Comparison of NRTI Combinations ZDV/3TC vs TDF + FTC Studies
Explore the comparison of NRTI combinations ZDV/3TC vs TDF + FTC in various studies including Study 934, HEAT Study, ACTG A5202 Study, ASSERT Study, and FTC/TDF vs FTC/TAF Studies. The studies analyze the efficacy, safety, and tolerability of different NRTI combinations in HIV treatment.
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Comparison of NRTI combinations ZDV/3TC vs TDF + FTC Study 934 ABC/3TC vs TDF/FTC HEAT Study ACTG A5202 Study ASSERT Study FTC/TDF vs FTC/TAF Studies GS-US-292-0104 and GS-US-292-0111
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Design Randomisation* 1 : 1 Open-label W48 W144 TDF 300 mg QD N = 255 FTC 200 mg QD 517 ARV-na ve patients > 18 years HIV RNA > 10,000 c/mL Any CD4 cell count EFV 600 mg QD N = 254 ZDV/3TC 300/150 mg BID EFV 600 mg QD *Randomisation was stratified on CD4 cell count < 200 or > 200/mm3 Objective Non inferiority of TDF + FTC + EFV vs ZDV/3TC + EFV at W48: % HIV RNA < 400 c/mL, TLOVR algorithm (lower margin of the 95% CI for the difference = -13%, 85% power) Gallant JE. NEJM 2006;354:251-60 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Baseline characteristics TDF + FTC ZDV/3TC fdc Randomized, N 258 259 Treated eligible patients, N 255 254 Median age, years 36 37 Female 14% 13% White/Black/Other 56% / 25% / 19% 61% / 20% / 19% HIV RNA (log10c/mL), median HIV RNA > 100,000 c/mL 5.0 5.0 52% 50% CD4 cell count (/mm3), median 233 241 CD4 < 200/mm3 42% 41% CD4 < 50/mm3 15% 11% Baseline NNRTI resistance mutations, N * Excluded from primary endpoint analysis 11* 11* Note : TDF, FTC and EFV taken without regards to meals and preferably at bed time; Substitution of NVP for EFV allowed if EFV intolerance; not considered as treatment failure Gallant JE. NEJM 2006;354:251-60 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Response to treatment at week 48 Primary endpoint % 100 /mm3 200 TDF + FTC ZDV/3TC 190 84 80 158 77 80 160 73 70 68 60 120 40 80 20 40 N = 244 243 244 243 255 254 0 0 HIV RNA < 400 c/mL TLOVR HIV RNA < 50 c/mL TLOVR HIV RNA < 50 c/mL ITT Mean CD4 increase (p = 0.002) 95% CI for the difference = 4; 19 (p = 0.002) 95% CI for the difference = 2; 17 (p = 0.02) 95% CI for the difference = 1; 16 (p = 0.03) Gallant JE. NEJM 2006;354:251-60 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Safety and tolerability: TDF + FTC vs ZDV/3TC Similar frequency of clinical adverse events grade 2 to 4 and laboratory abnormalities grade 2 to 4 in both groups, respectively 63% vs 63% and 56% vs 57% Significantly more discontinuations for adverse events in the ZDV/3TC group: 9% vs 4% (p = 0.02); mainly for anemia (N = 14 vs 0) Renal safety was similar in both groups and no patients discontinued because of renal events. Change in median GFR (MDRD) at W48 was similar in both groups (< - 1 mL/min/1.73 m2). No Fanconi s syndrome occurred Mean increase significantly lower in the TDF + FTC group for total cholesterol, LDL-cholesterol and HDL-cholesterol; increase in triglycerides modest and not different between groups At week 48, DEXA substudy in 100 patients (no baseline evaluation): significantly less total limb fat with ZDV/3TC (mean 6.9 vs 8.9 kg; p = 0.03) Gallant JE. NEJM 2006;354:251-60 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Resistance data Genotypic analysis was done in patients without baseline NNRTI resistance if 1)viral rebound (2 consecutive HIV RNA > 400 c/mL after achieving < 400 c/mL 2)HIV RNA > 400 c/mL at W48 3)discontinuation before W48 with HIV RNA > 400 c/mL at the last visit Patients with baseline resistance (11 in each group) were excluded from this analysis of resistance TDF + FTC N = 244 ZDV/3TC N = 243 Patients in genotypic analysis 12 23 * Wild-type 3 5 Any resistance mutation 9 17 K65R 0 0 M184V/I 2 7 TAM 0 1 EFV resistance mutation ** 9 16 EFV resistance mutation + M184V * 1 technical failure; ** K103N mutation developed in 21 of 25 patients 2 6 Gallant JE. NEJM 2006;354:251-60 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Study extended to 3 years of follow-up (W144) At week 96, patients on TDF + FTC swithed to fixed-dose combination TDF/FTC Results at week 144 TDF/FTC ZDV/3TC p HIV RNA < 400 c/mL 71% 58% 0.004 HIV RNA < 50 c/mL 64% 56% 0.08 CD4 increase (/mm3) 312 271 0.09 Discontinuation for virologic failure 2% 6% 0.038 Discontinuation for adverse events* 5% 11% 0.01 Median GFR (MDRD) W144 minus baseline (mL/min/1.73m2) - 12 + 1 < 0.001 Mean total limb fat (DEXA) 7.9 kg 5.4 kg < 0.001 * No discontinuation for renal events Arribas JR. JAIDS 2008;47:74-8 Study 934
Study 934: zidovudine/lamivudine fixed dose combination vs tenofovir + emtricitabine Conclusions TDF + FTC + EFV is non inferior to ZDV/3TC + EFV Greater virologic response rates to TDF + FTC + EFV as compared with ZDV/3TC + EFV Significantly greater CD4 response with TDF + FTC Greater tolerability of TDF + FTC This study shows superior outcome in the tenofovir-emtricitabine group At week 144, TDF/FTC + EFV demonstrates superior durability of viral load suppression and an improved safety and morphologic profile compared with ZDV/3TC and EFV Gallant JE. NEJM 2006;354:251-60; Arribas JR. JAIDS 2008;47:74-8 Study 934
