Comparison of PI vs PI  ATV vs ATV/r BMS 089  LPV/r mono vs LPV/r + ZDV/3TCMONARK  LPV/r QD vs BIDM M A5073  LPV/r + 3TC vs LPV/r + 2 NRTIGARDEL  ATV/r vs FPV/rALERT  ATV/r vs DRV/rATADAR  FPV/r vs LPV/rKLEAN  SQV/r vs LPV/rGEMINI  ATV/r vs LPV/rCASTLE  DRV/r vs LPV/rARTEMIS

MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC  Design Delfraissy JF. AIDS 2008;22:  Objective –Primary endpoint: HIV RNA < 400 c/mL at W24 and < 50 c/mL at W48 –No power calculation due to limited sample size, and pilot nature of the study LPV/r soft-gel capsule was used MONARK Adults > 18 years ARV-naïve HIV RNA < 100,000 c/mL CD4 cell count > 100/mm 3 N = 54 N = 84 Randomisation Open-label LPV/r 400/100 mg BID + ZDV/3TC BID W96

LPV/r N = 84 LPV/r + ZDV/3TC N = 54 Treated eligible patients, N8353 Mean age, years3735 Female29%43% HIV RNA (log 10 c/mL), median CD4 cell count (/mm 3 ), median Discontinuation before W48, N (%)13 (16%)12 (23%) For adverse event45 For suboptimal response12 Intensified with ZDV/3TC3NA Baseline characteristics and patient disposition MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC Delfraissy JF. AIDS 2008;22: MONARK

Efficacy (HIV RNA) at weeks 24 and 48 MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC Delfraissy JF. AIDS 2008;22: MONARK ITT, missing and intensification = failure On treatment analysis LPV/r (N = 83) LPV/r + ZDV/3TC (N = 53) % < 400 c/mL at W24 < 50 c/mL at W48 Primary endpoint : < 400 c/mL at W24 and < 50 c/mL at W < 400 c/mL at W24 and < 50 c/mL at W p = 0.02 Median CD4 increase at W48: 151/mm 3 (LPV/r monotherapy) vs 159/mm 3 (LPV/r + ZDV/3TC) (p = 0.65)

 Resistance, safety and tolerability –24/136 patients qualified for resistance testing (rebound of HIV RNA > 500 c/mL): 21/83 in the LPV/r monotherapy group and 3/53 in the LPV/r + ZDV/3TC group –PI-associated resistance mutations emerged in 3/21 patients on LPV/r monotherapy (L76V, M46I) –Serious adverse event: 12% LPV/r mono vs 8% LPV/r + ZDV/3TC –Similar frequency of clinical adverse events (mainly diarrhoea) and laboratory abnormalities (transaminases elevations) of at least moderate severity in the 2 groups  Conclusion –In antiretroviral-naïve patients, LPV/r monotherapy demonstrates lower rates of virologic suppression as compared with LPV/r + ZDV/3TC –LPV/r monotherapy should not be offered for first-line antiretroviral therapy MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC Delfraissy JF. AIDS 2008;22: MONARK