switch studies in virologically suppressed patients

Switch to LPV/r monotherapy

Pilot LPV/r M03-613 LPV/r Mono KalMo OK OK04 KALESOLO MOST HIV-NAT 077

Design

Endpoints– Primary: proportion of patients with HIV-1 RNA < 50 c/mL at W96

(ITT-exposed, previous-failure = failure analysis) ; 80% power to detect a difference of 25% in response rate

– Secondary: lipoatrophy (> 20% loss in limb fat) at W96 ; 70% power to detect a 20% difference in the mean change in limb fat percentage

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

EFV 600 mg QD + ZDV/3TC

Randomisation2 : 1

Open-label

Randomisation2 : 1

Open-label

HIV+, ARV-naïveHIV-1 RNA > 1000 c/mL

Any CD4 cell countNo documented resistance

HIV+, ARV-naïveHIV-1 RNA > 1000 c/mL

Any CD4 cell countNo documented resistance N = 51

N = 104

W96W96

Cameron DW, JID 2008;198:234-40M03-613M03-613

* Patients with HIV-1 RNA < 50 c/mL on 3 consecutive measures between W24 and W48 discontinued ZDV/3TC and remained on LPV/r monotherapy

M03-613 Study: Switch to LPV/r monotherapy

LPV/r 400/100 mg bid monotherapy

*

79% of patients were male

65% were white

Mean age was 38 years

Mean baseline HIV-1 RNA was 4.9 log10 c/mL

Patients in the LPV/r group had a higher mean baseline HIV-1 RNA and a higher mean age

112 patients (57% in the LPV/r group and 69% in the EFV group) completed their assigned treatment regimen out to week 96

In the LPV/r group, after a median of 24 weeks, 92 patients (88%) simplified to LPV/r monotherapy

Cameron DW, JID 2008;198:234-40M03-613M03-613


Baseline characteristics and patient disposition

Outcome at week 96

* Confirmed virologic failure before W96 andreintensified therapy with NRTIs were ignored

EFV + ZDV/3TC

LPV/rmono

Confirmed HIV-1 RNA < 50 c/mL after 72 weeks post-simplification

91%

57%(Kaplan-

Meier estimate, p < 0.001)

Confirmed virologic rebound (HIV-1 RNA > 500 c/mL)

-

N = 124/7 achieved HIV-1 RNA< 50 c/mL after NRTI

intensification

Mean change in CD4/mm3 at W96 + 240 + 289

(p = 0.12)

Development of resistance

to EFV, N = 1

to PI, N = 4(3 on LPV/r mono*, 1 on

LPV/r + ZDV+3TC*)

Cameron DW, JID 2008;198:234-40M03-613M03-613


EFV LPV/r mono

ITT-E Non completion= failure analysis*

63 60

%

0

20

40

60

80

100

95% CI for the difference =- 29% ; 4%

61

48

95% CI for the difference =- 19% ; 13%

HIV-1 RNA < 50 c/mL

HIV-1 RNA< 50 c/mL

* major PI mutations in all 4 cases

Cameron DW, JID 2008;198:234-40M03-613M03-613


%

0

20

40

60

80

100

0 16 32 48 64 80 96

Weeks

%

0

20

40

60

80

100

0 16 32 48 64 80 96

Weeks

HIV-1 RNA > 500 copies/mL

HIV-1 RNA 50-500 copies/mL

HIV-1 RNA < 50 copies/mL

Discontinued LPV/r or EFV

LPV/r EFV

HIV-1 RNA level and discontinuation status, by visit, through 96 weeks

Cameron DW, JID 2008;198:234-40M03-613M03-613


-50

-25

0

25

50

75

100

-40 0 40 80 120

Lipoatrophy(p < 0.001)

Lipohypertrophy

LPV/r (N = 74)EFV (N = 32)

% c

han

ge

in l

imb

fat

at

wee

k 9

6

% change in trunk fat at week 96

Median percent change from baseline in limb fat and trunk fat

Scatter plot of percent change from baseline to W96 in limb fat vs trunk fat

-30

-20

-10

0

10

20

30

0 24 48 72 96

EFV limb fat

LPV/r trunk fat

EFV trunk fat

LPV/r limb fat

Weeks

*

* p < 0.001

*

Most common (frequency > 5%) moderate or severe adverse events related to treatment– LPV/r monotherapy group

• Diarhoea: 15%• Nausea: 14%

– EFV group• Asthenia: 12% • Dizziness: 12%• Insomnia: 12%• Rash: 10%• Depression: 6%

Most frequent grade 3 or 4 laboratory abnormalities– LPV/r monotherapy group

• Total cholesterol > 7.8 mmol/L: 12% ; Triglycerides > 8.5 mmol/L: 7%• Amylase > 2 ULN: 6%

– EFV group• Amylase > 5 ULN: 10%• ALAT > 5 ULN: 6%

Adverse events

Cameron DW, JID 2008;198:234-40M03-613M03-613


Conclusions– LPV/r monotherapy was less effective than EFV + ZDV/3TC

in maintaining virologic suppression: time to confirmed virologic rebound was shorter with LPV/r monotherapy

– Lipoatrophy was significantly lower in the LPV/r monotherapy group

Cameron DW, JID 2008;198:234-40M03-613M03-613


switch studies in virologically suppressed patients

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