Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection
Date
2022-01-01
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Abstract
[ABSTRACTS]. OBJECTIVE: To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs. DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2. DESIGN: Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks). METHODS: Participants with HIV-1 RNA ≤500 000 copies/ml and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC. RESULTS: At week 144, DTG + 3TC (N = 716) was noninferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA <50 copies/ml (Snapshot algorithm) in the pooled analysis (82% vs. 84%, respectively; adjusted treatment difference [95% confidence interval (CI)], -1.8% [-5.8, 2.1]), GEMINI-1 (-3.6% [-9.4, 2.1]), and GEMINI-2 (0.0% [-5.3, 5.3]). Twelve DTG + 3TC participants and nine DTG + TDF/FTC participants met protocol-defined confirmed virologic withdrawal (CVW) criteria; none developed treatment-emergent resistance. One DTG + 3TC participant who did not meet CVW criteria developed M184V at week 132 and R263R/K at week 144, conferring a 1.8-fold change in susceptibility to DTG; non-adherence to therapy was reported. Significantly fewer drug-related adverse events occurred with DTG + 3TC vs. DTG + TDF/FTC (20% vs. 27%; relative risk [95% CI], 0.76 [0.63-0.92]). Renal and bone biomarker changes favored DTG + 3TC. CONCLUSIONS: Three-year durable efficacy, long-term tolerability, and high barrier to resistance support first-line use of DTG + 3TC for HIV-1 treatment (see Supplemental Digital Content 1, http://links.lww.com/QAD/C297; video abstract).
Description
Fil: Cahn, Pedro. Fundación Huésped, Buenos Aires; Argentina
Fil: Sierra Madero, Juan. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; Mexico City, Mexico
Fil: Arribas, José R. Hospital Universitario La Paz; Madrid, Spain.
Fil: Antinori, Andrea. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani IRCCS; Rome, Italy
Fil: Ortiz, Roberto. Bliss Healthcare Services; Orlando, Florida, USA
Fil: Clarke, Amanda E. Royal Sussex County Hospital, and Brighton & Sussex Medical Schoo; Brighton, UK
Fil: Hung, Chien-Ching. National Taiwan University Hospital; Taipei, Taiwan
Fil: Rockstroh, Jürgen K. Department of Medicine, Universitätsklinikum Bonn; Bonn, Germany
Fil: Girard, Pierre-Marie. Hôpital Saint Antoine; Paris, France
Fil: Sievers, Jörg. ViiV Healthcar; Brentford, UK
Fil: Man, Choy Y. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Urbaityte, Rimgaile. GlaxoSmithKline; Stockley Park, UK
Fil: Brandon, Daisy J. GlaxoSmithKline; Stockley Park, UK
Fil: Underwood, Mark. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Pappa, Keith A. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Curtis, Lloyd. GlaxoSmithKline; Stockley Park, UK
Fil: Smith, Kimberly Y. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Gartland, Martin. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Aboud, Michael. ViiV Healthcare; Brentford, UK
Fil: van Wyk, Jean. ViiV Healthcare; Brentford, UK
Fil: Wynne, Brian. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Sierra Madero, Juan. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; Mexico City, Mexico
Fil: Arribas, José R. Hospital Universitario La Paz; Madrid, Spain.
Fil: Antinori, Andrea. Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani IRCCS; Rome, Italy
Fil: Ortiz, Roberto. Bliss Healthcare Services; Orlando, Florida, USA
Fil: Clarke, Amanda E. Royal Sussex County Hospital, and Brighton & Sussex Medical Schoo; Brighton, UK
Fil: Hung, Chien-Ching. National Taiwan University Hospital; Taipei, Taiwan
Fil: Rockstroh, Jürgen K. Department of Medicine, Universitätsklinikum Bonn; Bonn, Germany
Fil: Girard, Pierre-Marie. Hôpital Saint Antoine; Paris, France
Fil: Sievers, Jörg. ViiV Healthcar; Brentford, UK
Fil: Man, Choy Y. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Urbaityte, Rimgaile. GlaxoSmithKline; Stockley Park, UK
Fil: Brandon, Daisy J. GlaxoSmithKline; Stockley Park, UK
Fil: Underwood, Mark. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Pappa, Keith A. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Curtis, Lloyd. GlaxoSmithKline; Stockley Park, UK
Fil: Smith, Kimberly Y. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Gartland, Martin. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Fil: Aboud, Michael. ViiV Healthcare; Brentford, UK
Fil: van Wyk, Jean. ViiV Healthcare; Brentford, UK
Fil: Wynne, Brian. ViiV Healthcare, Research Triangle Park; North Carolina, USA
Keywords
Fármacos Anti-VIH, Síndrome de Inmunodeficiencia Adquirida