1. 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

2.  Design  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 ABC/3TC + EFV TDF/FTC + EFV Randomisation* 1 : 1 Open-label > 18 years ARV-naïve HIV RNA > 1,000 c/mL Any CD4 cell count HLA-B*5701 allele negative * Randomisation was stratified by screening eGFR (MDRD), race (black or non black), and BMI N = 197 N = 195 W48W96 ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010;55:149-57 ASSERT

3. ABC/3TC + EFV N = 192 TDF/FTC + EFV N = 197 Median age, years3836 Female17%20% Black14%16% BMI (kg/m 2 ) 2566% / 33%67% / 33% eGFR (mL/min/1.73m 2 ) 9032% / 68%33% / 67% HIV RNA (log 10 c/mL), median5.015.12 CD4 cell count (/mm 3 ), median240230 10-year coronary heart disease risk (Framingham score), median 2.972.90 Discontinuation by W4863 (33%)44 (23%) For lack of efficacyN =11N = 2 For adverse eventN = 25N = 20 Lost to follow-upN = 5 Protocol deviation / Withdrew consentN = 5 / N = 6N = 1 / N = 4 Other reasonsN = 11N = 12 Baseline characteristics and patient disposition ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010;55:149-57 ASSERT

4. Adjusted mean change from baseline in eGFR by MDRD (ml/min/1.73 m 2 ), ITT-e population Mean change in eGFR at week 96 : + 1.48 (ABC/3TC) - 1.15 (TDF/FTC) ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010;55:149-57 ; Moyle GJ, Antiviral Therapy 2013;18:905-13 ASSERT Repeated measures mixed model analysis P = 0.435 -4 0 8 4 ABC/3TC + EFV TDF/FTC + EFV Change from BL in GFR by MDRD (ml/min/1.73 m²) -8 -4 0 8 4 -8 0412243648 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 ABC/3TC + EFV TDF/FTC + EFV

5.  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 < 0.0001) Urinary  2-microglobulin/creatinine ratio : TDF/FTC = + 24% vs ABC/3TC = - 47% (p < 0.0001) ABC/3TC + EFVTDF/FTC + EFVp 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 spine3% / 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 Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010;55:149-57 ; Moyle GJ, Antiviral Therapy 2013;18:905-13 ; Stellbrink HJ. CID 2010;51:963-72 ASSERT Changes in bone density (DXA) at week 48

6. Efficacy at week 48 Median CD4/mm 3 increase at W48 : + 150 in both groups 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 % 0 Protocol-defined virologic failure ( 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 ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010;55:149-57 ASSERT

7.  Safety at W48 ABC/3TC + EFV N = 192 TDF/FTC + EFV N = 197 Drug-related adverse events51%47% Grade 2-429%20% Most common grade 2-4 AEs : dizziness, abnormal dreams, drug hypersensitivity Drug hypersensitivityN = 12 (6%)N = 1 (< 1%) Clinically suspected ABC hypersensitivityN = 6- Median changes in fasting lipids from baseline at W48 Total cholesterol, mg/dL 1.360.66 Triglycerides, mg/dL 0.230.05 LDL-cholesterol, mg/dL 0.810.39 HDL-cholesterol, mg/dL 0.380.28 Total cholesterol/HDL-cholesterol ratio - 0.559 -0.934 ASSERT Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010; 55:149-57 ASSERT

8.  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 Study: ABC/3TC + EFV vs TDF/FTC + EFV Post FA. JAIDS 2010; 55:149-57 ; Moyle GJ, Antiviral Therapy 2013;18:905-13 ASSERT