The MONET trial 96 week analysis: darunavir/r monotherapy versus darunavir/r + 2NRTIs,
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The MONET trial 96 week analysis: darunavir/r monotherapy versus darunavir/r + 2NRTIs, for patients with HIV RNA < 50 copies/mL at baseline. Armin Rieger, Denes Banhegyi, Wolfgang Schmidt, Jose Arribas, Andrew Hill, Yvonne Van Delft, Christiane Moecklinghoff

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The MONET trial 96 week analysis: darunavir/r monotherapy versus darunavir/r + 2NRTIs, for patients with HIV RNA < 50 copies/mL at baseline

Armin Rieger, Denes Banhegyi, Wolfgang Schmidt, Jose Arribas, Andrew Hill, Yvonne Van Delft, Christiane Moecklinghoff

Presented at World AIDS Conference, Vienna, Austria, 22nd July 2010

Abstract TBLBB209


Monet trial design
MONET - Trial Design versus darunavir/r + 2NRTIs,

  • Inclusion: Taking 2 NRTI + either NNRTI or boosted PI at screening (stratified)

  • HIV RNA <50 copies/mL for at least 6 months, no prior use of darunavir (DRV)

  • No history of virological failure

DRV/r 800/100 mg OD

+ 2 NRTI (re-optimised at baseline)

n = 129

256 subjects

DRV/r 800/100 mg OD

n = 127

144 weeks

Primary Endpoint: failure at week 48 (TLOVR). Per Protocol, Switch = Failure

The Week 96 analysis was a secondary endpoint.

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet statistical methods for hiv rna analysis
MONET: statistical methods for HIV RNA analysis versus darunavir/r + 2NRTIs,

Main efficacy endpoint: TLOVR, switch equals failure analysis

If a patient shows a confirmed elevation in HIV RNA >50 copies/mL at two visits, this is a failure, even if the HIV RNA is then suppressed <50 copies/mL at Week 96.Stopping DRV/r in either arm, or adding NRTIs in the monotherapy arm is also a failure. Missing data is failure.

Secondary endpoint: Switch included analysis

This analysis only includes the HIV RNA levels at Week 96. If HIV RNA is re-suppressed at Week 96 following an earlier elevation, this is counted as success. Changes in treatment are permitted. Missing data is failure.

All results were consistent between the ITT and Per Protocol populations.

ITT analysis is shown here.

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet baseline characteristics itt
MONET: Baseline Characteristics (ITT) versus darunavir/r + 2NRTIs,

Age, years (median, range)

Male (%)

Caucasian (%)

43 (24-72)

83%

90%

43 (25-67)

78%

92%

579

12%

6.4 (4.0)

57%

43%

48%

28%

0

15 (12%)

12 (9%)

571

14%

7.4 (4.2)

56%

44%

35%

23%

0

24 (19%)

20 (16%)

Disease characteristics

CD4 count (median (range), cells/uL)

CD4 <350 cells/uL (%)

Duration of prior ARVs, years (mean, sd)

Use of PI at screening (%)

Use of NNRTI at screening (%)

On their first NRTI combination

PI naïve

Hep B Surface Antigen, positive, n (%)

Hep C Antibody, positive, n (%)

History of IV Drug use

DRV/r +2NRTI (n=129)

DRV/r

(n=127)

Multivariate analysis at Week 48 showed that HCV co-infection was highly predictive of response in the primary endpoint.

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet hiv rna by study visit observed data
MONET: HIV RNA by study visit (observed data) versus darunavir/r + 2NRTIs,

HIV RNA>50 copies/mL in 47/1051 samples (4.5%)

HIV RNA>50 copies/mL in 69/1009 samples (6.9%)

DRV/r + 2 NRTIs

DRV/r

>1000 copies/ml

400-1000 copies/ml

50-400 copies/ml

<50 copies/ml

n = 129 115 118 115 114 127 110 108 108 105

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet hiv rna 50 copies ml at week 96 tlovr switch failure itt population
MONET: HIV RNA <50 copies/mL at Week 96, TLOVR, Switch=failure (ITT population)

