September 2016 IEEE 802.11 Closing Reports
This document provides a digest of the closing reports of various IEEE 802.11 sub-groups presented at the September 2016 closing plenary meeting. It includes attendance information, liaison reports, new members, and more.
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Switch to D/C/F/TAF EMERALD Study
EMERALD Study: Switch to D/C/F/TAF Design Randomisation * 2 : 1 Open label W48 W96 HIV+ 18 years On F/TDF + PI/r or/c 6 months Absence of history of virologic failure on DRV (previous VF allowed) Absence of DRV RAM (if historical genotype available) HIV RNA < 50 c/mL 2 months (1 blip 50-200 c/mL within past 12 months allowed) eGFR (Cockroft-Gault) 50 mL/min N = 763 D/C/F/TAF QD D/C/F/TAF Continuation PI/r or /C + F/TDF D/C/F/TAF N = 378 * Randomisation stratified by boosted PI Primary endpoint Proportion of patients with virologic rebound at W48 ; non-inferiority if lower margin of a two-sided 95% CI for the adjusted difference = - 4%, 89% power Virologic rebound: confirmed HIV RNA 50 c/mL (or single HIV RNA > 50 c/mL at W48), or premature discontinuation, irrespective of reason, with last HIV RNA 50 c/mL through W48 Orkin C. Lancet HIV. 2018; 5 :e23-34.; Eron J, IDWeek 2018, Abs. 1768 EMERALD
EMERALD Study: Switch to D/C/F/TAF Baseline characteristics and patient disposition D/C/F/TAF N = 763 46 18.3 75 / 20 / 5 630 41.6 59 15.2 104.2 Continuation PI/r or/C + F/TDF N = 378 45 17.2 75 / 22 / 4 624 42.6 57 14.1 103.3 Median age, years Female, % Race: white / black / other, % CD4/mm3, median On first ARV regimen, % Prior exposure to 5 ARV, % Prior virologic failure, % eGR (Cockroft-Gault), mL/min, median Boosted PI at screening, % DRV / ATV / LPV COBI Discontinuation by W48, N (%) For adverse event, N Withdrew consent, N Lost to follow-up, N Non-compliant, N Other reasons, N 70.8 / 21.5 / 7.7 14.0 34 (4.5) 11 10 5 2 6 70.4 / 21.7 / 7.9 17.2 20 (5.3) 8 5 0 0 3 Orkin C. Lancet HIV. 2018; 5 :e23-34. EMERALD
EMERALD Study: Switch to D/C/F/TAF Cumulative confirmed virologic rebound (HIV RNA 50 c/mL) through W48 Virologic response at W48 (HIV RNA < 50 c/mL), ITT snapshot % % 94.9 93.7 100 100 D/C/F/TAF (N = 763) Continuation PI (N = 378) 80 80 60 60 40 40 Difference : 0.4% (95% CI : - 1.5 to 2.2) 20 20 5.8 4.3 2.5 0.8 2.1 0.5 0 0 HIV RNA < 50 c/mL Difference : 1.2% (95 % CI : - 1.7 to 4.1) HIV RNA 50 c/mL No virologic data 4 patients with virologic rebound genotyped: 1 in D/C/F/TAF (presence of D67D/N) and 3 in continuation group (E138E/G NNRTI mutation in 1) Orkin C. Lancet HIV. 2018; 5 :e23-34 EMERALD
EMERALD Study: Switch to D/C/F/TAF Virologic rebound rate through W48 according to previous antiretroviral failure No previous ARV failure 1 previous ARV failure % % 100 100 D/C/F/TAF (N = 116) D/C/F/TAF (N = 647) Continuation PI (N = 53) Continuation PI (N = 325) 80 80 60 60 40 40 Difference: 0% (95% CI: - 2.6 to 2.0) Difference: 2.6% (95% CI: - 4.8 to 7.5) 20 20 2.5 2.5 2.6 0 0 0 Orkin C. Lancet HIV. 2018; 5 :e23-34. EMERALD
EMERALD Study: Switch to D/C/F/TAF Confirmed virologic rebound (HIV RNA 50 c/mL) HIV RNA < 50 c/mL at W96, ITT snapshot D/C/F/TAF immediate switch D0-W48 (N = 763) D/C/F/TAF immediate switch D0-W96 (N = 763) % % 94.9 100 100 90.7 80 80 60 60 40 40 20 20 3.1 2.5 0 0 Most rebounders (14/24 D/C/F/TAF immediate switch and 2/8 deferrred switch) resuppressed to HIV RNA < 50 c/mL by W96, without treatment change Genotype performed if virologic rebound 400 c/mL (4 D/C/F/TAF immediate switch and 5 deferred switch): no emergence resistance to NRTI or PI Eron J, IDWeek 2018, Abs. 1768
EMERALD Study: Switch to D/C/F/TAF Mean (SE) % change from baseline in bone mineral density (g/cm2) Continuation PI D/C/F/TAF Hip Lumbar spine 2 2 1.49 (3.34) 1.43 (2.34) 1 1 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 0 0 - 0.26 (2.00) - 0.63 (2.86) -1 -1 0 24 48 0 48 24 Weeks Weeks No of participants No of participants D/C/F/TAF Continuation PI 204 104 184 193 188 97 D/C/F/TAF Continuation PI 206 107 192 97 192 101 Lumbar BMD change at W48 D/C/F/TAF Continuation PI Hip BMD change at W48 D/C/F/TAF Continuation PI 31.8 8.9 3% 20.2 4.1 3% 15.1 1.0 5% 4.8 1.0 5% 7.8 19.8 3% 2.1 8.2 3% 1.6 8.9 5% 0 2.1 5% Orkin C. Lancet HIV. 2018; 5 :e23-34 EMERALD
