Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57)
Por:
Podzamczer, D, Mican, R, Tiraboschi, J, Portilla, J, Domingo, P, Llibre, JM, Ribera, E, Vivancos, MJ, Morano, L, Masia, M, Gomez, C, Fanjul, F, Payeras, A, Inciarte, A, Estrada, V, Rivero, A, Castro, A, Bernal, E, Vinuesa, D, Knobel, H, Troya, J, Macias, J, Montero, M, Sanz, J, Navarro-Alcaraz, A, Caicedo, A, Fernandez, G, Martinez, E, Moreno, S
Publicada:
1 mar 2022
Ahead of Print:
1 feb 2022
Resumen:
D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated.
Background Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking. Methods Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B*5701 negative and hepatitis B virus negative), with viral load (VL) >= 500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL 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 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin). Results Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/mu L. Median weight was 73 kg and median body mass index was 24 kg/m(2). At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.
Filiaciones:
Podzamczer, D:
Hosp Univ Bellvitge, Barcelona, Spain
Mican, R:
Hosp La Paz, Madrid, Spain
Tiraboschi, J:
Hosp Univ Bellvitge, Barcelona, Spain
Portilla, J:
Hosp Gen Univ Alicante, Alicante, Spain
Domingo, P:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Llibre, JM:
Hosp Badalona Germans Trias & Pujol, Barcelona, Spain
Ribera, E:
Hosp Univ Vall dHebron, Barcelona, Spain
Vivancos, MJ:
Univ Alcala, Hosp Univ Ramon Y Cajal, IRYCIS, Madrid, Spain
Morano, L:
Hosp Univ Alvaro Cunqueiro, Vigo, Spain
Masia, M:
Hosp Gen Univ Elche, Elche, Spain
Gomez, C:
Hosp Univ Virgen de la Victoria IBIMA, Malaga, Spain
Fanjul, F:
Hosp Univ Son Espases, Palma De Mallorca, Spain
Payeras, A:
Hosp Univ Son Llatzer, Palma De Mallorca, Spain
Inciarte, A:
Hosp Clin Barcelona, Barcelona, Spain
Estrada, V:
Hosp Clin San Carlos IdiSSC, Madrid, Spain
Rivero, A:
Hosp Univ Reina Sofia, Cordoba, Spain
Castro, A:
Complejo Hosp Univ, La Coruna, Spain
Bernal, E:
Hosp Univ Reina Sofia, Murcia, Spain
Vinuesa, D:
Hosp Univ Clin San Cecilio, Granada, Spain
Knobel, H:
Hosp del Mar, Barcelona, Spain
Troya, J:
Hosp Univ Infanta Leonor, Madrid, Spain
Macias, J:
Hosp Univ Virgen Valme, Seville, Spain
Montero, M:
Hosp Univ & Politecn La Fe, Valencia, Spain
Sanz, J:
Hosp Univ Princesa, Madrid, Spain
Navarro-Alcaraz, A:
Hosp Univ Bellvitge, Barcelona, Spain
Caicedo, A:
RIS Red Invest SIDA, Madrid, Spain
Fernandez, G:
Hosp Univ Bellvitge, Barcelona, Spain
Martinez, E:
Hosp Clin Barcelona, Barcelona, Spain
Moreno, S:
Univ Alcala, Hosp Univ Ramon Y Cajal, IRYCIS, Madrid, Spain
Green Published, gold
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