Intensification with INSTI ARV-trial.com Intensification with INSTI REALITY 1

Adults, adolescents and children > 5 years ARV-trial.com REALITY Study: raltegravir-intensified quadruple therapy in first-line antiretroviral therapy Design Randomisation 1 : 1 Open label W48 N = 902 2 NRTI + NNRTI + 12 weeks of RAL Adults, adolescents and children > 5 years ARV-naïve CD4 < 100/mm3 N = 903 2 NRTI + NNRTI Two other factorial randomisations: 12 weeks enhanced prophylaxis, 12 weeks supplementary food Objective Primary endpoint: 24-week mortality REALITY Kityo C. AIDS 2016, Durban, Abs. FRAB0102LB 2

Baseline characteristics ARV-trial.com REALITY Study: raltegravir-intensified quadruple therapy in first-line antiretroviral therapy Baseline characteristics Additional RAL, N = 902 Standard ART, N = 903 Median age, years 5-17 years, % 36 4 Female, % 47 WHO stage 1 or 2, % 46 48 CD4 cell count (/mm3), median CD4 < 25/mm3, % 38 37 HIV RNA (log10 c/mL), median 230 660 230 000 HIV RNA > 100 000 c/mL, % 72 EFV, % 89 90 TDF/FTC backbone, % 78 80 REALITY Kityo C. AIDS 2016, Durban, Abs. FRAB0102LB 3

HIV RNA < 50 copies/mL (95% CI) REALITY Study: raltegravir-intensified quadruple therapy in first-line antiretroviral therapy Mortality HIV RNA < 50 copies/mL (95% CI) 902 825 801 786 775 766 657 903 830 789 776 760 669 10.2% 13.0% 10.9% 12.4% 5 10 15 20 N at risk 8 16 24 32 40 48 Weeks 60 80 100 4 12 14.5% 54.6% 76.0% 79.5% 42.8% 74.1% 77.2% 82.9% % Mean change in CD4/mm3 at W48: + 163 vs + 148 (p = 0.04) W24: HR =1.09 (95% CI: 0.82-1.46) ; p = 0.54 Additional RAL Standard ART REALITY Kityo C. AIDS 2016, Durban, Abs. FRAB0102LB

Secondary/other outcomes (HR, 95% CI) REALITY Study: raltegravir-intensified quadruple therapy in first-line antiretroviral therapy Secondary/other outcomes (HR, 95% CI) RAL better Standard ART better WHO 4 or death p = 0.72 WHO 3 or 4 or death p = 0.43 New TB disease p = 0.82 New cryptococcal disease p = 0.48 New candida disease p = 0.85 Presumptive severe bacterial infection p = 0.28 SAE p = 0.90 Grade 4 AE p = 0.28 Grade 3 or 4 AE p = 0.75 Grade 4 AE in first 12 weeks p = 0.86 Grade 4 AE related to ART p = 0.38 Grade 4 AE def/prob related to ART p = 0.03 AE leading to ART modification p = 0.51 0.5 0.7 1.0 1.5 2.0 REALITY Kityo C. AIDS 2016, Durban, Abs. FRAB0102LB

ARV-trial.com REALITY Study: raltegravir-intensified quadruple therapy in first-line antiretroviral therapy Conclusion Standard triple ART (FTC/TDF + EFV) intensified with raltegravir for 12 weeks Was well tolerated Resulted in faster HIV RNA reduction through 24 weeks, and higher increase in CD4 at 48 weeks But did not reduce mortality or WHO 3/4 events through either week 24 or 48 REALITY Kityo C. AIDS 2016, Durban, Abs. FRAB0102LB 6