NRTI-sparing  SPARTAN  PROGRESS  RADAR  NEAT001/ANRS 143  A  VEMAN  MODERN

A Study: ATV/r + MVC vs ATV/r + TDF/FTC  Design ≥ 16 years HIV+ Antiretroviral naive HIV-1 RNA ≥ c/mL CD4 ≥ 100/mm 3 CCR5-tropic (Trofile®) No resistance to TDF, FTC or ATV HBV co-infection excluded ≥ 16 years HIV+ Antiretroviral naive HIV-1 RNA ≥ c/mL CD4 ≥ 100/mm 3 CCR5-tropic (Trofile®) No resistance to TDF, FTC or ATV HBV co-infection excluded ATV/r 300/100 qd + MVC 150 qd ATV/r + TDF/FTC 118 N = 60 N = 61 Randomisation 1 : 1 Open-label W96  Objective Primary endpoint: % with HIV RNA < 50 c/mL at W48 (ITT, missing, discontinued = failure), not powered to show a difference Protocol-defined treatment failure: c/mL on 2 consecutive measurements ≤ 14 days apart in patients having achieved levels < 400 c/mL on 2 consecutive visits Mills A. JAIDS 2013;62: A

ATV/r + MVC N = 60 ATV/r + TDF/FTC N = 61 Age, years3835 Female, %715 CD4/mm HIV RNA, log 10 copies/mL Discontinuation by W48, n For adverse event For lack of efficacy Switch from ATV/r due to jaundice, n Switch to DRV/r Switch to LPV/r Baseline characteristics (mean), and disposition A Study: ATV/r + MVC vs ATV/r + TDF/FTC Mills A. JAIDS 2013;62: A

Median change from baseline in CD4 cell count/mm 3 at W48: for MVC vs for TDF/FTC HIV-1 RNA < 50 c/mL at W48, ITT, missing/discontinuation = failure Mills A. JAIDS 2013;62: A A Study: ATV/r + MVC vs ATV/r + TDF/FTC  Genotype analysis : 3 patients in each group with HIV RNA ≥ 500 c/mL at time of discontinuation : –no resistance to any component –no change in tropism in MVC group ATV/r + MVC ATV/r + TDF/FTC < 100,000 copies/mL N= 43 > 100,000 copies/mL Baseline HIV-1 RNA %

ATV/r + MVC N = 60 ATV/r + TDF/FTC N = 61 Discontinuation due to adverse event, n 2 Vomiting, jaundice 0 Adverse event in ≥ 10% of patients, % Hyperbilirubinemia Diarrhea Upper respiratory tract infection Nausea Vomiting Headache Grade 3-4 adverse event, % Serious adverse event, % attributed to ATV 16.7 N = 1 (nephrolithiasis) Hyperbilirubinemia grade 3 / grade 4, %50.8 / / 4.9 ALAT grade 3-4 / ASAT grade 3-4, %5.1 / / 3.2 Change from baseline in mean creatinine clearance (Cockroft-Gault formula), mL/min Safety at W48 Mills A. JAIDS 2013;62: A A Study: ATV/r + MVC vs ATV/r + TDF/FTC

 Conclusion –This open-label study in treatment-naive patients with CCR5-tropic virus showed that a high proportion of patients in the MVC and TDF/FTC treatment groups achieved and maintained viral suppression through 48 weeks of treatment Low potential for resistance or loss of susceptibility to study drugs at treatment failure –When stratified by plasma HIV-1 RNA concentration at baseline, the number of patients who achieved plasma HIV-1 RNA < 50 c/mL at W48 was higher in the TDF/FTC + ATV/r treatment arm compared with the MVC + ATV/r group –CD4 cell counts increased from baseline in both treatment groups –The frequency of treatment-limiting hyperbilirubinemia was greater than expected –Limitations Unpowered to establish non-inferiority Mills A. JAIDS 2013;62: A