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 292-0102: 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
N = 112 STR
> 18 years
ARV-naïve
HIV RNA > 5,000 c/mL
CD4 cell count > 50/mm3
eGFR > 70 mL/min
EVG/c/FTC/TDF placebo
N =58
EVG/c/FTC/TDF 150/150/200/300 mg
QD STR
EVG/c/FTC/TAF placebo
*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
2920102/TAF phase 2
Sax PE. JAIDS 2014;67:52-8
Study 292-0102: 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
2920102/TAF phase 2
Sax PE. JAIDS 2014;67:52-8
Study 292-0102: 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 < 0.001)
– Median change in eGFR by Cockcroft–Gault = -5.5 mL/min for E/c/F/TAF
vs -10.1 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
2920102/TAF phase 2
Sax PE. JAIDS 2014;67:52-8
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%
3%
Neutropenia
5%
2%
Amylase
3%
3%
Urine red blood cells
2%
0
Total cholesterol
2%
0
1% / 1%
2% / 0
Gamma glutamyl transferase
1%
2%
White blood cells
1%
0
Hypophosphatemia
1%
0
Urine protein
1%
0
Glucose
1%
2%
Triglycerides
1%
2%
ALT / AST
2920102/TAF phase 2
Sax PE. JAIDS 2014;67:52-8
Study 292-0102: 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
2920102/TAF phase 2
Sax PE. JAIDS 2014;67:52-8