Correlates of depressive symptoms in transgender women initiating HIV treatment in Argentina

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, https://links.lww.com/QAD/C297; video abstract).

Keywords

dolutegravir, integrase strand transfer inhibitor, nucleoside reverse transcriptase inhibitor, treatment-naive, two-drug regimen

Citation

Cahn, Pedroa; Sierra Madero, Juanb; Arribas, José R.c; Antinori, Andread; Ortiz, Robertoe; Clarke, Amanda E.f; Hung, Chien-Chingg; Rockstroh, Jürgen K.h; Girard, Pierre-Mariei; Sievers, Jörgj; Man, Choy Y.k; Urbaityte, Rimgailel; Brandon, Daisy J.l; Underwood, Markk; Pappa, Keith A.k; Curtis, Lloydl; Smith, Kimberly Y.k; Gartland, Martink; Aboud, Michaelj; van Wyk, Jeanj; Wynne, Briank. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy – naive adults with HIV-1 infection. AIDS 36(1):p 39-48, January 1, 2022. | DOI: 10.1097/QAD.0000000000003070