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Objective: To evaluate immunogenicity and reactogenicity of yellow fever (YF) vaccine in people with HIV (PWH) compared to HIV-uninfected controls., Design: In this longitudinal interventional trial (NCT03132311), PWH with CD4 + cell count ≥200 cells/μl and controls, aged 18-59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1., Methods: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers., Results: Two hundred and eighteen PWH and 82 controls were included. At baseline, all PWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 + cell count was 630 cells/μl [interquartile range (IQR) 463-888]. YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PWH [95% confidence interval (CI): 95.6-99.6] and in 100% of controls (95% CI: 93.9-100); at Year 1, 94.0% of PWH (95% CI: 89.6-96.7) and 98.4% of controls (95% CI 90.3-99.9) were seropositive. PWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1000 copies/ml, low CD4 + cell count and low CD4 + /CD8 + ratio were associated with lower YF-neutralization titers., Conclusions: YF vaccine is safe in PWH with CD4 + cell count ≥200 cells/μl. YF vaccine immunogenicity is impaired in PWH, particularly among those with high VL, low CD4 + cell count and low CD4 + /CD8 + ratio at vaccination and YF-neutralization titers decays over time., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)