Switch=failure analysis (TLOVR) Switch included analysis

Difference = -5.8% (-16.0%, +4.4%)* Difference = +1.4% (-5.5%, +8.3%)*

100

92.1%

90.7%

90

80.6%

74.8%

80

HIV RNA

<50 by

Week 96

(%)

70

60

50

40

30

20

10

0

DRV/r + 2NRTI

DRV/r mono

DRV/r + 2NRTI

DRV/r mono

n=129

n=127

n=129

n=127

* 95% confidence intervals from univariate analysis

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet predictors of 96 week endpoint hiv rna 50 tlovr per protocol switch failure
MONET: Predictors of 96 week endpoint Switch=failure (ITT population)HIV RNA <50, TLOVR, Per Protocol, Switch=failure

Odds ratio (95% confidence intervals) for treatment failure (n.s.: not significant)

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


MONET trial: one patient in each treatment arm Switch=failure (ITT population)

with genotypic PI mutations during the trial

DRV/r + 2NRTI

Week 24 genotype shows M184V

+ PI mutations: I54V, V82T, L90M

Pre-screening genotype shows M184V

+ PI mutations: V82I, L90M

Week 12 genotype shows DRV RAM: L33F

DRV/r mono

No pre-screening genotype available

Both patient have HIV RNA <50 copies/mL on long-term follow up, with no change in treatment


Monet clinical adverse events
MONET: Clinical Adverse Events Switch=failure (ITT population)

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet week 96 conclusions
MONET Week 96: Conclusions Switch=failure (ITT population)

  • In the primary efficacy analysis at Week 96, rates of double HIV RNA blips and discontinuations were slightly higher in the DRV/r monotherapy arm, compared with the DRV/r + 2NRTI arm.

  • Most elevations in HIV RNA were low level (50-200 copies/mL), and patients were re-suppressed <50 copies/mL at Week 96, either on the original randomised treatment or with intensified treatment.

  • Non-inferiority was shown in the “Switch Included” analysis.

  • HCV co-infection and IV drug use were highly correlated with the primary endpoint.

  • There were no patients with phenotypic resistance to darunavir during the trial – one patient per arm showed at least one genotypic PI mutation.

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Acknowledgments thanks to the patients and investigators who participated in the trial
Acknowledgments – thanks to the patients and investigators who participated in the trial

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Thank you for your attention

Thank you for your attention! who participated in the trial


Monet grade 3 or 4 laboratory abnormalities
MONET: Grade 3 or 4 laboratory abnormalities who participated in the trial

  • * 3/5 rises in TCHOL in DRV/r + 2NRTI arm

  • * 6/14 rises in TCHOL in DRV/r mono arm were sustained

    Includes Grade 3 or 4 lab abnormalities recorded in at least 2 patients overall

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet hiv rna 50 copies ml at week 96 tlovr switch failure itt by hcv co infection at baseline
MONET: HIV RNA <50 copies/mL at Week 96, TLOVR, Switch=failure (ITT), by HCV co-infection at baseline

HCV Antibody negative at BL HCV Antibody positive at BL

n=217 n=39

HCV antibody positive patients

were 90% IV drug users, with

significantly worse adherence

3 double HIV RNA blips in DRV/r mono

arm at the time of acute HCV infection

100

90

85.9%

83.3%

80

73.3%

HIV RNA

<50 by

Week 96

(%)

70

60

50

43.5%

40

30

20

10

0

DRV/r + 2NRTI (PP)

DRV/r mono (PP)

DRV/r + 2NRTI (ITT)

DRV/r mono (ITT)

n=15

n=114

n=103

n=24

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


Monet hiv rna 50 copies ml at week 96 tlovr switch included itt by hcv co infection at baseline
MONET: HIV RNA <50 copies/mL at Week 96, TLOVR, Switch=included (ITT), by HCV co-infection at baseline

HCV Antibody negative HCV Antibody positive

n=217 n=39

95.1%

93.0%

100

90.4%

90

79.0%

80

HIV RNA

<50 by

Week 96

(%)

70

60

50

40

30

20

10

0

DRV/r + 2NRTI

DRV/r mono

DRV/r + 2NRTI

DRV/r mono

n=15

n=114

n=103

n=24

Rieger et al. WAC July 2010, Vienna [abstr TBLBB209]


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