EMERALD Study: Switch to D/C/F/TAF Mean (SE) % change from baseline in bone biomarkers Procollagen type N-terminal propeptide Alkaline phosphatase C-type collagen sequence N = 193 N = 191 N = 185 N = 103 N = 98 N = 98 5 5 20 0 0 10 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 p < 0.0001 -5 -10 0 p = 0.0003 -10 -10 -20 -15 -20 -30 -20 0 24 12 24 48 0 24 12 24 48 0 24 12 24 48 Weeks Weeks Weeks Parathyroid hormone N = 186 25-hydroxy vitamin D N = 96 N = 154 N = 76 20 D/C/F/TAF Continuation PI 30 15 10 20 p = 0.074 p = 0.0019 5 p = 0.495 p = 0.0074 10 0 0 -5 -5 -10 -10 0 24 48 0 24 48 Weeks Weeks Orkin C. Lancet HIV. 2018; 5 :e23-34. EMERALD
EMERALD Study: Switch to D/C/F/TAF Median lipid values TC:HDL-C ratio D/C/F/TAF baseline D/C/F/TAF W48 Continuation PI baseline Continuation PI W48 mmol/L mg/dL 205 * 5.2 3.84 ** 3.83.9 ** 200 181186 184 4 3.9 150 3 123129123128 123 * 103106 107 2.6 100 2 4750 * 48 47 1.3 50 1 0 0 0 * p < 0.0001 W48 vs baseline ; **p < 0.001 D/C/F/TAF vs continuation PI Orkin C. Lancet HIV. 2018; 5 :e23-34 EMERALD
EMERALD Study: Switch to D/C/F/TAF Mean Changes in eGFR (mL/min/1.73 m2) at W48 Between-group comparison p D/C/F/TAF Continuation PI eGFRcyst - 0.4 9.6 - 1.9 10.7 0.034 eGFR cr - 1.9 - 0.9 0.092 Orkin C. Lancet HIV. 2018; 5 :e23-34 EMERALD
EMERALD Study: Switch to D/C/F/TAF Adverse events between D0 and W48, % D/C/F/TAF (N = 763) PI/r or PI/C + F/TDF (N = 378) Grade 3-4 adverse event 7 8 Serious adverse event 5 5 Discontinuation for adverse event Due to renal event 1.4% (N = 11) 0.1% (N = 1 *) 1.3% (N = 5) 0.5% (N = 2 **) Adverse event in 5% of either group Naso-pharyngitis Upper respiratory tract infection Diarrhea Headache Back pain Vitamin D deficiency Osteopenia 11 11 8 8 7 7 5 10 10 4 4 6 7 6 Grade 3-4 laboratory abnormalities LDL-cholesterol 4,9 mmol/L Total-cholesterol 7.77 mmol/L Phosphate < 0,65 mmol/L Total bilirubin 2,6 x ULN 7 4 3 2 1 5 6 < 1 * Worsening of pre-existing renal insufficiency ; ** Toxic nephropathy, N = 1 ; tubulopathy, N = 1 Orkin C. Lancet HIV. 2018; 5 :e23-34 EMERALD
EMERALD Study: Switch to D/C/F/TAF Adverse events, D0-W96(%) D/C/F/TAF (N = 763) PI/b + F/TDF (N = 378) D/C/F/TAF (N = 352) D0-W48 D0-W96 D0-W52 W52-W96 Grade 3-4 adverse events 7.1 12.8 8.2 7.4 Serious adverse events 4.6 8.7 4.8 6.0 Discontinuation for adverse event 1.6 2.2 1.3 2.0 Deaths 0 0.4 * 0 0 * 1 metastatic pancreas cancer and 2 myocardial infarction Eron J, IDWeek 2018, Abs. 1768
EMERALD Study: Switch to D/C/F/TAF Changes in renal, lipid and bone parameters at W96 (%) PI/b + F/TDF (N = 378) D/C/F/TAF (N = 763) D/C/F/TAF (N = 352) D0-W96 D0-W52 W52-W96 Median change in eGDRCKD-EPI, mL/min/1,73 m2 UPCR UACR RBP:CR B2M:CR - 1.3 - 22.23 - 0.63 - 25.08 - 68.22 - 0.6 - 7.37 0.40 + 19.66 + 20.24 - 0.7 - 12.81 - 0.93 - 39.07 - 110.31 Median change in lipids, mg/dL Total cholesterol LDL-cholesterol HDL-cholesterol Triglycerides Total cholesterol/HDL-cholesterol ratio + 22.0 + 17.0 + 3.0 + 7.0 + 0.2 + 1.3 + 1.9 0 + 4.9 + 0.1 + 22.0 + 15.0 + 3.3 + 8.0 + 0.2 Mean % change in BMD Lumbar spine Total hip Femoral neck + 1.99 + 1.86 + 1.40 - 0.63 - 0.27 - 0.51 + 2.91 + 1.22 + 0.98 Eron J, IDWeek 2018, Abs. 1768
EMERALD Study: Switch to D/C/F/TAF Conclusion Through Week 96, switching from boosted PI + FTC/TDF to D/C/F/TAF resulted in: Low virologic rebound rate cumulative (2.5% at W48, 3.1 % at W96) High virologic suppression rate (94.9% at W48, 91% at W96) Virologic non-response rate of 1% No resistance to any study drug Few serious adverse events and discontinuations due to adverse events (2%) D/C/F/TAF bone, renal and lipid safety were consistent with known profiles of TAF and cobicistat Orkin C. Lancet HIV. 2018; 5 :e23-34; Eron J, IDWeek 2018, Abs. 1768 EMERALD
