Strategic Simplification: The Efficacy and Safety of Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) plus Darunavir (DRV) in Treatment-Experienced HIV-1 Infected Adults (NCT01968551)

Background. Strategic simplification of an antiretroviral regimen with high pill burden and dosing frequency is a priority for treatment-experienced patients with multi-drug resistance. A single tablet with co-formulated E/C/F/TAF has demonstrated high efficacy and improved renal and bone safety compared with E/C/F/TDF in Phase 3 clinical trials. This study evaluated the efficacy and safety of switching to E/C/F/TAF +DRV in patients with ≥2-class resistance, including TDF resistance mutations (K65R, ≤3 TAMs). Methods. Virologically suppressed adults (N = 135) on a DRV-containing regimen for ≥4 months, with 2 prior failed regimens, and no history of Q151M, T69ins, or DRV RAMs, were randomized 2:1 to open-label E/C/F/TAF +DRV or to continue baseline regimen (BR). Week (W) 24 viral suppression (HIV-1 RNA <50 c/mL) by FDA snapshot analysis and safety data are reported. Results. Participants were older (median age 49), 25% female, 45% black, and 14% Hispanic. At entry, the median pills/regimen was 5, with 65% taking a twice-daily regimen, and a majority (58%) on a TDF-containing regimen. Viral suppression was maintained in 96.6% (86 of 89) in the E/C/F/TAF +DRV arm and 91.3% (42 of 46) in the BR arm (95% CI: −3.4%–17.4%). In the E/C/F/TAF +DRV arm, 2 patients had viremia at W24 but were suppressed at W36 and W48; 1 and 4 persons were missing data in the E/C/F/TAF +DRV and BR arms, respectively. There was no emergence of resistance. There were no differences in the median change in eGFR [2.5 in the E/C/F/TAF + DRV versus −0.1 mL/min in the BR arm (P = 0.62)] or urine protein/creatinine (Cr) ratio [−14% in the E/C/F/TAF +DRV arm versus −4% in BR arm (P = 0.21)]. Specific markers of proximal tubular proteinuria improved with E/C/F/TAF +DRV: median urine beta-2M/Cr decreased 35% (P < .001) and median urine RBP/Cr decreased 17% (P = .019), compared with increases of 11% and 13%, respectively, in the BR arm. There were no drug-related SAEs and no AEs leading to treatment discontinuation. Conclusion. Through W24, strategic simplification to E/C/F/TAF + DRV (2 pills once daily) maintained viral suppression, and the switch to TAF was associated with significant improvement in proximal tubular proteinuria. E/C/F/TAF +DRV may offer an attractive option for treatment-experienced patients on complex multi-tablet regimens. Disclosures. G. Huhn, Gilead: Consultant and Investigator, Consulting fee and Research support. Merck: Grant Investigator, Grant recipient. GSK/Viiv: Consultant and Investigator, Consulting fee and Research support. Janssen: Grant Investigator, Grant recipient; P. Tebas, Merck: Consultant, Consulting fee. Glaxo: Consultant, Consulting fee; J. Gallant, AbbVie: Investigator, Research support. Bristol-Myers Squibb: Investigator and Scientific Advisor, Consulting fee and Research support. Gilead Sciences: Investigator and Scientific Advisor, Consulting fee and Research support. Janssen Therapeutics: Investigator and Scientific Advisor, Consulting fee and Research support. Merck and Co.: Investigator and Scientific Advisor, Consulting fee and Research support. Sangamo BioSciences: Investigator, Research support. ViiV Healthcare: Investigator and Scientific Advisor, Consulting fee and Research support; T. Wilkin, GSK/Viiv: Consultant, Consulting fee. BMS: Investigator, Grant recipient. Gilead: Investigator, Grant recipient; A. Cheng, Gilead Sciences: Employee and Shareholder, Salary; M. Yan, Gilead Sciences, Inc: Employee and Shareholder, Salary; C. Callebaut, Gilead Sciences, Inc: Employee and Shareholder, Salary; M. Fordyce, Gilead Sciences, Inc: Employee and Shareholder, Salary; M. Das, Gilead Sciences, Inc: Employee and Shareholder, Salary; S. Mccallister, Gilead Sciences, Inc: Employee and Shareholder, Salary