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Evolution of Causes of Death in People With HIV Between 2000 and 2023: A Single-Center Retrospective Study in Milan, Italy
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JAIDS Jan 1 2026
To the Editors:
The introduction of antiretroviral therapy (ART) revolutionized the prognosis of people living with HIV (PWH), significantly reducing mortality and transforming HIV infection to a manageable chronic disease.1 In the 1980s and 1990s, when effective treatments were unavailable, mortality was mainly because of complications from opportunistic infections and HIV-associated cancers.2 With the advent of ART in the mid-1990s, AIDS-related mortality drastically declined and the prevalence of non-AIDS-related cancers has increased.3,4 In addition, PWH are at significantly increased cardiovascular risk compared with the general population5 and they also have a greater prevalence of chronic liver diseases, because of coinfections with hepatotropic viruses, potential hepatotoxic effects of ART, and higher prevalence of nonalcoholic fatty liver disease.6
Understanding the causes of death is pivotal in PWH to tailor preventive interventions. Thus, the authors analyzed the evolution of causes of death in a large cohort of PWH.
In conclusion, this study highlights a significant shift in the cause of death of PWH, characterized by a decrease in the proportion of AIDS-related deaths and an increase in deaths related to age-associated comorbidities. The authors’ findings support the need for targeted preventive and therapeutic strategies that address the new challenges associated with the aging HIV population. Optimizing comorbidity management, integrating prevention and treatment services, and continuously improving ART therapies are essential steps to further enhance the quality of life and survival of people living with HIV.
Overall, the most frequent cause of death was AIDS related (135 deaths, 20.2%), primarily because of AIDS-related infections (62, 9.3%) and AIDS-related cancers (54, 8.1%). Over time, there was a significant decrease in the proportion of AIDS-related deaths (from 33.4% in 2000–2010 to 7.9% post-2016, P < 0.001) and liver disease-related deaths (from 18.1% in 2011–2015 to 10.9% post-2016, P = 0.02). In contrast, the proportion of deaths due to non-AIDS-related cancers significantly increased from 13.8% to 24.9% (P = 0.01), as did those caused by cardiovascular events, rising from 5.9% to 11.4% (P = 0.04).
Across all 3 periods, non-Hodgkin lymphomas were the most frequently reported AIDS-related cause of death, accounting for 29.9%, 30.0%, and 38.9%, respectively (Supplemental Digital Content, Figure, https://links.lww.com/QAI/C570).
An analysis of causes of death between 2016 and 2023, stratified by sex at birth and age at death (≤44 years, 45–64 years, ≥65 years), revealed that non-AIDS-related cancers remained the most frequent cause of death in both men and women. Cancer is the leading cause of death among individuals younger than 65 years (accounting for 27.3% of deaths in those younger than 45 years and 25.8% in the 45–64 age group), while in those older than 65 years, cancer and cardiovascular diseases are equally common causes of death, each representing 21.8%.
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