Comparison of NNRTI vs NNRTI ARV-trial.com Comparison of NNRTI vs NNRTI ENCORE EFV vs RPV ECHO-THRIVE STAR EFV vs ETR SENSE DOR vs EFV DRIVE-AHEAD 1

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF Design Randomisation* 1 : 1 Double-blind W48 W96 > 18 years ARV-naïve HIV RNA > 1 000 c/mL Any CD4 cell count eGFR (CG) ≥ 50 mL/min No primary resistance to DOR, EFV, NRTI N = 364 DOR 100 mg/3TC/TDF QD + placebo EFV/FTC/TDF + placebo N = 364 * Randomisation was stratified by HIV RNA (< or > 100 000 c/mL) at screening and chronic hepatitis B or C DOR/3TC/TDF : 1 tablet qd as STR Objectives Non inferiority of DOR at W48: % HIV RNA < 50 c/mL by intention to treat, snapshot analysis (lower margin of the 95% CI for the difference = - 10%, 90% power) Superiority of DOR for neuropsychiatric adverse events by W48 DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF Baseline characteristics and patient disposition DOR/3TC/TDF (N = 364) EFV/FTC/TDF Median age, years 32 30 Female, % 16 15 AIDS, % 13 HIV RNA (log10 c/mL), mean 4.4 4.5 HIV RNA > 100 000 c/mL, % 20 23 CD4 cell count (/mm3), mean 435 416 CD4 < 200/mm3, % 12 Discontinuation at W48, N (%) Lack of efficacy, N Adverse event, N Death, N Lost to follow-up / Consent withdrawal, N Non-compliance / Other, N 51 (14%) 18 10 1 6 / 8 1 / 7 61 (17%) 10 23 3 7 / 11 2 / 5 DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF 58 Primary endpoint: HIV RNA < 50 c/mL at W48 (ITT, snapshot) 84 11 5 81 10 9 20 40 60 80 100 Virologic response non-response No data DOR/3TC/TDF (N = 364) % EFV DOR ‒ 10% + 10% 9.0 -2.0 3.5 Difference (95 % CI) EFV/FTC/TDF (N = 364) CD4 increase at W48 (ITT, NC = F) DOR: + 198/mm3 EFV: + 188/mm3 HIV RNA < 50 c/mL at W48 (observed failure approach) Baseline HIV RNA ≤ 100 000 c/mL: DOR: 90.6% vs EFV: 91.1 % Baseline HIV RNA > 100 000 c/mL: DOR: 81.2 % vs EFV: 80.8 % DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF 60 Protocol-defined virologic failures (PDVF) Definition Non response: HIV RNA ≥ 200 c/mL at W24 or W36 or confirmed HIV RNA ≥ 50 c/mL at W48 Rebound: confirmed HIV RNA ≥ 50 c/mL after obtaining HIV RNA < 50 c/mL DOR /3TC/TDF (N = 364) EFV/FTC/TDF Virologic failure, N 22 (6.0%) 14 (3.8%) Non response / Rebound 6 16 4 10 Discontinuations without PDVF, N 35 50 Genotype successfully performed, N Primary NNRTI resistance Primary NRTI resistance 23 6 * 5 * 24 12 ** 5 ** * NNRTI mutations : Y188L; V106I, F227C; V106V/I, H221H/Y, F227C; F227C; V106A, P225H, Y318Y/F; V106M/T, F227C/R ; NRTI mutations : M41L, M184V; M184V; M184V; K65R; K65K/R, M184V ** NNRTI mutations : K103N; K103N, E138E/G; K103N; G190E; K103N; K103N, M230L; G190E; K103N, V108V/I, T369T/A/I/V; K103N; K103N; K101K/N, K103N, P225P/H ; NRTI mutations : V118I, M184V; M184V; M184V; M184V, K219K/E; K65K/R, M184M/I DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF 62 Adverse events, % DOR/3TC/TDF (N = 364) EFV/FTC/TDF Drug-related adverse event 31 63 Serious adverse event 4 6 Discontinuation due to adverse event Drug-related 3 2 7 Discontinuation due to serious adverse event 1 < 1 Adverse event in ≥ 10% in either group Headache Diarrhea Nasopharyngitis Dizziness Nausea Abnormal dreams Rash 13 11 11 9 8 5 5 12 14 9 37 11 12 12 Grade 3-4 laboratory abnormalities Fasting LDL-cholesterol Fasting triglycerides Creatinine AST / ALT Lipase Creatine kinase < 1 / 1 2 3 1 1 / 1 1 3 DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF % with Predefined Neuropsychiatric Adverse Events at W48 DOR/3TC/TDF EFV/FTC/TDF 10 20 30 40 Dizziness Sleep disorders and disturbances Altered sensorium Depression and suicide/ self-injury Psychosis and psychotic disorders 8.8 37.1 12.1 25.5 4.4 8.2 4.1 6.6 0.3 1.1 p < 0.001 p = 0,033 % DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF Fasting Lipids (mg/dL): Change from Baseline at W48 -15 LDL-C p < 0,0001 Non-HDL-C Cholesterol Triglycerides HDL-C DOR/3TC/TDF EFV/FTC/TDF -10 -5 5 10 15 20 25 -1.6 8.7 -3.8 13.3 -2.0 21.8 -12.4 22.0 1.9 8.5 DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB

DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF ARV-trial.com DRIVE-AHEAD Study: DOR/3TC/TDF vs EFV/FTC/TDF Conclusion at week 48 In treatment-naïve adults with HIV-1 infection, DOR/3TC/TDF administered once daily demonstrated: Antiviral potency with non-inferior efficacy to EFV/FTC/TDF regardless of baseline HIV-1 RNA Low rate of resistance, with only 1.6% of participants developing resistance to any study drug through W48 DOR/3TC/TDF was generally well tolerated and safe: Neuropsychiatric profile superior to EFV/FTC/TDF, as measured by lower proportion of participants with neuropsychiatric adverse events in categories of dizziness, sleep disorders and disturbances, and altered sensorium Lipid profile superior to EFV/FTC/TDF, as assessed by difference from baseline in fasting LDL-C and non-HDL-C DRIVE-AHEAD Squires KE. IAS 2017, Abs. TUAB0104LB