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SIGNIFICANT EFFICACY & LONG-TERM SAFETY DIFFERENCE WITH TAF-BASED STR IN NAÏVE ADULTS
Jose R. Arribas1, Melanie Thompson2, Paul E. Sax3, Bernhard Haas4, Cheryl McDonald5, David Wohl6, Edwin DeJesus7, Amanda Clarke8, Moupali Das9, Scott McCallister9
1Hosp Univ La Paz, Madrid, Spain,2AIDS Rsr Consortium of Atlanta, Atlanta, GA, USA,3Brigham and Women's Hosp, Boston, MA, USA,4Hosp Graz West, Graz, Austria,5Tarrant County Infectious Disease Associates, Fort Worth, TX, USA,6Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA,7Orlando Immunol Cntr, Orlando, FL, USA,8Brighton & Sussex Univ Hosps NHS Trust, Brighton, UK,9Gilead Scis, Inc, Foster City, CA, USA
Two randomized, controlled, double-blinded multinational Phase 3 trials compared tenofovir alafenamide (TAF) vs tenofovir disoproxil fumarate (TDF), each in single-tablet regimens coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At Week (W) 48, E/C/F/TAF was statistically noninferior to E/C/F/TDF for the proportion of subjects with HIV-1 RNA <50 copies(c)/mL and had significant improvements in renal and bone safety endpoints. We now describe follow up of blinded data through W144, including longer-term safety data and prespecified <20 c/mL secondary endpoint.
ARV naïve participants randomized 1:1 to receive E/C/F/TAF (TAF) or E/C/F/TDF (TDF). W144 viral suppression (HIV-1 RNA <50 and <20 c/mL) by FDA snapshot analysis, predefined bone and renal safety, and tolerability endpoints are reported.
1,733 HIV-infected adults were randomized and treated: 15% women, 43% non-white, 23% viral load >100,000 c/mL. Median baseline characteristics: age 34 yrs, CD4 count 405 cells/µL, and VL 4.58 log10 c/mL. At W144, TAF met prespecified criteria for both noninferiority and superiority to TDF by FDA snapshot algorithm (HIV-1 RNA <50 and <20 c/mL) (Table 1). Mean % decrease in BMD was significantly less in the TAF group for both lumbar spine and total hip (Table 1). As shown in Table 1, multiple measures of renal safety were significantly better for participants randomized to TAF. There were no cases of renal tubulopathy in the TAF arm vs 2 on TDF. No participants on TAF had renal-related discontinuations vs 12 on TDF (p<0.001). Participants on TAF had greater increases in TC, LDL, and HDL (Table 1), with no difference in the rate of initiation of lipid-modifying agents (TAF: 5.5% vs TDF: 5.8%).
Through W144, participants on E/C/F/TAF had a significantly higher rate of virologic suppression (<50 c/mL) than those on E/C/F/TDF, driven by fewer participants on E/C/F/TAF with no W144 data. Participants on E/C/F/TAF also had a significantly higher rate of virologic suppression (<20 c/mL), driven by fewer participants on E/C/F/TAF with viral load ≥20 c/mL. E/C/F/TAF continued to have a statistically superior bone and renal safety profile compared to E/C/F/TDF, demonstrating significant safety advantages over E/C/F/TDF through 3 years of treatment. Individuals on TAF had greater plasma lipid changes, but proportions starting lipid-lowering therapy were comparable.