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Lancet. 2019 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9.

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.

Collaborators (189)

Cassetti L, David D, Figueras L, Losso M, Lopardo G, Lupo S, Porteiro N, Sánchez 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 JC, Demeester R, Lacor P, Vandercam B, Vandekerckhove L, Angel J, Baril JG, Conway B, De Pokomandy A, Szabo J, Walmsley S, Bouchaud O, Chidiac C, Delobel P, Goujard C, Katlama C, Molina JM, Pialoux G, Philibert P, Bogner J, Esser S, Krznaric I, Lehmann C, Spinner C, Stellbrink HJ, Stephan C, Stoehr A, Barchi E, Caramello P, Castelli F, Cattelan AM, 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 ER, Perez Rios A, Santoscoy Gomez M, Den Hollander J, Rijnders B, Hidalgo JA, Hercilla Vasquez L, Illescas L, Olczak A, Mansinho K, Correia Pacheco PP, Teófilo E, Saraiva da Cunha J, Sarmento E Castro R, Serrão R, Arbune M, Jianu C, Oprea A, Preotescu L, Prisacariu LJ, 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 SH, Kim SW, Kim SI, Kim WJ, Antela Lopez A, Casado Osorio JL, Castaño Carracedo MA, De Los Santos Gil I, Estrada Perez V, Falco Ferrer V, Force L, Galinda Puerto MJ, Garcia Deltoro M, Gatell JM, Goenaga Sanchez MA, González Cordón A, Knobel H, Lopez Bernaldo de Quiros JC, Losa Garcia JE, Masia M, Montero-Alsonso M, Ocampo Hermida A, Pasquau Liaño J, Portilla Sogorb J, Pulido Ortega F, Rivera Roman A, Santos Fernandez JR, Torres Perea R, Troya Garcia J, Viciana Fernandez P, Calmy A, Hauser C, Fehr J, Cheng SH, Ko WC, Lin HH, Lu PL, Tseng YT, Wang NC, Wong WW, Yang CJ, 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.

Author information

1
Department of Infectious Diseases, Buenos Aires University, Buenos Aires, Argentina; Fundación Huésped, Buenos Aires, Argentina.
2
Infectious Diseases, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.
3
Hospital Universitario La Paz, Instituto de Investigación Hospital La Paz, Madrid, Spain.
4
UOC Immunodeficienze virali, Instituto Nazionale per le Malattie Infettive Lazzaro Spallanzani-IRCCS, Rome, Italy.
5
Bliss Healthcare Services, Orlando, FL, USA.
6
Sexual Health and Clinical Trials, Royal Sussex County Hospital, Brighton, UK.
7
Division of Infectious Diseases, National Taiwan University Hospital, Taipei, Taiwan.
8
Department of Medicine, University Hospital Bonn, Bonn, Germany.
9
Service des Maladies Infectieuses et Tropicales, Hôpital Saint Antoine, Paris, France.
10
Clinical Development, ViiV Healthcare, Brentford, UK. Electronic address: jorg.x.sievers@viivhealthcare.com.
11
Clinical Development, ViiV Healthcare, Research Triangle Park, NC, USA.
12
Statistics, GlaxoSmithKline, Stockley Park, UK.
13
Clinical Virology, ViiV Healthcare, Research Triangle Park, NC, USA.
14
Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Stockley Park, UK.
15
Medicine Development, ViiV Healthcare, Research Triangle Park, NC, USA.
16
Global Medical Affairs, ViiV Healthcare, Brentford, UK.
17
Global Research and Medical Strategy, ViiV Healthcare, Research Triangle Park, NC, USA.

Erratum in

Abstract

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.

PMID:
30420123
DOI:
10.1016/S0140-6736(18)32462-0
[Indexed for MEDLINE]

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