Background. Understanding the evolution and dynamics of deaths in people with HIV (PWH) is crucial to tailor interventions aiming at improving PWH long-term well-being. We aimed to assess all-cause and cause-specific mortality in PWH in Italy. Methods. PWH enrolled before antiretroviral start from Icona cohort (78 Italian HIV clinics) between 1997 and 2021 (last observation December 2022) were included. Mortality was reported as incidence rate per 100 person-years of follow-up (PYFU). The mortality incidence rate according to calendar period was estimated by Poisson regression model. Results. Overall, 17,006 PWH were included of whom 1584 (9.31%) died. The highest mortality rates were observed during the earliest calendar periods, with 2.67 (95% CI: 2.19–3.25) and 1.93 (95% CI: 1.67–2.22) deaths per 100 PYFU in 1997–1998 and 1999–2001, respectively. After 2010, mortality rates fell below 1 per 100 PYFU, reaching 0.74 (95% CI: 0.65–0.84) and 0.71 (95% CI: 0.63–0.80) in 2017–2019 and 2020–2022, respectively. A significant drop was observed for AIDS-related mortality in the first two periods from 1.45 (95% CI: 1.11–1.90) in 1997–1998 to 0.78 (95% CI: 0.62–0.97) deaths per 100 PYFU in 1999–2001. AIDS-related mortality continued to decrease in the subsequent years, with the lowest rate observed in the last two calendar periods: 0.10 (95% CI: 0.07–0.14) deaths per 100 person-years in 2017–2019 and 0.10 (95% CI: 0.08–0.15) deaths per 100 person-years in 2020–2022. Conclusions. All-cause mortality in PWH in Italy significantly decreased over time, mainly for a reduction in AIDS-related mortality.
