Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naïve Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57)

Abstract

Background: We performed the first head-to-head randomized comparison between D/C/F/TAF and DTG/ABC/3TC in antiretroviral-naive patients. Both treatments were administered as single-tablet regimens. Methods: Adult (>18 y) HIV-infected antiretroviral-naive patients (HLA B5701– and HBV-negative), with VL ≥500 c/mL, were centrally randomized after stratifying by viral load and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 (ITT exposed [ITTe], snapshot analysis), with a non-inferiority margin of 10%. Results: Of 316 subjects randomly assigned to treatment, 306 patients were included in the ITTe analysis (151 and 155) Of these, 94% were male, median age was 35 years, and 79% were men who have sex with men, viral load was 64,848 c/mL, CD4 408/µL, , weight 73 kg, and BMI 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) vs 82% (DTG/3TC/ABC) had VL <50 c/mL (difference –2.4%, 95%CI –11.3 to 6.6). Virologic failure rates were 8% vs 4%, drugs were discontinued due to adverse events in 4% vs 6%, and 8% were lost to follow-up in each arm. In the per protocol analysis, 94% vs 96% patients had VL <50 c/mL (difference –2%, 95%CI –8.1 to 3.5). Three sensitivity ITT analyses were concordant with the primary endpoint. No differences were found in CD4 count increase (+226 vs +260/µL, p=0.1), weight increase (3.0 vs 2.9 kg, p=0.8), or BMI (1.0 vs 0.96 kg/m2, p=0.8) at week 48. The dolutegravir regimen had a more favourable lipid profile and darunavir was associated with lower creatinine (p=0.004) and glucose (p=0.021) increases. No RAMs emerged in any study participant. Conclusions: D/C/F/TAF administered as a single-tablet regimen did not prove to be non-inferior to DTG/ABC/3TC in the ITTe or in the ITT sensitivity analyses. Both regimens were well tolerated, with a similar increase in CD4 counts, weight, and BMI. D/C/F/TAF is an efficacious and well-tolerated alternative to INSTI regimens in antiretroviral-naive patients. Clinical Trial Registration Details: EudraCT Number: 2018-001645-14. Funding Information: Spanish AIDS Research (RIS). Declaration of Interests: DP has received research grants from Gilead, MSD, and ViiV and honoraria for advisory boards and/or conferences from Gilead, MSD, ViiV, and Janssen. SM taken part in speaking activities and has received grants for research from Gilead, Janssen Cilag, Merck Sharp&Dohme, and ViiV Healthcare. JT has received financial compensation for lectures, consultancies, and educational activities, as well as research funding for from Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare. JP has received honoraria for advisories and/or conferences from Gilead, MSD, ViiV and Janssen. JML has received honoraria for advisories and/or conferences from Gilead, ViiV, Theratechnologies and Janssen. ER reports personal fees from MSD, personal fees from Gilead, personal fees from Janssen, personal fees from ViiV Healthcare, outside the submitted work. LM reports having received consulting fees from, Abbvie and Janssen Cilag and has received lecture fees from Abbvie, Janssen Cilag, ViiV and Gilead. MM has received honoraria for advisories and/or conferences from ViiV, Janssen and MSD. AR has received grants for research, educational and advisory activities, from Gilead Sciences, ViiV Healthcare, Janssen Cilag, Abbvie and Merck Sharp&Dohm. FF has received research grants from Gilead and honoraria for advisories and/or conferences from Gilead, MSD, Viiv and Jansen. AP has received honoraria for advisories and/or conferences from Gilead, ViiV and Janssen Cilag. VE has received honoraria for advisory boards and/or conferences from ViiV Healthcare, Janssen, Gilead, MSD Y Thera tech. HK has received financial compensation for consulting work and conferences from Gilead Sciences, Janssen, Merck Sharp Dome and ViiV Healthcare. JTG has been involved in speaking activities from Gilead, Janssen Cilag, and Merck Sharp&Dohme. JM has received honoraria for advisory boards and/or conferences from Gilead, Bristol-Myers Squibb Merck Sharp&Dohme. JS has received financial compensation for consulting work and conferences from Gilead Sciences, Janssen, Merck Sharp Dome and ViiV Healthcare. EM reports grants and personal fees from MSD, grants and personal fees from ViiV Healthcare, personal fees from Gilead, and personal fees from Janssen, outside the submitted work. SM has been involved in speaking activities and has received grants for research from Gilead, Janssen Cilag, Merck Sharp&Dohme, and ViiV Healthcare. RM, PD, CG, AI, AC, DV, MM, AN-A, AC, GF. EB and MPE have no conflict of interests to declare. Ethics Approval Statement: This trial was performed in accordance with the Declaration of Helsinki and approved by the local ethics committees and the Spanish Agency for Medicines and Medical Devices. All participants gave their written informed consent.