Clarifying INSTINCT: Switching From DTG/3TC to BIC/FTC/TAF Shows Comparable Inflammatory and Weight Outcomes

We thank Dr. Martnez for engaging with our work.We were surprised to see the biological rationale questioned based on two citations presenting only observational data which cannot establish causality.This is precisely why randomized trials like INSTINCT were necessary.This critique is particularly unexpected given the correspondent's own research: The correspondent led the DOLAM metabolomic substudy, which found that switching from triple therapy to dolutegravir/lamivudine produced some circulating metabolomic perturbations [1].This exemplifies the scientific inquiry INSTINCT pursued -testing whether reintroducing a third agent alters inflammation and metabolism, grounded in plausible mechanisms including tissue penetration and NRTI effects, a question addressed by multiple contemporaneous trials [2][3][4][5][6].Regarding generalizability: Unlike recent trials in this field such as PASO-DOBLE, which enrolled patients on optimizable multi-tablet regimens [7], INSTINCT randomized individuals already established on DTG+3TC-a population with baseline characteristics representative of current DTG/3TC users at least in Western countries (Table 1) [8].This design directly tests