study: ATV + RAL BID vs ATV/r + TDF/FTC QD

 Conclusion –ATV + RAL BID achieved virologic response rate comparable to current standard of care for treatment-naïve subjects –ATV + RAL was associated with Emergence of resistance to RAL in case of virologic failure Higher rates of severe hyperbilirubinemia compared with ATV/r 300/100 mg QD –Could be related to higher ATV exposure No new or unexpected safety signals –Study was early terminated and regimen of ATV 300 mg BID + RAL 400 mg BID considered not to be optimal for further clinical development Kozal MJ. HIV Clin Trials 2012;13; SPARTAN