Switch to ATV- or ATV/r-containing regimen ARV-trial.com Switch to ATV- or ATV/r-containing regimen Switch to ATV/r-containing regimen ATAZIP Switch to ATV ± r-containing regimen SWAN Study SLOAT Study Switch to ATV-containing regimen ARIES Study INDUMA Study ASSURE Study 1

SWAN Study: switch PI+r to ATV+r Design Randomisation 2: 1 Open-label W48 419 HIV+ patients On stable PI-based regimen ≥ 3 months (PI dosed at least bid and > 3 pills/day) No history of failure on PI therapy HIV RNA < 50 c/mL ≥ 3 months CD4 > 50/mm3 N = 278 Switch to ATV+r qd* + continue other ARVs N = 141 Continue previous PI regimen + other ARVs * ATV 400 mg, or ATV/r 300/100 mg if TDF part of NRTI backbone Objective Non inferiority in the proportion of patients with virologic rebound at W48 (upper limit of the 95% CI for the difference = 12%, 90% power) Virologic rebound: 2 consecutive HIV-1 RNA ≥ 50 c/mL on study, or last on-study HIV-1 RNA ≥ 50 c/mL followed by study discontinuation SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r ARV-trial.com SWAN Study: switch PI+r to ATV+r Baseline characteristics and patient disposition ATV+r, N = 278 Comparator PI, N = 141 Median age, years 40 41 Female 16% 21% History of AIDS diagnosis 27% 31% Hepatitis B and/or C co-infection 32% Duration of prior PI treatment, mean years 3.4 3.3 HIV-1 RNA at randomisation (baseline), median log10c/mL 1.69 CD4 cell count at baseline, median/mm3 490 489 Discontinuation before W48, n (%) 40 (14%) 27 (19%) For adverse event 17 8 For lack of efficacy 1 2 PI use at screening was LPV/r: 37%, NFV: 33%, IDV/r: 10%, IDV: 8%, SQV/r: 6%, SQV: 3% TDF was part of the ARV regimen in 37 patients (9%) [26 in the ATV group] SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r Virologic rebound (HIV-1 RNA ≥ 50 c/mL) Treatment failure 5 10 15 35 40 30 25 20 p = 0,004 p = 0,53 p < 0,001 7% 8% 5% 16% 11% 22% 21% 34% 19/278 22/141 12/150 8/76 7/128 14/65 59/278 48/141 Difference estimate (95% CI) -8.8 (-14.8 ; -2.7) -2.5 (-10.4 ; 5.3) -16.1 (-25.4 ; -6.8) -12.8 (-21.7 ; -4.0) ATV group Comparator PI group Patients on PI/r at screening All patients Patients on unboosted PI at screening % SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r 20 40 60 80 100 12 Baseline 36 24 48 Weeks Patients not experiencing virologic rebound,% Hazard Ratio estimate (95% CI): 0.42 (0.22-0.79) ; p = 0.007 Patients not experiencing treatment failure,% Hazard Ratio estimate (95% CI): 0.59 (0.40-0.87) ; p = 0.008 ATV group Comparator PI group 278 141 254 231 239 143 121 101 110 74 258 240 122 ATV group Comparator PI group SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r Mean changes from baseline in lipid parameters at W48 ATV group Comparator PI group TC HDL-C Fasting TG Non-HDL-C Mean mg/dL at baseline Mean mg/dL at Week 48 123 108 135 133 212 181 220 216 50 51 49 203 137 201 215 162 132 171 168 Fasting LDL-C -40 -30 -10 10 -20 p = 0.18 p < 0.001 p = 0.62 -12% -5% -3% -15% -1% -33% -18% 9% HDL-C,high density lipoprotein cholesterol ; LDL-C, low-density lipoprotein cholesterol ; PI, protease inhibitor ; TC, total cholesterol SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r Adverse events by W48 ATV group Comparator PI Death 5 Serious adverse event 27 (10%) 9 (6%) Discontinuation because of adverse event 17 (6%) 8 (6%) Scleral icterus 8 (3%) Jaundice 7 (3%) Abdominal pain 6 (2%) 2 (2%) Grade 3-4 ALT elevation 12 (4%) Grade 3-4 AST elevation 4 (3%) Grade 3-4 total bilirubin elevation 116 (43%) AST and ALT elevations were more frequent in patients with hepatitis co-infection SWAN Gatell J, CID 2007;44:1484-92

SWAN Study: switch PI+r to ATV+r Conclusions Switching to a simplified PI-based regimen containing ATV provided better maintenance of virologic suppression with lower rates of virologic rebound and treatment failure than those observed with continued, unmodified therapy Safety and tolerability were similar in both groups But lipid parameters improved in the ATV group Hyperbilirubinemia was frequent on ATV SWAN Gatell J, CID 2007;44:1484-92