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Tenofovir/FTC+Efavirenz Compared to Combivir+Efavrienz, Safety & Efficacy at 96 Weeks. 934 Study
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Reported by Jules Levin
8th International Congress on Drug Therapy in HIV Infection
November 12-16, 2006, Glasgow, UK
"Efficacy and Safety of Tenofovir DF (TDF), Emtricitabine (FTC) and Efavirenz (EFV) Compared to Fixed Dose Zidovudine/Lamivudine (CBV) and EFV Through 96 Weeks in Antiretroviral Treatment-Naïve Patients. Study 934"
AL Pozniak,1 JE Gallant,2 E DeJesus,3 JR Arribas,4 R Campo,5 S-S Chen,6
D McColl,6 J Enejosa,6 and AK Cheng6 for the Study 934 Team
1Chelsea and Westminster Hospital, London, UK; 2Johns Hopkins University School of Medicine, Baltimore, MD, USA;
3Orlando Immunology Center, Altamonte Springs, FL, USA; 4University Hospital La Paz, Madrid, Spain;
5University of Miami, Miami, FL, USA; 6Gilead Sciences, Inc., Foster City, CA, USA
This is a large phase III trial comparing once daily TDF, FTC and efavirenz (EFV) to twice daily CBV (AZT+3TC) and once daily EFV.
At Week 48, the proportion of patients reaching primary endpoint of HIV RNA < 400 c/mL using the FDA TLOVR algorithm was significantly higher in the TDF+FTC+EFV arm1
This presentation provides the results of Week 96 data analysis.
1. Gallant JE, DeJesus E, Arribas JR, et al. Tenofovir DF, emtricitabine and efavirenz vs. zidovudine, lamivudine and efavirenz for HIV. N Engl J Med 2006; 354:251-60.
AUTHOR CONCLUSIONS
The TDF+FTC+EFV arm was associated with significantly greater virologic suppression to HIV RNA < 400 c/mL and a greater increase in CD4 cell
count
Renal function remained stable through 96 weeks. No patient discontinued due to renal adverse events.
Significantly less M184V/I was seen in the TDF+FTC+EFV arm
No emergence of K65R mutation was demonstrated
Signifcantly higher limb fat was seen in TDF+FTC+EFV arm compared to CBV+EFV arm
- In a subset of patients with Week 48 and 96 data, a significant median decrease in limb fat was seen in the CBV+EFV arm and a significant increase in the TDF+FTC+EFV arm
BRIEF SUMMARY:
-- % <400 c/ml: 75% TDF/FTC, 62% CBV (p=0.004; 95% CI: +4.3%, +21.1%)
-- % <50 c/ml: 67% TDF/FTC, 61% CBV (p=0.16; 95% CI: -2.3%, +15.0%)
-- CD4 Increase: +270 in TDF/FTC, +237 CBV (p=0.036)
-- Resistance development: 2 M184V in TDF./FTC, 9 in CBV (p=0.036), no K65R
-- Adverse events: 5% TDF/FTC, 11% CBV (p=0.008); anemia: 0 TDF/FTC, 6% CBV.
-- Weight gain: +4.1 kg in TDF/FTC, +1.0 kg in CBV (p<0.001)
-- Renal: serum creatinine: 0 grade 1-4 in TDF/FTC, 2 grade 1 or 2 in CBV. Cockroft-Gault (median changes): TDF/FTC 121 at baseline, 119 at week 96; CBV 121 at baseline, 118 at week 96. MDRD (median changes): at week 96-- 108 for CBV, 100 for TDF/FTC (p=0.006); change from baseline: TDF/FTC, from 110 to 100; CBV: 105 at baseline to 108 at wk 96.
-- Limb fat: there was no baseline measure. At week 48: 6.0 kg for CBV, 7.4 for TDF/FTC (p=0.034); at week 96: 5.5 kg for CBV, 8.1 for TDf/FTC. Changes from week 48 to week 96 were statistically significant.
Figure 1. Study Design
517 ART-naïve patients in Europe & USA randomized 1:1 to TDF+FTC+Efavirenz, all once daily (QD) or AZT/3TC (Combivir) twice daily (bid) + Efavirenz QD, once daily, for 144 weeks. Adequate renal & hepatic function at baseline. FTC/TDF Fixed Dose Combination tablet used after week 96.
Statistical Analysis
- Non-inferiority trial with 48 week primary endpoint
- Efficacy endpoint: Time to Loss of Virologic Response (TLOVR)
- Similar to ITT Missing = Failure, Switch = Failure (switching EFV to NVP due to CNS toxicity was not considered failure)
- Requires confirmation for success
- FDA-required endpoint for presentation in U.S. Prescribing Information of newly approved antiretrovirals
- Week 96 Efficacy Patients:
- Patients with baseline NNRTI-R mutations and patients who completed the Week 48 study with HIV RNA below limit of quantification but did not consent to participate in the study extension from Weeks 48 - 96 were excluded from the analysis
RESULTS
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