The MONET trial: The MONET trial: darunavir/ritonavir monotherapy darunavir/ritonavir monotherapy shows non-inferior efficacy to shows non-inferior efficacy to standard HAART, for patients with standard HAART, for patients with HIV RNA <50 copies/mL at baseline HIV RNA <50 copies/mL at baseline JR Arribas, A Horban, J Gerstoft, G F JR Arribas, A Horban, J Gerstoft, G Fä tkenheuer, M Nelson, N Clumeck, tkenheuer, M Nelson, N Clumeck, F Pulido, A Hill, Y van Delft, C Moecklinghoff, T Stark for the MONET F Pulido, A Hill, Y van Delft, C Moecklinghoff, T Stark for the MONET Study Group Study Group Oral Late-Breaker presentation at 5th IAS Conference Oral Late-Breaker presentation at 5th IAS Conference Cape Town, South Africa, July 2009 Cape Town, South Africa, July 2009 #TUAB106-LB #TUAB106-LB
The MONET trial: darunavir/ritonavir monotherapy shows non-inferior efficacy to standard HAART, for patients with HIV RNA
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The MONET trial: darunavir/ritonavir The MONET trial: darunavir/ritonavir monotherapy shows non-inferior efficacy to monotherapy shows non-inferior efficacy to standard HAART, for patients with HIV RNA standard HAART, for patients with HIV RNA
<50 copies/mL at baseline<50 copies/mL at baselineJR Arribas, A Horban, J Gerstoft, G FJR Arribas, A Horban, J Gerstoft, G Fätkenheuer, M Nelson, N Clumeck, F Pulido, A Hill, tkenheuer, M Nelson, N Clumeck, F Pulido, A Hill, Y van Delft, C Moecklinghoff, T Stark for the MONET Study GroupY van Delft, C Moecklinghoff, T Stark for the MONET Study Group
Oral Late-Breaker presentation at 5th IAS ConferenceOral Late-Breaker presentation at 5th IAS ConferenceCape Town, South Africa, July 2009Cape Town, South Africa, July 2009 #TUAB106-LB#TUAB106-LB
MONET - Trial DesignMONET - Trial Design
• Taking 2 NRTI + either NNRTI or boosted PI at screening (stratified)
• No prior use of darunavir (DRV)
• HIV RNA <50 copies/mL for at least 6 months,
• No history of virological failure
4, 12, 24, 36, 48 weeks96 wks
Primary Endpoint: HIV RNA< 50 at week 48 (TLOVR). Per Protocol, Switch = Failure• 2 consecutive HIV RNA > 50 copies/mL (Roche Amplicor HIV-1 Monitor assay 1.5)• Stopping DRV/r • Starting NRTIs in the monotherapy arm• Stopping NRTIs in the triple therapy arm (switches in NRTIs were permitted at any time).
Follow-upphase 96 weeks
256 subjects
DRV/r 800/100 mg OD+ 2 NRTI (re-optimised at baseline)
n = 129
DRV/r 800/100 mg ODn = 127
Follow-upphase 96 weeks
No run-in period
SC
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
30 days BL
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
MONET: Study Design and ObjectivesMONET: Study Design and Objectives
• Primary objective: to show non-inferior efficacy for DRV/r monotherapy (800/100 mg OD dose) versus standard HAART (DRV/r + 2 NRTI).
• Study power: 80% to show non-inferiority for DRV/r vs DRV/r + 2 NRTIs, with a sample size of 125 patients per arm (delta = -12%).
• Analysis:− Per protocol (PP): excluded patients with major protocol
violations such as a history of virological failure, or patients randomised incorrectly (n = 10).
Time to loss of virolgical response (TLOVR)
− Observed: only virological endpoints.− Intent To Treat (ITT) – all randomised patients▫ Switch = Failure (S = F)▫ Switch Included (S F)
• All patients were followed up to Week 48
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
Disease characteristics CD4 count (median, 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 (%)
MONET: Primary Efficacy Analysis:MONET: Primary Efficacy Analysis:HIV RNA <50 copies/mL at Week 48, TLOVR, S = F HIV RNA <50 copies/mL at Week 48, TLOVR, S = F
Table EFF 4-5
HIV RNA<50 byWeek 48(%)
Per Protocol analysis (PP) Intent to Treat analysis (ITT)Primary analysis
non-inferior efficacy versus triple antiretroviral drug treatment at Week 48.
Most elevations in HIV RNA were low level (50-400 copies/mL), and patients were re-suppressed <50 copies/mL at last visit, either on the original randomised treatment or with intensified treatment.
There were no patients with phenotypic resistance to darunavir during the trial – one patient per arm showed at least one genotypic PI mutation.
No new or unexpected safety signals were detected (details submitted to EACS and AELD conferences).
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
Efficacy of darunavir/ritonavir as single-drug Efficacy of darunavir/ritonavir as single-drug maintenance therapy in patients with HIV-1 maintenance therapy in patients with HIV-1 viral suppression: a randomized open-label viral suppression: a randomized open-label
C. Katlama et al #WELBB102C. Katlama et al #WELBB102
WEDNESDAY. LATE BREAKERS TRACK B. WEDNESDAY. LATE BREAKERS TRACK B. Session Room 1. 13:10Session Room 1. 13:10
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
Country and Race
Israel3.1%
Hungary4.3%
Germany10.9%
Denmark10.9%
Belgium9.4%
Austria6.3%
UK8.2%
Switzerland0.8%
Spain18.8%
Russia4.3%
Portugal5.5%
Poland11.3% Italy
6.3%
MONET: AcknowledgementsMONET: Acknowledgements
Thanks to all the 256 patients who participated in the MONET trial, plus the investigators and study monitors
J. Arribas et al, IAS Conference, Cape Town, SA, 21 July 2009, TUAB106-LB
MONET: AcknowledgementsMONET: Acknowledgements
Participating centers:Austria: A. Rieger, N. VetterBelgium: N. Clumeck, E. FlorenceSwitzerland: P. VernazzaGermany: G. Fätkenheuer, A. Stoehr, W. Schmidt, M, Stoll, C. StephanDenmark: J. Gerstoft, C. Pedersen, L. MathiesenSpain: B. Clotet, F. Pulido, J. Arribas, J. Gatell, J. Iribarren, R. Rubio, J. PasquauUnited Kingdom: M. Johnson, B. Peters, M. Nelson, A. Winston, Hungary: D. BanhegyiIsrael: S. MaayanItaly: A. Lazzarin, A. Antinori, F. Suter, A. D‘Arminio Monforte, G. CarosiPoland: A. HorbanPortugal: F. Antunes, R. MarquesRussia: N Zakharova, V. Pokrovsky
The authors would like to thank the patients and their families for their participation and support during the study, and the MONET study team and co-investigators for their collaboration.
This study was sponsored by Tibotec, a division of Janssen-Cilag.