Long-term durability of dolutegravir plus darunavir/cobicistat dual regimen in highly antiretroviral-experienced people with HIV (DoDaco study)

Background: A dolutegravir plus darunavir/cobicistat regimen has been used as a simplified option in heavily treatment-experienced people with HIV (PWH). We report on long-term results of this regimen as assessed by treatment discontinuation (TD) for any reason. Methods: This was a retrospective, observational, multicentre study. PWH started on dolutegravir plus darunavir/cobicistat from 1 December 2015 to 31 December 2022 were included. The primary endpoint was the rate of TD for any reason. Survival analysis with the Kaplan-Meier estimator was used to assess the probability of TD over time. Multiple Cox regression was used to estimate the probability of TD at 1 year following regimen initiation. Results: Three hundred and twenty-seven subjects were included. At baseline, 63.6% of individuals had HIV RNA of <50 copies/mL. Primary resistance-associated mutations for NRTIs, NNRTIs, PIs and integrase inhibitors were documented in 88.0%, 70.0%, 24.5% and 6.6%, respectively. Median follow-up was 4 years (IQR 3.3-6.9). Probability of TD was 8.3%, 13.0%, 18.0%, 22.0%, 25.0%, 30.0% and 35.0% after 1, 2, 3, 4, 5, 6 and 7 years of treatment, respectively. TD occurred in 83 subjects, largely due to death (n = 20), simplification (n = 13), toxicity (n = 11), intolerance (n = 9), drug interactions (n = 10) and virological failure (n = 7). At Cox regression analysis, factors associated with a higher probability of TD over time were baseline HIV RNA of >50 copies/mL (HR = 2.14, 95% CI 1.20-3.81; P = 0.01) and the presence of PI or integrase strand transfer inhibitor resistance mutations (HR = 5.48, 95% CI 2.42-12.4; P < 0.001). Conclusions: Dolutegravir plus darunavir/cobicistat is a durable combination in heavily treatment-experienced PWH. Those who were viraemic at the time of switch were more likely to discontinue, although most reasons for TD were other than virological failure.