CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

Results: 1024 pts were randomized and exposed (DTG+RPV 513; CAR 511), across both studies. Switching to DTG+RPV was non-inferior to continuing CAR at Wk48 for VL<50c/ mL in pooled analysis of both the ITTe population [95% vs. 95%; difference: -0.4% (95% CI: -3.1%, 2.3%)] and the per-protocol population [96% vs. 96%; difference: 0.7% (95% CI: -3.3%, 1.8%)]. Efficacy results for SWORD-1 (VL<50c/mL in ITTe [95% vs. 96%; difference: -0.6% (95% CI: -4.3%, 3.0%)]) and SWORD-2 (VL<50c/mL in ITTe [94% vs. 95%; difference: -0.2% (95% CI: -4.2%, 3.8%)]) were comparable. Low rates of snapshot virologic failures (VFs) at Wk48 were observed for both studies (Table 1). One pt on DTG+RPV with protocol defined VF had an NNRTI RAM (K101K/E); no pts had any INI RAMs. More adverse events (AEs) were reported and led to discontinuation in the DTG+RPV arm; no unexpected AEs were identified for either drug. Conclusion: A switch to a novel, once daily 2DR of DTG+RPV demonstrated high efficacy and was non-inferior to the continuation of CAR in virologically suppressed HIV-1- infected adults. The safety profiles of both DTG and RPV were consistent with the respective labels. A DTG+RPV 2DR offers the potential for reduction in cumulative ART exposure, without an increased risk of virologic failure.

Oral Abstracts

45LB DORAVIRINE IS NON-INFERIOR TO DARUNAVIR/R IN PHASE 3 TREATMENT-NAÏVE TRIAL AT WEEK 48 Jean-Michel Molina 1 , Kathleen Squires 2 , Paul E. Sax 3 , Pedro Cahn 4 , Johan Lombaard 5 , Edwin DeJesus 6 , Xia Xu 7 , Bach-Yen T. Nguyen 7 , George Hanna 7 , Carey Hwang 7 1 Hôpital St Louis, Paris, France, 2 Thomas Jefferson University, Philadelphia, PA, USA, 3 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, 4 Fundación Huesped, Buenos Aires, Argentina, 5 Josha Research, Bloemfontein, South Africa, 6 Orlando Immunology Center, Orlando, FL, USA, 7 Merck & Co., Inc., Kenilworth, NJ, USA Background: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with once-daily dosing and potent in vitro activity against the most common NNRTI resistant variants (K103N, Y181C, G190A). In a phase 2b study, DOR 100 mg once daily (QD) demonstrated similar efficacy to efavirenz, with favorable safety and tolerability through Week 48. Methods: DRIVE-FORWARD is an ongoing, phase 3, multicenter, double-blind, non-inferiority trial in antiretroviral treatment-naïve adults with HIV-1 infection and pre-treatment HIV-1 RNA ≥1,000 c/mL. Participants were stratified by screening HIV-1 RNA (≤ or >100,000 c/mL) and investigator-selected NRTI backbone therapy (TDF/FTC or ABC/3TC) and randomized in a 1:1 ratio to receive DOR 100 mg QD or darunavir 800 mg with ritonavir 100 mg (DRV/r) QD, in combination with the selected NRTI, for up to 96 weeks. The primary endpoint was the proportion (%) of participants achieving HIV-1 RNA <50 c/mL at Week 48 (NC=F, FDA Snapshot approach) with predefined non-inferiority margin of 10%. A secondary objective was to evaluate the effects of DOR and DRV/r on fasting serum lipids. Results: Of 769 participants randomized, 766 (383 in each group) received study drug and were included in the efficacy and safety analyses (mean age 35.2 years, 84%male, 73% white, 87% on TDF/FTC). DOR was non-inferior to DRV/r on the primary endpoint, with 83.8% (321/383) and 79.9% (306/383), respectively, achieving HIV-1 RNA <50 c/mL at Week 48 (difference 3.9%, 95% CI [-1.6, 9.4]). In the subgroup with baseline HIV-1 RNA >100,000 c/mL, 81.0% (64/79) on DOR and 76.4% (55/72) on DRV/r achieved HIV-1 RNA <50 c/mL at Week 48 (OF approach). Adverse event rates (overall, serious, drug-related, and leading to treatment discontinuation) were similar across treatment groups (see table). The most common drug-related AEs (>5% in one or more treatment groups) were diarrhea (5.5%, 12.8%), nausea (6.5%, 7.6%), and headache (6.0%, 2.6%) for DOR and DRV/r, respectively. Fasting LDL-C and non-HDL-C were reduced by DOR and increased by DRV/r (see table) with statistically significant treatment differences (p<0.0001). Conclusion: At Week 48, DOR demonstrated potent efficacy and was non-inferior to DRV/r on a background of 2 NRTIs in HIV-1 treatment-naïve adults. Efficacy was similar regardless of baseline HIV-1 RNA. DOR was generally safe and well-tolerated with a superior lipid profile for fasting LDL-C and non-HDL-C compared to DRV/r.

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CROI 2017