Real world efficacy of dolutegravir plus lamivudine in PLWH with undetectable viral load after previous failures

Background: Dolutegravir (DTG) +lamivudine (3TC) combination has shown to be as effective as triple therapy as maintenance therapy and has been extensively prescribed in clinical practice. We aimed to investigate the impact of previous virological failures (VF) on virological efficacy. Methods: The analysis included data of PLWH with HIV-RNA≤50 copies/mL enrolled in an Italian retrospective multi-cohort study, switching to DTG+3TC. Primary endpoint was viral rebound (VR, confirmed HIV-RNA ≥ 50 copies/mL or a single HIV-RNA ≥ 50 copies/mL followed by change of ART). Kaplan-Meier curves were used to estimate probabilities of VR according to history of previous VF (single HIV-RNA >=1000 or confirmed HIV-RNA >=50 copies/mL). A weighted Cox regression model was fitted to estimate the causal hazard ratio (HR) of history of failure on the risk of VR. Results: A total of 966 PLWH were included, 20.1% of them with history of previous VF. VR was detected in 23 PLWH. The 1-year probability was 1.2% (95% CI 0.2%-2.2%) in PLWH without previous VF and 3.3% (95% CI 0.4%-6.2%) in those with >= 1 VF (log-rank p=0.042). By multivariate analysis adjusted for CD4+ cells count at nadir, duration of virological suppression and mode of HIV transmission, PLWH with >= 1 previous VF had a higher risk of virological rebound than those without previous VF (adjusted HR 3.06 [95% CI 1.00-9.44], p=0.051). Conclusions: Despite the low absolute 1 year risk in both groups, real-world data confirmed that PLWH with a previous failure have an increased risk of viral rebound.