1. Comparison of PI vs PI  ATV vs ATV/r BMS 089  LPV/r mono vs LPV/r + ZDV/3TC MONARK  LPV/r QD vs BID M02-418 M05-730 A5073  LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL  ATV/r vs FPV/r ALERT  FPV/r vs LPV/r KLEAN  SQV/r vs LPV/r GEMINI  ATV/r vs LPV/r CASTLE  DRV/r vs LPV/r ARTEMIS

2. Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL  Design  Objective –Non inferiority of LPV/r + 3TC at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower limit of the 95% CI for the difference = -12%, 85% power) LPV/r 400/100 mg + 3TC 150 mg BID LPV/r 400/100 mg BID + FDC of 2 NRTI** Randomisation* 1 : 1 Open-label > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count HBsAg negative No R to study drugs *Randomisation was stratified by HIV RNA ( 100,000 c/mL) at screening GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI N = 209 N = 217 W48W96 ** Investigator-selected NRTI : ZDV/3TC = 54%, TDF/FTC = 37%, ABC/3TC = 9%

3. LPV/r + 3TC N = 214 LPV/r + 2 NRTI N = 202 Median age, years3435 Female16%17% HIV RNA (log 10 c/mL), median4.87 HIV RNA > 100,000 c/mL44%43% CD4 cell count (/mm 3 ), median319329 CD4 < 200 per mm 3 21%19% Discontinuation by W4816 (7.5%)27 (13.4%) For virologic failure at week 24N = 1N = 6 For adverse eventN = 1N = 10 Lost to follow-upN = 7N = 9 Non-complianceN = 5N = 1 DeathN = 10 Opportunistic infection0N = 1 PregnancyN = 10 Baseline characteristics and patient disposition Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI

4. Median CD4/mm 3 increase : + 227 (LPV/r + 3TC) vs + 217 (LPV/r + 2 NRTI) Response to treatment at week 48 Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL LPV/r + 3TC LPV/r + 2 NRTI HIV RNA < 50 c/mL 25 50 100 75 88.3 83.7 % Adjusted difference (95% CI)= 4.6% (- 2.2 ; 11.8) 95.5 96.6 Primary analysis All patients Adjusted difference (95% CI)= - 1.1% (- 5.6 ; 3.4) ITT, snapshotObserved Baseline HIV-1 RNA ≥ 100 000 c/mL 87.2 77.9 Adjusted difference (95% CI)= 9.3%(- 2.8 ; 21.5) ITT, snapshot 0 All patients

5. GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI LPV/r + 3TCLPV/r + 2 NRTI Virologic failure1012 At week 2416 At week 4896 Median HIV-1 RNA at virologic failure, c/mL2361027 Success of amplification for genotype testing5/107/12 Presence of resistance mutations20 M184V Protease inhibitor resistance 2020 ----  Virologic failure definition -2 consecutive HIV-1 RNA > 400 c/mL at or after W24 -HIV-1 RNA > 50 c/mL at W48 Resistance data at week 48 Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL

6. LPV/r + 3TCLPV/r + 2NRTIP Grade 2-3 AE possibly or probably drug related65 (30%)88 (44%)0.007 Patients with grade 2-3 AE possibly or probably drug related 4348- Drug-related AE ≥ 2% in either group Hyperlipidaemia2316- Diarrhoea14 - Nausea290.05 Dyspepsia260.02 AE leading to discontinuation2 (1%)11 (5%)*0.01 NRTI related - Zidovudine - Tenofovir 011 10 (anaemia = 3, GI, N = 6, rash = 1) 1 (rash)  Adverse events Selected grade 3-4 laboratory abnormalities occurred at the same frequency in both groups, except for hyperlipidemia (more frequent in dual therapy group) Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL GARDEL Study: LPV/r + 3TC vs LPV/r + 2 NRTI

7.  Summary –LPV/r + 3TC dual therapy was virologically non inferior to a standard therapy of LPV/r + 2 NRTI –Similar virologic response of the 2 regimens in patients with HIV RNA > 100 000 c/mL at enrolment –No resistance mutations to protease inhibitor at virologic failure in either group 2 patients with M184V in dual therapy group –Incidence of adverse events higher in triple therapy group –Discontinuation because of adverse events mainly related to NRTI in the LPV/r + NRTI arm –Potential advantages of first-line LPV/r + 3TC Cost Less toxicity (might need less monitoring) Spares the other NRTIs Cahn P. Lancet Infect Dis 2014;14:572-80 GARDEL