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ABSTRACT Background: Antiretroviral therapy use has led to a decline in HIV-related mortality yet disparities by gender and/or sexual orientation may exist. In this study, we estimated hazards of death in people living with HIV (PLWH) according to gender and sexual orientation. Methods: We included PLWH ≥ 18 years enrolled between 2000 and 2018 at INI/Fiocruz, Rio de Janeiro, Brazil. Participants were grouped as cisgender or transgender women, cisgender men who have sex with men (MSM) or men who have sex with women, or cisgender men with unknown sexual orientation. We assessed disparities in the hazard of death using Cox proportional hazards models. Results: Among 5,576 PLWH, median age at enrollment was 35 years, 39% were MSM, 28% cisgender women, 23% men who have sex with women, 5% transgender women, and 5% men with unknown sexual orientation. A total of 795 deaths occurred in 39,141 person-years of follow-up. Mortality rates per 1,000 person-years were: 82.4 for men with unknown sexual orientation, 24.5 for men who have sex with women, 18.3 for cisgender, 16.6 for transgender women, and 15.1 for MSM. Compared to MSM, men with unknown sexual orientation had the highest death hazard ratio (adjusted hazard ratio [aHR] 2.93, 95% confidence interval [CI] 2.35–3.81), followed by men who have sex with women (aHR 1.17, 95%CI 0.96, 1.43); death hazard ratios for cisgender and transgender women were not statistically different. Conclusion: We observed disparities in the hazard of death for men with unknown sexual orientation and men who have sex with women despite universal access to antiretroviral therapy in Brazil. Future work should characterize and assist men with unknown sexual orientation with tailored policies and interventions. Increased hazard of death was not observed for transgender women, which probably results from interventions implemented in our service to reach, engage, retain, and support this population. Background HIVrelated related andor exist study (PLWH Methods 1 200 201 INIFiocruz INI Fiocruz INI/Fiocruz Janeiro Brazil MSM (MSM models Results 5576 5 576 5,57 3 39 28 23 79 39141 141 39,14 personyears person followup. followup follow up. up follow-up 1000 000 1,00 824 82 4 82. 245 24 24. 183 18. 166 16 6 16. 151 15 15. adjusted aHR [aHR 293 2 93 2.93 95 CI [CI 2.35–3.81, 235381 2.35–3.81 , 81 2.35–3.81) 117 17 1.17 95CI 096 0 96 0.96 1.43 143 43 1.43) different Conclusion reach engage retain population 20 557 57 5,5 7 3914 14 39,1 100 00 1,0 8 29 9 2.9 23538 2.35–3.8 11 1.1 09 0.9 1.4 55 5, 391 39, 10 1, 2. 2353 2.35–3. 1. 0. 235 2.35–3 2.35– 2.35 2.3