Nuovi paradigmi della HAART Antonella Castagna IRCCS San Raffaele Nuove associazioni terapeutiche in HIV, tra efficacia e sostenibilita Catania, 9 novembre 2015

clinicaloptions.com/hiv Highlights of IAS 2015 START: Immediate vs Deferred Therapy for Asymptomatic, ART-Naive Pts  International, randomized trial  Composite primary endpoint: time to any serious AIDS-related (AIDS-related death or AIDS-defining event) or non-AIDS–related event (non-AIDS–related death, CVD, end- stage renal disease, decompensated liver disease, non-AIDS–defining cancer)  By May , approximately 60% of the planned 213 primary events had occurred. Immediate ART ART initiated immediately following randomization (n = 2326) INSIGHT START Study Group. N Engl J Med. 2015;[Epub ahead of print]. Lundgren J, et al. IAS Abstract MOSY0302. Deferred ART Deferred until CD4+ cell count ≤ 350 cells/mm 3, AIDS, or event requiring ART (n = 2359) HIV-positive, ART-naive adults with CD4+ cell count > 500 cells/mm 3 (N = 4685) Study closed by DSMB following interim analysis

P<0,001P=0,04 P=0,13 P=0,25

Jun 2015 Report

DHHS Guidelines 2012: Preferred Regimens for ARV naive patients DHHS Guidelines 2015: Preferred Regimens for ARV naive patients Class Regimen INSTI-basedRaltegravir + Tenofovir-Emtricitabine (AI) NNRTI-basedEfavirenz-Tenofovir-Emtricitabine (AI) PI-basedAtazanavir + Ritonavir + Tenofovir-Emtricitabine (AI) Darunavir (qd) + Ritonavir + Tenofovir-Emtricitabine (AI) Class Regimen INSTI-basedRaltegravir + Tenofovir-Emtricitabine (AI) Dolutegravir/Abacavir/Lamivudine a (AI) Dolutegravir + Tenofovir-Emtricitabine (AI) Elvitegravir/cobi/Tenofovir/Emtricitabine b (AI) PI-basedDarunavir (qd) + Ritonavir + Tenofovir-Emtricitabine (AI) a. only for patients who are HLA-B*5701 negative b. only for patients with pre-treatment estimated CrCl ≥70 mL/min

AMBER: D/C/F/TAF FDC in Naïves A Phase 3, Randomized, Active-controlled, Double Blind, Non-inferiority Study Primary Outcome Measures: Percentage of Participants With HIV-1 RNA< 50 copies/mL defined by FDA Snapshot Approach at Week 48 DRV/cobi+FTC/TDF* +matched placebo Estimated Enrollment:670 untill March 2016 Study Start Date:July 2015 Estimated Study Completion Date:September 2018 Estimated Primary Completion Date:April 2017 (Final data collection date for primary outcome measure) D/C/F/TAF** FDC QD + matched placebos HIV-1 >=18 years ART-naïve Plasma HIV-1 RNA ≥ 1,000 c/mL at Screening randomised D/C/F/TAF** FDC QD D/C/F/TAF** FDC QD Week 48 analysis unblinding visit (i.e. after last subject has reached Week 48) CSS Phase III

Dolutegravir in first-line

Week 12 as an Early Predictor of Week 24 Outcomes in Trials of an Integrase Strand Transfer Inhibitor for HIV Martin, ICAAC 2015