ARV-trial.com Switch to DRV/r + RPV PROBE Study 1

PROBE Study: switch to DRV/r + RPV 118 Randomisation 1: 1 Open-label W48 Design Age ≥ 18 years HIV+ No previous resistance to study drugs HIV-1 RNA < 50 c/ml ≥ 6 months On stable (≥ 6 months) PI/r + 2 NRTI (TDF/FTC or ABC/3TC) HBs antigen negative N = 30 DRV/r 800/100 mg + RPV 25 mg qd Continuation of triple therapy N = 30 Objective Primary endpoint: proportion with HIV RNA < 50 c/mL at W24 and W48 (ITT, FDA snapshot) with non inferiority of DRV/r + RPV (lower limit of the 95% CI for the difference = -12%, 80% power) Protocol-defined virologic failure: 2 consecutive HIV RNA > 50 c/mL PROBE Maggiolo F. JAIDS 2016;72:46-51

PROBE Study: switch to DRV/r + RPV Baseline characteristics (mean) DRV/r + RPV N = 30 PI/r + 2 NRTI Age, years 49 48 Female 30% 10% cART, % TDF/FTC / ABC/3TC DRV/r / ATV/r NA 90 / 10 43 / 57 Current CD4/mm3 615 631 Pre-ART CD4/mm3 233 263 Pre-ART HIV RNA, copies/mL 272,000 215,000 Duration of current ART, months 38 Duration of HIV RNA < 50 c/mL, months 57 59 Baseline HIV DNA, copies/106 cells, median 15,200 10,900 PROBE Maggiolo F. JAIDS 2016;72:46-51

PROBE Study: switch to DRV/r + RPV 118 Virologic outcome at W24 and W48 (ITT, snapshot) DRV/r + RPV (N = 30) PI/r + 2 NRTI (N = 30) 100 80 60 40 20 W24 W48 HIV RNA < 50 c/ml HIV RNA > 50 c/ml No data in window % 7* 90.1 3 96.7 93.4 3** Favors Triple ART DRV/r + RPV W24 W48 -0.7 +20.7 +13.5 -7.5 -12 +12 Difference (95% CI) Virologic non inferiority at W24 and W48 * blips at 57 and 138 c/mL ** blip at 59 c/mL PROBE Maggiolo F. JAIDS 2016;72:46-51

PROBE Study: switch to DRV/r + RPV Secondary endpoints at W48 DRV/r + RPV PI/r + 2 NRTI Mean change in CD4/mm3 from baseline + 15 + 16 Mean change in CD8/mm3 from baseline - 21 - 41 Mean CD8+38+HLADR+ cell count at W48 3.4%* 5.2%* * p = 0.018 Safety and Tolerability at W48 DRV/r + RPV PI/r + 2 NRTI Severe adverse events, n Discontinuation for adverse event, n Grade 3-4 laboratory abnormalities, n Mean value of laboratory parameter Baseline W48 Total cholesterol, mg/dL 183 200 184 188 HDL-cholesterol, mg/dL 47 49 45 Triglycerides, mg/dL 173 128 143 eGFR, mL/min 101 100 99 95 Bone mineral density - - 0.0003 - 0.014 PROBE Maggiolo F. JAIDS 2016;72:46-51

PROBE Study: switch to DRV/r + RPV Conclusion A rilpivirine plus ritonavir-boosted DRV dual therapy was not inferior over 48 weeks to a standard boosted PI–based triple cART The dual therapy did not negatively affect lipid profile and renal function and was more friendly on bone mineral density This approach constitutes an alternative for patients experiencing nucleoside reverse transcriptase inhibitor–related toxicities Limitations Small sample size PROBE Maggiolo F. JAIDS 2016;72:46-51