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Switch studies in virologically suppressed patients

Switch studies in virologically suppressed patients

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Switch studies in virologically suppressed patients

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  1. Switch studies in virologically suppressed patients Switch to TDF/FTC/EFV AI266-073 Switch to FTC + ddI + EFV ALIZE Switch to ATV/r-containing regimen ATAZIP Switch to ATV±r-containing regimen SWAN SLOAT Switch to ATV-containing regimen ARIES INDUMA Switch to ATV/r monotherapy ATARITMO Swedish Study ACTG A5201 OREY Synopsis • Switch to LPV/r monotherapy • Pilot LPV/r • M03-613 • American Study • KalMo • OK • OK04 • KALESOLO • MOST • HIV-NAT 077 • Switch to DRV/r monotherapy • MONOI • MONET • Switch to RAL-containing regimen • Canadian Study • CHEER • Montreal Study • EASIER • SWITCHMRK • SPIRAL

  2. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r • Design: 2 parallel trials, SWITCHMRK 1 and 2 Randomisation* 1 : 1 Double-blind W24 N = 350 HIV+ ≥ 18 years On LPV/r + ≥ 2 NRTIs HIV RNA < 50 c/mL (PCR) or < 75 c/mL (bDNA) > 3 months N = 352 * Randomisation was stratified on LPV/r use before entry (≤ 1 year vs > 1 year) • Primary endpoints • Mean percentage changes in fasting lipid concentrations from baseline to week 12 • Proportion of patients with HIV-1 RNA < 50 c/mL at week 24 • Frequency of adverse events up to week 24 Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  3. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r • Objectives • Lipids: 99% power to detect a between-treatment difference of 11%, 53% and 13% in the mean percentage change from baseline in total cholesterol, triglycerides, and non-HDL cholesterol, respectively, and 71% power to detect a between-treatment difference of 4% in the mean percentage change from baseline in LDL cholesterol • Viral load: non inferiority of RAL vs LPV/r: % HIV-1 RNA < 50 c/mLat week 24 (lower limit of the 95% CI for the difference = - 12%, 90% power) • Adverse events: for adverse events occurring in 20% of patients, each study had 80% power to declare with 95% confidence that the true difference between treatment groups was 12% or lower Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  4. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r Baseline characteristics and patient disposition Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  5. SWITCHMRK 1 10 0 1.3% 2.9% 8.2% 4% 2.1% 0.7% 2.3% 3.6% 0.8% 0.6% -0.9% -0.6% -2.4% -2.5% -10 p = 0.7 NT** p = 0.2 -12.8% -12.4% NT** -15.2% -14.8% -20 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 -30 -40 -41.5% -42.8% p < 0.0001 p < 0.0001 SWITCHMRK Study: Switch to RAL vs continuation of LPV/r Mean* % changes in fasting lipid concentrations from baseline to W12 SWITCHMRK 2 RAL + ARV LPV/r + ARV Mean(mmol/L) Total cholesterol NonHDL-C Triglycerides* LDL-C HDL-C Total cholesterol NonHDL-C Triglycerides* LDL-C HDL-C Baseline 5.6 5.3 4.3 4.1 2.1 1.8 3 2.7 1.3 1.2 5.6 5.5 4.3 4.2 2.4 2.5 2.7 2.7 1.2 1.2 W12 4.8 5.3 3.6 4.1 1.3 1.9 2.8 2.7 1.2 1.2 4.7 5.5 3.6 4.3 1.4 2.7 2.7 2.7 1.2 1.2 * median changes for triglycerides ** not tested Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  6. 93.8% 100 100 87.4% 90 90 80 80 88% 80.8% 70 70 (95% CI) : - 6.6 (-14.4 ; 1.2) (95% CI) : - 5.8 (-12.2 ; 0.2) 60 60 50 50 0 4 8 12 24 0 4 8 12 24 Weeks Weeks SWITCHMRK Study: Switch to RAL vs continuation of LPV/r Proportion of patients with HIV-1 RNA < 50 c/mL % % SWITCHMRK 1 SWITCHMRK 2 RAL + ARV LPV/r + ARV RAL + ARV 174 166 169 173 172 176 176 176 176 175 LPV/r + ARV 174 171 171 171 174 178 178 177 177 178 Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  7. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r Proportion of patients with HIV-1 RNA < 50 c/mL at W24* * Patients who did not complete the trial were regarded as failures Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  8. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r Grade 3 or 4 laboratory abnormalities Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  9. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r • Safety, resistance data • Similar frequency of clinical and laboratory events in both groups • No serious drug-related adverse event • Diarrhoea of moderate to severe intensity: 3% in LPV/r group vs 0%in RAL group • Discontinuation because of adverse events: 4 in LPV/r group vs 6in RAL group • 49 patients had confirmed virologic failure: • 32 in the RAL group: for 27 (84%), LPV/r was not their first ARV regimen and 18 (67%) of these patients had a history of virologic failure on previous regimens • 17 in the LPV/r group: for 8 (47%), LPV/r was not their first ARV regimen and 4 (50%) of these patients had a history of virologic failure on previous regimens • Raltegravir-associated resistance mutations were found at failure in 8/11 assessable patients Eron JJ, Lancet 2010;375:396-407 SWITCHMRK

  10. SWITCHMRK Study: Switch to RAL vs continuation of LPV/r • Conclusions • In patients with virologic suppression on a LPV/r-containing regimen, switching from LPV/r to RAL was associated, at W24, with: • Greater reductions in lipid concentrations than was continuationof LPV/r • Lower rate of HIV suppression, especially in patients who had a history of virologic failure before entry. Results did not establishnon inferiority of RAL to LPV/r • In the post-hoc analysis, patients without previous virologic failure had similar viral suppression rates in both treatment groups (switch to RAL or continuation of LPV/r) Eron JJ, Lancet 2010;375:396-407 SWITCHMRK