Switch to ATV + r-containing regimen - SWAN - SLOAT

 Design  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 Switch to ATV+r qd* + continue other ARVs Continue previous PI regimen + other ARVs * ATV 400 mg, or ATV/r 300/100 mg if TDF part of NRTI backbone Randomisation 2: 1 Open-label 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/mm 3 N = 141 N = 278 W48 SWAN Study: switch PI+r to ATV+r Gatell J, CID 2007;44: SWAN

 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 Study: switch PI+r to ATV+r ATV+r, N = 278 Comparator PI, N = 141 Median age, years4041 Female16%21% History of AIDS diagnosis27%31% Hepatitis B and/or C co-infection32%31% Duration of prior PI treatment, mean years HIV-1 RNA at randomisation (baseline), median log 10 c/mL1.69 CD4 cell count at baseline, median/mm Discontinuation before W48, n (%)40 (14%)27 (19%) For adverse event178 For lack of efficacy12 Baseline characteristics and patient disposition Gatell J, CID 2007;44: SWAN

Gatell J, CID 2007;44: SWAN SWAN Study: switch PI+r to ATV+r Virologic rebound (HIV-1 RNA ≥ 50 c/mL) Treatment failure p = 0,004 p = 0,53 p < 0,001 p = 0,004 7% 8% 5% 16% 11% 22% 21% 34% 19/27822/141 12/1508/767/12814/6559/27848/141 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 Study: switch PI+r to ATV+r Gatell J, CID 2007;44: SWAN ATV group Comparator PI group ATV group Comparator PI group Baseline Weeks Patients not experiencing virologic rebound,% Hazard Ratio estimate (95% CI): 0.42 ( ) ; p = Patients not experiencing treatment failure,% Baseline Weeks Hazard Ratio estimate (95% CI): 0.59 ( ) ; p = 0.008

SWAN Study: switch PI+r to ATV+r Gatell J, CID 2007;44: SWAN HDL-C,high density lipoprotein cholesterol ; LDL-C, low-density lipoprotein cholesterol ; PI, protease inhibitor ; TC, total cholesterol Mean changes from baseline in lipid parameters at W48 ATV group Comparator PI group TCHDL-CFasting TGNon-HDL-C Mean mg/dL at baseline Mean mg/dL at Week Fasting LDL-C p = 0.18 p < p = 0.62 p < % -5% -3% -15% -3% -1% -33% -18% -3% 9%

 AST and ALT elevations were more frequent in patients with hepatitis co-infection SWAN Study: switch PI+r to ATV+r ATV groupComparator PI Death05 Serious adverse event27 (10%)9 (6%) Discontinuation because of adverse event17 (6%)8 (6%) Scleral icterus8 (3%)0 Jaundice7 (3%)0 Abdominal pain6 (2%)2 (2%) Grade 3-4 ALT elevation12 (4%)8 (6%) Grade 3-4 AST elevation7 (3%)4 (3%) Grade 3-4 total bilirubin elevation116 (43%)4 (3%) Gatell J, CID 2007;44: SWAN Adverse events by W48

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 Gatell J, CID 2007;44: SWAN