Low proportion of individuals develop Metabolic Syndrome (MetS) or hepatic fibrosis after switch to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in virologically suppressed patients: a post-hoc metabolic analysis

BACKGROUND: Greater weight gain has been observed following initiation of integrase inhibitor (INI)-based regimens compared to non-nucleoside reverse transcriptase inhibitor- or boosted protease inhibitor (bPI)-based regimens and after switching from tenofovir disoproxil fumarate (TDF) to TAF, particularly with an INI. Little is known about the implications of weight gain on metabolic parameters and advanced hepatic fibrosis in people with HIV-1. Among EMERALD patients who switched from bPI+F/TDF to D/C/F/TAF at baseline, median weight change was +1.3kg at Wk48. This post-hoc analysis evaluated the proportion of EMERALD patients with baseline and developing MetS and advanced hepatic fibrosis.
METHODS: The phase 3 EMERALD study (ClinicalTrials.gov:NCT02269917) randomized (2:1) virologically suppressed adults receiving bPI+F/TDF to switch to once-daily D/C/F/TAF 800/150/200/10mg or continue their current regimen. This post-hoc analysis evaluated proportion of patients who met criteria for MetS (per International Diabetes Federation definition) and advanced hepatic fibrosis (according to nonalcoholic fatty liver disease [NAFLD] fibrosis score) at Wk48 in each treatment arm.
RESULTS: At baseline, 108/760 (14.2%) and 35/377 (9.3%) patients receiving D/C/F/TAF and control regimen, respectively, had MetS. At Wk48, 108/725 (14.9%) and 49/356 (13.8%) patients receiving D/C/F/TAF and control regimen had MetS, representing changes from baseline of +0.8% and +4.2%, respectively. Among these patients, the most frequently observed MetS components at baseline were hypertension and hypertriglyceridemia; findings were similar at Wk48 (Figure). According to NAFLD score, the proportion of patients with advanced hepatic fibrosis at baseline was low (D/C/F/TAF, 17/739 [2.3%]; control, 4/362 [1.1%]) and remained low at Wk48 (D/C/F/TAF, 20/691 [2.9%]; control, 5/343 [1.5%]).
CONCLUSIONS: At Wk48, switching to D/C/F/TAF did not appear to be associated with increased prevalence of MetS or hepatic fibrosis compared to continuing bPI+F/TDF. The minimal change in weight observed for these patients in EMERALD did not appear to impact the metabolic parameters described here, even when switching from TDF to TAF.