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

M05-730A5073

LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL ATV/r vs FPV/r ALERT ATV/r vs DRV/r ATADAR FPV/r vs LPV/r KLEAN SQV/r vs LPV/r GEMINI ATV/r vs LPV/r CASTLE DRV/r vs LPV/r ARTEMIS

MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC Design

Delfraissy JF. AIDS 2008;22:385-93

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 yearsARV-naïve

HIV RNA < 100,000 c/mLCD4 cell count > 100/mm3

Adults > 18 yearsARV-naïve

HIV RNA < 100,000 c/mLCD4 cell count > 100/mm3

N = 54

N = 84

RandomisationOpen-label

RandomisationOpen-label

LPV/r 400/100 mg BID

LPV/r 400/100 mg BID+ ZDV/3TC BID

W96W96

LPV/rN = 84

LPV/r + ZDV/3TCN = 54

Treated eligible patients, N 83 53

Mean age, years 37 35

Female 29% 43%

HIV RNA (log10 c/mL), median 4.51 4.34

CD4 cell count (/mm3), median 235 224

Discontinuation before W48, N (%) 13 (16%) 12 (23%)

For adverse event 4 5

For suboptimal response 1 2

Intensified with ZDV/3TC 3 NA

Baseline characteristics and patient disposition

MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC

Delfraissy JF. AIDS 2008;22:385-93MONARK

Efficacy (HIV RNA) at weeks 24 and 48

MONARK Study: LPV/r BID monotherapy vs LPV/r BID + ZDV/3TC

Delfraissy JF. AIDS 2008;22:385-93MONARK

78

67

7775

ITT, missing and intensification = failure On treatment analysis

LPV/r (N = 83) LPV/r + ZDV/3TC (N = 53)%

0

40

60

80

100

< 400 c/mL at W24

< 50 c/mL at W48

Primary endpoint :< 400 c/mL at W24

and < 50 c/mL at W48

64

75

< 400 c/mL at W24and < 50 c/mL at W48

80

98

66 41

p = 0.02

Median CD4 increase at W48: 151/mm3 (LPV/r monotherapy) vs 159/mm3 (LPV/r + ZDV/3TC) (p = 0.65)Median CD4 increase at W48: 151/mm3 (LPV/r monotherapy) vs 159/mm3 (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;22:385-93MONARK