Long‑Term Effectiveness and Safety of Doravirine‑Based Antiretroviral Regimens in Virologically Suppressed People with HIV: The French Dat'AIDS Cohort.

INTRODUCTION: Doravirine (DOR)-based regimens are recommended as alternative options for virologically suppressed people with HIV (VS-PWH). However, data supporting their long-term use in real-world settings are scarce. This large study described the long-term effectiveness and safety of DOR-based regimens following treatment switch in routine clinical practice. METHODS: Retrospective cohort study using data from Dat'AIDS, a French standardized database that collects real-world medical data from PWH across France. All treatment-experienced adults with confirmed plasma HIV-1 RNA < 50 copies/ml who initiated a DOR-based regimen for the first time between April 2019 and June 2024 were included. Baseline demographic and clinical characteristics, proportions of PWH receiving a DOR-based regimen and maintaining virologic suppression, and reasons for treatment discontinuation were collected. PWH were censored at the time of discontinuing DOR, death, or end of study (December 2024). RESULTS: Data from 1666 VS-PWH (median age 56 years, interquartile range: 47-63; 65% male; 31% with obesity) were analyzed. Just before switching, 49% and 38% were receiving an integrase strand transfer inhibitor (INSTI) or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen combined with at least one nucleo(t)side reverse transcriptase inhibitor (NRTI). Most (80%) switched to a triple therapy, mainly DOR/3TC/TDF (74%). Virologic suppression was maintained in 97% of PWH at 12 months (96% at 48 months). Only small changes in body weight, lipid parameters, and renal or hepatic function were observed during follow-up. Among the 45 discontinuations of DOR-based regimens, 11 were due to adverse events and two due to protocol-defined virologic failure, with no observed resistance to antiretroviral treatments. CONCLUSIONS: In this study, reporting the largest cohort of people receiving DOR-based regimens to date, DOR-based regimens demonstrated durable virologic effectiveness and a very favorable safety profile in treatment-experienced people with HIV and multiple comorbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT02898987.