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

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. 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). 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. 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. ClinicalTrials.gov NCT02898987. Doravirine may be used in individuals with HIV who have achieved virologic suppression. However, data on the long-term outcomes of doravirine-based treatments in real-world settings are limited. This large national observational study assessed the long-term effectiveness and safety of doravirine-based treatments in routine clinical practice using the French Dat’AIDS database. The study included all adults with HIV and confirmed HIV-1 RNA levels below 50 copies/ml who initiated their first doravirine-based treatment between April 2019 and June 2024. Included individuals were monitored until treatment switch to a doravirine-free regimen, death, or end of follow-up (December 2024). We assessed demographic and clinical characteristics, reasons for discontinuation of doravirine-based treatments, and virological suppression among 1666 middle-aged individuals living with HIV (65% male; 31% with obesity). Prior to initiating doravirine-based treatment, 49% and 38% were on treatments containing integrase strand transfer inhibitors (INSTIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) with at least one nucleoside reverse transcriptase inhibitor (NRTI). The majority (80%) switched to a triple therapy regimen, primarily doravirine/lamivudine/tenofovir disoproxil fumarate (73.6%). Viral suppression was sustained in 97% of people with HIV at 12 months and 96% at 48 months. Among the 45 individuals who discontinued doravirine-based treatment, 11 reported adverse events, and two experienced viral rebound without developing drug resistance. The effectiveness of doravirine-based treatments observed in this large observational study, along with its favorable clinical, metabolic, and biological safety profile, supports their use in virologically suppressed people with HIV with prior treatment experience who require or desire a treatment change.