1. Switch to ATV-containing regimen  ARIES Study  INDUMA Study  ASSURE Study

2.  Design  Endpoints –Primary: non inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W48 of the maintenance phase (intent-to-treat, exposed analysis), lower limit of the 95% CI for the difference = -12%, 90% power –Secondary: treatment failure, CD4, fasting lipids, adverse events Continue ATV/r + ABC/3TC Switch to ATV 400 mg qd + continue ABC/3TC * Randomisation if 2 consecutive HIV-1 RNA < 50 c/mL prior to W36 ; randomisation stratified on baseline viral load (< 100.000 or ≥ 100.000 c/mL) Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV Randomisation* 1 : 1 Open-label HIV+≥ 18 years ARV-naïve HLA-B*5701-negative HIV-1 RNA ≥ 1000 c/mL Any CD4 HBs Ag-negative N = 210 N = 209 W84 ATV/r 300/100 mg qd + ABC/3TC qd fdc Induction phase 36 weeks Maintenance phase 48 weeks N = 515

3. ATV/r N = 209 ATV N = 210 Median age, years3937 Female15%16% History of Class C AIDS events8%16% Hepatitis C co-infection6%5% Median HIV-1 RNA at baseline of induction phase, log 10 c/mL 5.065.05 CD4 cell count at baseline of induction phase, median/mm 3 204197 Discontinuation between W36 and W84, n (%)24 (11.5%)16 (7.6%) For adverse event52 For virologic failure11 Baseline characteristics and patient disposition Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV

4. Outcome at week 48 of the maintenance phase ATV/r ATV 81 86 ITT-e (TLOVR) % 0 20 40 60 80 100 HIV RNA < 50 c/mLOther endpoints 95% CI for the difference = -1.75 ; 12.48 Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV  HIV-1 RNA < 50 c/mL at W48 of the maintenance phase according to baseline plasma viral load Baseline HIV-1 RNAATV/rATV < 100.000 c/mL79%85% > 100.000 c/mL82%87%  Per-protocol virologic failure (confirmed HIV-1 RNA > 400 c/mL after achieving < 400 c/mL) –ATV/r, N = 7 –ATV, N = 1 –No major PI-resistance mutations at failure

5. ATV/rATV All events (maintenance phase)29 (14%)22 (10%) Hyperbilirubinemia20 (10%)9 (4%) Serious adverse events (Baseline to W84) All events6 (3%)1 (< 1%) Suspected ABC hypersensitivity40 Cerebrovascular accident10 Peripheral vascular disorder10 Diarrhoea01 Headache01 Hyperbilirubinemia01 Nausea01 Vomiting01 Grades 2 to 4 drug-related adverse events (frequency ≥ 3%) and serious adverse events (intent-to-treat exposed) Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV

6. ATV/r, N = 209ATV, N = 210 NMedianN p Total cholesterol Baseline188154186153 < 0.001 Week 36186181187186 Week 84175189176173 LDL cholesterol Baseline1858618188 0.006 Week 3617296174103 Week 8416910217395 HDL cholesterol Baseline1883818638 0.615 Week 361864518747 Week 841754817648 Triglycerides Baseline188123186123 < 0.001 Week 36186160187163 Week 84175153176123 Fasting lipids (mg/dL), observed analysis (intent-to-treat exposed) Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV

7.  Conclusions –ATV + ABC/3TC Is potent and well tolerated in patients who have achieved initial virologic suppression on a 36 weeks induction regimen of ATV/r + ABC/3TC Represents a viable treatment simplification strategy –Limitations Such a strategy is restricted to NRTI backbone such as ABC/3TC (TDF may lead to decrease in ATV levels and is therefore not recommended) Unboosted ATV may offer less forgiveness than ritonavir-boosted ATV Squires K, AIDS 2010;24:2019-27 ARIES ARIES Study: Switch ATV/r to ATV

8. Squires K, IAS 2011, Abs. MOPE215 HIV RNA < 50 c/mL at W144, ITT 0 TLOVRM/D = FObserved 20 60 100 40 80 77 73 78 92 94 80 % ATV/r ATV (N = 189) ATV/r (N = 180) Grade 2 to 4 AE 13%23% Hyperbilirubinemia 6%14% Drug-related AE between W36-W144  ATV, N = 2  ATV/r, N = 1 Emergence of resistance mutations ARIES Study: Switch ATV/r to ATV ARIES

9. Median values of fasting lipids, mg/dL W0-W36: all patients received induction therapy with ABC/3TC + ATV/r ARIES Study: Switch ATV/r to ATV ARIES Weeks Total cholesterol 200 mg/dL LDL-C HDL-C Triglycerides 0 40 120 200 80 160 036 130 mg/dL 40 mg/dL 150 mg/dL 152 153 186 181 182 183 88 85 104 99 98 37 39 46 45 49 51 127 123 163 160 121 151 144036144036144036144 NCEP thresholdsATV/rATV (from W36) Squires K, IAS 2011, Abs. MOPE215