None in DTG had genotypic or phenotypic emerging resistance DTG is NI to RAL The potential advantage of DTG (QD) versus RAL (BD) could not be assessed due to placebo-dosed randomization No emerging resistance on DTG SINGLE R, DB, NI → Superiority 48 weeks [32] 96 weeks [33] (OL after 96 weeks) R406 Funding: ViiV Healthcare

S: Canada, USA, selleck chemicals Australia, Europe D: black (24%); non-white (32%); males (84%); x = 35 years IC: ≥18 years, naïve to ART, VL >1,000 c/mL, screening for HLA-B*5701, a contraindication to ABC use R: DTG + ABC/3TC versus FTC/TDF/EFV stratified by VL ≤ or >100,000 c/mL and CD4 ≤ or >200 cells/mL 1°EP: VL <50 c/mL at week 48 Results: DTG demonstrated rapid viral suppression at 28 versus 84 days in the EFV arm (P < 0.0001). 1°EP: 88% SCH727965 DTG + ABC/3TC versus 81% FTC/TDF/EFV meeting NI, and

also superiority (P = 0.003, ITT) at 48 weeks and persisted to 96 weeks, 80% versus 72%, respectively (P = 0.006; 95% CI 2.3%, 13.8%). When stratified by VL >100,000 this difference was lost ABC/3TC/DTG is superior to FTC/TDF/EFV DTG statistically significant more rapid virologic decay compared to EFV No primary emerging resistance on DTG Flamingo [34] R, OL NI → Superiority Funding: ViiV Healthcare S: well-resourced countries D: non-white (28%); males 85%; x = 34 years; n = 484 IC: ≥18 years, naïve to ART, VL >1,000 c/mL OL: DTG 50 mg QD versus DRV/r 800 mg/100 mg QD with background either TDF/FTC or ABC/3TC. Stratified by VL ≤ or >100,000 c/mL (25% >100,000 c/mL) 1°EP: VL <50 c/mL at week 48 (NI margin −12%) Results: 48-week snapshot analysis showed 90 versus 83% had VL <50 c/mL. This demonstrated not only NI, but also S (P = 0.025; adjusted difference 7.1%; 95% CI 0.9–13.2). When stratified by those with VL >100,000 DTG superior to DRV/r 93% versus 70%, respectively. Fewer AE with DTG contributed to superiority. DTG had lower LDL values (2% versus 7%, these P < 0.001) and less diarrhea (17% versus 29%) DTG is

superior to DRV/r in treatment-naïve participants Phase 3 ART experienced SAILING [35] R, DB, NI Funding: ViiV Healthcare S: 1st to include RLSb Australia, Canada, Europe D: 68% male; 48% from RLS. 68% subtype B; 14% subtype C; 6% complex subtype. x = 43 years n = 715 participants IC: ART-experienced, INSTI-naïve; VL >400 c/mL × 2 consecutive or >1,000 c/mL at screening; resistance to ≥2 classes of ARV with 1–2 fully active drugs for OBR stratified by VL ≤ or >50,000 c/mL and DRV/r R: DTG 50 mg QD versus 400 mg RAL BD and investigator-selected OBR. 1°EP: HIV-1 RNA <50 c/mL at week 48. 2°EP: proportion of patients with tx-emergent INSTI resistance Results: 71% in DTG and 64% in RAL met 1°EP. Pre-specified statistical criteria revealed NI of DTG to RAL (adjusted treatment difference greater than −12%) and superiority (P = 0.03 mITT-E analysis; 95% CI >0).