Background: Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods: We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings: Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation: The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding: ViiV Healthcare.
Cahn, P., Madero, J., Arribas, J., Antinori, A., Ortiz, R., Clarke, A., et al. (2019). Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. THE LANCET, 393(10167), 143-155 [10.1016/S0140-6736(18)32462-0].
|Citazione:||Cahn, P., Madero, J., Arribas, J., Antinori, A., Ortiz, R., Clarke, A., et al. (2019). Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. THE LANCET, 393(10167), 143-155 [10.1016/S0140-6736(18)32462-0].|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials|
|Autori:||Cahn, P; Madero, J; Arribas, J; Antinori, A; Ortiz, R; Clarke, A; Hung, C; Rockstroh, J; Girard, P; Sievers, J; Man, C; Currie, A; Underwood, M; Tenorio, A; Pappa, K; Wynne, B; Fettiplace, A; Gartland, M; Aboud, M; Smith, K; Cassetti, L; David, D; Figueras, L; Losso, M; Lopardo, G; Lupo, S; Porteiro, N; Sanchez, M; Bloch, M; Cooper, D; Finlayson, R; Kelleher, A; Koh, K; Lewis, D; McMahon, J; Moore, R; Roth, N; Shields, M; De Wit, S; Florence, E; Goffard, J; Demeester, R; Lacor, P; Vandercam, B; Vandekerckhove, L; Angel, J; Baril, J; Conway, B; De Pokomandy, A; Szabo, J; Walmsley, S; Bouchaud, O; Chidiac, C; Delobel, P; Goujard, C; Katlama, C; Molina, J; Pialoux, G; Philibert, P; Bogner, J; Esser, S; Krznaric, I; Lehmann, C; Spinner, C; Stellbrink, H; Stephan, C; Stoehr, A; Barchi, E; Caramello, P; Castelli, F; Cattelan, A; D'Arminio Monforte, A; Di Biagio, A; Di Perri, G; Gori, A; Maggiolo, F; Menzaghi, B; Migliorino, G; Mussini, C; Penco, G; Puoti, M; Rizzardini, G; Gulminetti, R; Lazzarin, A; Quirino, T; Sighinolfi, L; Viale, P; Amaya Tapia, G; Andrade Villanueva, J; Granados Reyes, E; Perez Rios, A; Santoscoy Gomez, M; Den Hollander, J; Rijnders, B; Hidalgo, J; Hercilla Vasquez, L; Illescas, L; Olczak, A; Mansinho, K; Correia Pacheco, P; Teofilo, E; Saraiva da Cunha, J; Sarmento e Castro, R; Serrao, R; Arbune, M; Jianu, C; Oprea, A; Preotescu, L; Prisacariu, L; Belonosova, E; Borodkina, O; Chernova, O; Gankina, N; Kizhlo, S; Kulagin, V; Kurina, N; Nagimova, F; Pokrovsky, V; Ryamova, E; Voronin, E; Yakovlev, A; Kaplan, R; Lee, S; Kim, S; Kim, S; Kim, W; Antela Lopez, A; Casado Osorio, J; Castano Carracedo, M; De Los Santos Gil, I; Estrada Perez, V; Falco Ferrer, V; Force, L; Galinda Puerto, M; Garcia Deltoro, M; Gatell, J; Goenaga Sanchez, M; Gonzalez Cordon, A; Knobel, H; Lopez Bernaldo de Quiros, J; Losa Garcia, J; Masia, M; Montero-Alsonso, M; Ocampo Hermida, A; Pasquau Liano, J; Portilla Sogorb, J; Pulido Ortega, F; Rivera Roman, A; Santos Fernandez, J; Torres Perea, R; Troya Garcia, J; Viciana Fernandez, P; Calmy, A; Hauser, C; Fehr, J; Cheng, S; Ko, W; Lin, H; Lu, P; Tseng, Y; Wang, N; Wong, W; Yang, C; Arduino, R; Benson, P; Berhe, M; Bredeek, F; Brinson, C; Campbell, T; Crofoot, G; Cunningham, D; DeJesus, E; Dretler, R; Eron, J; Fife, K; Fichtenbaum, C; Flamm, J; Goldstein, D; Gupta, S; Hagins, D; Hoffman-Terry, M; Jayaweera, D; Kinder, C; Klein, D; McDonald, C; Mills, A; Nahass, R; Osiyemi, O; Overton, E; Parks, D; Prelutsky, D; Ramgopal, M; Schrader, S; Sha, B; Simon, G; Sims, J; Skiest, D; Slim, J; Tashima, K; Thedinger, B; Gazzard, B; Fox, J; Johnson, M; Kegg, S; Khoo, S; Mazhude, C; Orkin, C; Schembri, G; Ustianowski, A|
|Data di pubblicazione:||2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0140-6736(18)32462-0|
|Appare nelle tipologie:||01 - Articolo su rivista|