AIDS | 2021
Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naive adults with HIV-1 infection.
Abstract
OBJECTIVE\nTo 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.\n\n\nDESIGN\nIdentical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96\u200aweeks).\n\n\nMETHODS\nParticipants with HIV-1 RNA ≤500,000\u200acopies/mL and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.\n\n\nRESULTS\nAt Week 144, DTG + 3TC (N\u200a=\u200a716) was non-inferior to DTG + TDF/FTC (N\u200a=\u200a717) in proportion of participants achieving HIV-1 RNA <50\u200acopies/mL (Snapshot algorithm) in the pooled analysis (82% vs 84%, respectively; adjusted treatment difference [95% 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 9 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 M184\u200aV 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.\n\n\nCONCLUSIONS\nThree-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, video abstract, http://links.lww.com/QAD/C297).