1. Comparison of NRTI combinations
ARV-trial.com
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 and GS-US 1

2. Study 292-0102: EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
ARV-trial.com
Study : EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
Design
Randomisation*
2 : 1
Double-blind
W24
W48
EVG/c/FTC/TAF 150/150/200/10 mg QD STR
EVG/c/FTC/TDF placebo
N = 112
> 18 years
ARV-naïve
HIV RNA > 5,000 c/mL
CD4 cell count > 50/mm3
eGFR > 70 mL/min
EVG/c/FTC/TDF 150/150/200/300 mg QD STR
EVG/c/FTC/TAF placebo
N =58
*Randomisation was stratified by HIV RNA (< or > 100,000 c/mL) at screening
Primary objective
Determine virologic efficacy of EVG/c/FTC/TAF
150 patients provide 76% power to detect a 1.5% (SD of 3.3%) difference in hip bone mineral density in the EVG/c/FTC/TAF arm relative to the EVG/c/FTC/TDF arm
/TAF phase 2
Sax PE. JAIDS 2014;67:52-8 2

3. Study 292-0102: EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
ARV-trial.com
Study : EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
Baseline characteristics
Median viral load at baseline : 4.6 log10 c/mL (21% > 100,000 c/mL), median CD4+ cell count : 391 cells/mm3 (15% > 200/mm3)
Main results
Discontinuation due to adverse events by W48 : 4 in TAF arm vs 0 in TDF arm
HIV RNA < 50 c/mL at W24 : 87.5% E/c/F/TAF vs 89.7% E/c/F/TDF
3 patients in each arm met criteria for resistance testing (virologic failure [2 consecutive HIV RNA > 50 c/mL] with HIV RNA > 400 c/mL). Genotype was performed on confirmatory sample
E/c/F/TAF : no resistance detected
E/c/F/TDF : 2 patients developed resistance, 1 to NRTI, 1 to INSTI + NRTI
PK substudy : plasma TFV exposure was 91% lower with E/c/F/TAF than with E/c/F/TDF, as measured by AUCtau. Conversely, intracellular TFV-DP levels in PBMCs were 5.3-fold higher with E/c/F/TAF
/TAF phase 2
Sax PE. JAIDS 2014;67:52-8 3

4. Study 292-0102: EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
ARV-trial.com
Study : EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
Safety
Significantly less change in the E/c/F/TAF arm in BMD at hip (-0.62% vs -2.39%, p < 0.001) and lumbar spine (-1.0% vs -3.37%, p < 0.001) at W48, which were also significant at week 24
In the E/c/F/TAF arm, 32% of patients had no decrease in hip BMD vs 7% in the E/c/F/TDF arm (p < )
Median change in eGFR by Cockcroft–Gault = -5.5 mL/min for E/c/F/TAF vs mL/min for E/c/F/TDF (p = 0.041)
Renal tubular proteinuria [urine retinol-binding protein/creatinine ratio and urine b-2 microglobulin/creatinine ratio] was significantly lower in patients who received E/c/F/TAF : no cases of proximal tubulopathy
Grade 3-4 adverse events : 9.8% TAF vs 5.2% TDF
Most common treatment-emergent adverse events : nausea (21% vs 12%), diarrhea (16% in each arm)
Higher elevations in lipids with TAF
/TAF phase 2
Sax PE. JAIDS 2014;67:52-8 4

5. Study 292-0102: EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
Grade 3 or 4 laboratory abnormalities
E/C/F/TAF
E/C/F/TDF
Any
25%
17%
LDL-cholesterol 9% 3%
Creatine phosphokinase 6%
Neutropenia 5% 2%
Amylase
Urine red blood cells
Total cholesterol
ALT / AST
1% / 1%
2% / 0
Gamma glutamyl transferase 1%
White blood cells
Hypophosphatemia
Urine protein
Glucose
Triglycerides
/TAF phase 2
Sax PE. JAIDS 2014;67:52-8

6. Study 292-0102: EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
ARV-trial.com
Study : EVG/c/FTC/TAF QD vs EVG/c/FTC/TDF QD (Phase 2)
Summary of week 48 results
In this phase 2, randomised clinical trial, HIV-positive treatment-naive adults received STRs of E/c/F/TAF or E/c/F/TDF. Both STRs demonstrated high and comparable rates of virologic suppression through 48 weeks of therapy
Both regimens were well tolerated, with few discontinuations due to adverse events. Nausea occurred more frequently with E/c/F/TAF
Plasma concentrations of TFV were substantially (91%) lower with E/c/F/TAF than with E/c/ F/TDF, and the TAF regimen delivered 5.3 times the intracellular, physiologically active metabolite, TFV-DP, to PBMCs, which could translate into less end-organ toxicity and/or improved virologic control
Significant smaller decreases in bone mineral density through 48 with E/c/F/TAF than with E/c/F/TDF
Urinary RBP/creatinine and b-2 microglobulin/creatinine ratios were significantly lower in the E/c/F/TAF arm, which suggests that TAF has a lesser effect than TDF on the proximal renal tubular cell
/TAF phase 2
Sax PE. JAIDS 2014;67:52-8 6