Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy - naive adults with HIV-1 infection

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 I IIV-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; nonadherence 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 DIG + 3TC for HIV-1 treatment Copyright (C) 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Automated summary

The study assessed the efficacy and safety of dolutegravir lamivudine compared to dolutegravir with tenofovir disoproxil fumarate/emtricitabine in treatment-naive adults with HIV-1. The results showed that dolutegravir lamivudine was noninferior to dolutegravir with tenofovir disoproxil fumarate/emtricitabine in terms of virologic response. The dolutegravir lamivudine group had a lower rate of adverse events and less impact on renal and bone biomarkers. These findings support the use of dolutegravir lamivudine as a first-line treatment for HIV-1.