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Switch to DRV/r monotherapy

The MONET study evaluates the non-inferiority of switching from a standard triple therapy to DRV/r monotherapy in HIV-positive patients. Results show non-inferior HIV RNA suppression at week 48. Consider DRV/r monotherapy for patients with sustained virologic suppression and no history of virologic failure.

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Switch to DRV/r monotherapy

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  1. Switch to DRV/r monotherapy • MONOI • MONET • PROTEA

  2. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy • Design Randomisation* 1 : 1 Open-label W48 W144 N = 129 293 HIV+ adults On 2 NRTIs + (PI or NNRTI) Darunavir-naïve No history of prior virologic failure HIV-1 RNA < 50 c/mL > 6 months N = 127 * Randomisation was stratified on the use of PI or NNRTI (57% patients on PI, 43% on NNRTI) ** NRTI used at baseline: TDF + FTC = 46% ; ABC + 3TC: 31% ; ZDV + 3TC = 10% ; TDF + 3TC = 7% ; other combinations: 6% • Objective • Non inferiority in the proportion of patients with HIV-1 RNA < 50 c/mL at W48 (per-protocol analysis, switch= failure, TLOVR algorithm) ; lower limit of the 95% CI for the difference= - 12%, 80% power Arribas J, AIDS 2010;24:223-230 MONET

  3. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy Baseline characteristics and patient disposition • At baseline, 13 patients had HIV-1 RNA levels > 50 c/mL (9 in the monotherapy arm and 4 in the triple therapy arm) despite having results < 50 c/ml at screening Arribas J, AIDS 2010;24:223-230 MONET

  4. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy HIV-1 RNA < 50 c/mL(TLOVR, switch = failure) ITT, switch-included analysis Per-protocol (primary endpoint) ITT % 95.1% 93.5% 87.8% 86.2% 85.3% 100 84.3% 75 50 25 N= 123 123 129 127 0 95% CI for the difference= - 10.1 ; 6.8 95% CI for the difference= - 9.9 ; 8.8 95% CI for the difference= - 7.4 ; 4.2 DRV/r + 2 NRTIs DRV/r qd monotherapy Results: W48 outcome • Non inferiority of DRV/r monotherapy Arribas J, AIDS 2010;24:223-230 MONET

  5. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy Outcomes of confirmed HIV RNA elevations Arribas J, AIDS 2010;24:223-230 MONET

  6. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy Outcomes of discontinuations from the trial Arribas J, AIDS 2010;24:223-230 MONET

  7. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy Other endpoints • In multivariate analysis, hepatitis C co-infection was a significant predictor of confirmed HIV RNA elevations (p < 0.01) • Resistance data: Genotype was available for 35/61 patients with HIV RNA > 50 c/mL (22 in the monotherapy group and 13 in the triple therapy group) • Resistance mutations to PI in 1 one patient in each arm, with no phenotypic resistance to DRV. HIV-1 RNA returned to < 50 c/mL without changing therapy in both patients • Most common grade 2 to 4 adverse events (AE) were gastrointestinal • Serious AE were seen in 9 patients in each group • Discontinuation for AE by W48 occurred in 8 patients in the monotherapy group and 3 in the triple therapy group • Grade 1 to 4 nervous system AE were seen in 16% of patients in each group, and Grade 1 to 4 psychiatric AE in 9% of patients in each group • There were more haematological abnormalities in the triple therapy arm,related to zidovudine Arribas J, AIDS 2010;24:223-230 MONET

  8. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy • Conclusions from W48 data • In patients with virologic suppression on standard triple therapy (2 NRTIs + 1 NNRTI or 1 PI), once-daily DRV/r monotherapy has shown non inferior HIV RNA suppression at week 48 compared with a standard therapy of 2 NRTIs + once-daily DRV/r • A switch to once-daily DRV/r monotherapy can be considered in patients who have HIV RNA < 50 c/mL for more than 6 months on other treatments and no history of virologic failure, but wish to avoid toxicities related to other ARVs Arribas J, AIDS 2010;24:223-230 MONET

  9. MONET Study: Switch PI or NNRTI to DRV/r qd monotherapy Results: W96 outcome • Monotherapy is not noninferior with switch = failure analysis at W96 • Δ-5.8% (95% CI: -16.0% to +4.4%) • If resuppression with intensification included as success, then monotherapy is noninferior at W96 • Δ +1.4% (95% CI: -5.5% to +8.3%) HIV-1 RNA < 50 c/mL at W96, ITT, TLOVR (%) DRV/r monotherapy (N = 127) DRV/r + 2 NRTIs (N = 129) 92.1 100 90.7 80.6 80 74.8 60 40 20 0 Switch = failure Switch allowed Rieger A, et al. AIDS 2010. Abs. THLBB209 MONET

  10. MONET Study: Switch PI or NNRTI to DRV/r qdmonotherapy HIV-1 RNA < 50 c/mL at W144 (ITT-TLOVR) Switch* = failure Switch* included • 2 consecutive HIV-1 RNA > 50 c/mL: • DRV/r monotherapy, N = 21 • DRV/r + 2 NRTI, N = 13 • 18/21 and 10/13 had HIV-1 RNA < 50 c/mL at W144 • Level of HIV-1 RNA at baseline and HCV co-infection were significantly associated with transient viremia during the 144 weeks (p < 0.05) • Resistance emergence to PI (IAS-USA): 1 in each arm, both before W24 Lower margin of the 95 % CI of the  - 16.9 % - 8.7 % % 83.5 % 84 % 100 75 % 69 % 75 50 25 0 DRV/r + 2 NRTI DRV/r mono DRV/r + 2 NRTI DRV/r mono Non inferiority of DRV/r monotherapy only in the « switch-included » analysis * Change in ARV MONET Arribas JR, HIV Medicine 2012;13:398-405

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