119 The Anti-HIV Drug Pipeline

New Drugs by Class NRTI: Tenofovir alafenamide fumarate (TAF) is the pro-drug of tenofovir with advantages of slight increase activity and reduced renal/bone toxicity. The phase 2 trial (Zolopa A. 2012 CROI, Abstr 99LB) compared TAF vs. another TDF prodrug (TFV, each with EFV, COBI/FTC in 170 treatment naïve patients. At 24 weeks both groups achieved VL <50 c/mL; TAF showed better renal and bone safety. INSTI: Dolutgravir (DTG)—New once daily DTG/2NRTIs that shows potency with good activity vs. RAL-resistant strains. • S/GSK 1265-744 (˙744”): This is a next generation InSTI with a T1/2 of 21-50d! NNRTI: MK1439—This new potent NNRTI showed exceptional potency with 25 mg monotherapy once daily (Anderson M, 2013 CROI; Abstr. 100). • RPV-LA: A novel nanosuspension of RPV with steady state release after 600 mg given SC or IM every 3 months. ENTRY INHIBITORS: Cenicriviroc (CVC) antagonizes CCR5 receptor, but also CCR-2 receptors to possibly reduce immune activation. ART activity is comparable to EFV. • BMS 663068 (or BMS 068): This is a prodrug of BMS-529 that binds gp125 to prevent HIV binding to CD4 cells. A small trial showed 42 of 48 treatment-naïve patients responded; the 6 exceptions had a genetic factor that accounted for nonresponse. PHARMACOENHANCER: Cobicistat (COBI) is a potential substitute for RTV to boost ARVs and is already FDA-approved in combination as EVG/COBI/TDF/FTC.