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. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
ARV-trial.com
ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Design
Randomisation*
1 : 1
Open-label
W48
W96
N = 195
> 18 years
ARV-naïve
HIV RNA > 1,000 c/mL
Any CD4 cell count
HLA-B*5701 allele negative
ABC/3TC + EFV
N = 197
TDF/FTC + EFV
* Randomisation was stratified by screening eGFR (MDRD), race (black or non black), and BMI
Primary analysis
Intention to treat, exposed analysis : 2-sided significance level of 5%, with 90% power to detect a difference of 10 mL/min in eGFR (MDRD) change from baseline between arms
ASSERT
Post FA. JAIDS 2010;55:149-57 2

3. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
ARV-trial.com
ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Baseline characteristics and patient disposition
ABC/3TC + EFV
N = 192
TDF/FTC + EFV
N = 197
Median age, years 38 36
Female
17%
20%
Black
14%
16%
BMI (kg/m2) < 25 / > 25
66% / 33%
67% / 33%
eGFR (mL/min/1.73m2) < 90 / > 90
32% / 68%
33% / 67%
HIV RNA (log10 c/mL), median
5.01
5.12
CD4 cell count (/mm3), median
240
230
10-year coronary heart disease risk (Framingham score), median
2.97
2.90
Discontinuation by W48
63 (33%)
44 (23%)
For lack of efficacy
N =11
N = 2
For adverse event
N = 25
N = 20
Lost to follow-up
N = 5
Protocol deviation / Withdrew consent
N = 5 / N = 6
N = 1 / N = 4
Other reasons
N = 11
N = 12
ASSERT
Post FA. JAIDS 2010;55:149-57 3

4. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Adjusted mean change from baseline in eGFR by MDRD (ml/min/1.73 m2), ITT-e population
Repeated measures mixed model analysis
P = 0.435 -4 8 4
ABC/3TC + EFV
TDF/FTC + EFV
Change from BL in GFR by MDRD (ml/min/1.73 m²) -8 12 24 36 48
Treatment Difference
at week 48
Week
ABC/3TC EFV QD Better
TDF/FTC EFV QD Better
Treatment difference (ml/min/1.73 m²)
192
193
172
181
158
176
155
173
144
167
135
159
Subjects at visit
Mean change in eGFR
at week 96 :
(ABC/3TC)
(TDF/FTC)
ASSERT
Post FA. JAIDS 2010;55: ; Moyle GJ, Antiviral Therapy 2013;18:905-13

5. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Secondary renal endpoints
No differences between arms in proportion with significant declines in eGFR or with renal failure
Percentage change from baseline at week 48
Urinary retinol-binding protein/creatinine ratio : TDF/FTC = + 50% vs ABC/3TC = 0% (p < )
Urinary b2-microglobulin/creatinine ratio : TDF/FTC = + 24% vs ABC/3TC = - 47% (p < )
Changes in bone density (DXA) at week 48
ABC/3TC + EFV
TDF/FTC + EFV p
Mean change in total hip loss
- 1.9%
- 3.6%
< 0.001
Mean change in lumbar spine
- 1.6%
- 2.4%
0.036
BMD loss > 6% in the hip / in the spine
3% / 5%
13% / 10%
Bone turnover markers : increased in both groups over the first 24 weeks (significantly greater with TDF/FTC), stabilizing or decreasing thereafter
ASSERT
Post FA. JAIDS 2010;55: ; Moyle GJ, Antiviral Therapy 2013;18: ; Stellbrink HJ. CID 2010;51:963-72

6. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
ARV-trial.com
ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Efficacy at week 48 25 50
100 75
59.4
71.0
Adjusted difference
95% CI = 11.6% (2.2 ; 21.1)
ITT, TLOVR
ABC/3TC + EFV
TDF/FTC + EFV
HIV RNA < 50 c/mL %
Protocol-defined virologic failure (< 1 log10 c/mL reduction in HIV RNA by W4, confirmed rebound ≥ 400 c/mL after confirmed HIV RNA < 400 c/mL by W24 or confirmed HIV RNA > 400 c/mL after W24)
6 on ABC/3TC + EFV
Emergence of resistance : 3/6
2 patients with NNRTI mutations
1 patient with NNRTI mutation and K65R + D67N
2 on TDF/FTC + EFV = no resistance emergence
Median CD4/mm3 increase at W48 : in both groups
ASSERT
Post FA. JAIDS 2010;55:149-57 6

7. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
ARV-trial.com
ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Safety at W48
ABC/3TC + EFV
N = 192
TDF/FTC + EFV
N = 197
Drug-related adverse events
51%
47%
Grade 2-4
29%
20%
Most common grade 2-4 AEs : dizziness, abnormal dreams, drug hypersensitivity
Drug hypersensitivity
N = 12 (6%)
N = 1 (< 1%)
Clinically suspected ABC hypersensitivity
N = 6 -
Median changes in fasting lipids from baseline at W48
Total cholesterol, mg/dL
1.36
0.66
Triglycerides, mg/dL
0.23
0.05
LDL-cholesterol, mg/dL
0.81
0.39
HDL-cholesterol, mg/dL
0.38
0.28
Total cholesterol/HDL-cholesterol ratio
-0.934
ASSERT
Post FA. JAIDS 2010; 55:149-57 7

8. ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
ARV-trial.com
ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV
Conclusion
No difference in estimated glomerular filtration rate between ABC/3TC + EFV and TDF/FTC + EFV
However, increases in markers of tubular dysfunction in the TDF/FTC arm
No differences in markers of glomerular dysfunction over 96 weeks
Significant higher virologic efficacy for TDF/FTC + EFV
Emergence of resistance to NNRTI and NRTI on virological failure with ABC/3TC + EFV but not with TDF/FTC + EFV
Incidence of grade 4 adverse events and serious adverse events was higher in the ABC/3TC arm, mainly because of drug hypersensitivity or hypersensitivity
Smaller increases in serum lipids with TDF/FTC
Greater increases in bone turnover and decreases in hip and vertebral bone mineral density with TDF/FTC + EFV compared to ABC/3TC + EFV
ASSERT
Post FA. JAIDS 2010; 55: ; Moyle GJ, Antiviral Therapy 2013;18:905-13 8