Trends in AIDS-defining illnesses among people living with HIV in clinical care in Europe: results from the EuroSIDA multicentre cohort study (2003-24)

Background Despite substantial declines in AIDS-defining illnesses following implementation of treat-all policies across Europe, these conditions remain a substantial cause of morbidity and mortality among people with HIV. This study aimed to describe temporal trends in AIDS-defining illnesses across Europe, including trends in the incidences of specific illnesses, and to investigate associated risk factors. Methods Adults with HIV in clinical care were enrolled consecutively at 113 collaborating clinics in EuroSIDA, a prospective longitudinal cohort study, with data collected annually from routine clinical visits. Participants under follow-up in the WHO European region during 2003-24 were included in analyses. AIDS-defining illnesses were defined using the clinical conditions from the US Centers for Disease Control 1993 AIDS case definition. AIDS-related deaths were identified using the Coding Causes of Death in HIV methodology. In the primary analysis, we included all initial AIDS-defining illnesses that occurred during prospective follow-up, with follow-up censored after diagnosis of an AIDS-defining illness. Incidence rates of AIDS-defining illnesses and AIDS-related deaths were calculated as number of events per 1000 person-years of follow-up. Multivariable Poisson regression was used to compare incidence of AIDS-defining illnesses across regions, calendar time periods, and clinical and demographic factors. Findings 22 119 adults with HIV who contributed follow-up between Jan 1, 2003, and Dec 31, 2024 (16 086 [72·7%] male and 6017 [27·2%] female participants, median age 41 years [IQR 34-49]) were included in this cohort. 4787 (21·6%) participants were in southern Europe, 4866 (22·0%) were in central-western Europe, 3925 (17·7%) were in northern Europe, 3090 (13·9%) were in central-eastern Europe, and 5451 (24·6%) were in eastern Europe. During 222 402 person-years of follow-up, 1705 (7·7%) participants had at least one AIDS-defining illness, including 480 (28·2%) who died of an AIDS-related cause. The overall incidence rate of initial AIDS-defining illnesses was 7·7 per 1000 person-years of follow-up (95% CI 7·3-8·0). The incidence of AIDS-defining illnesses declined across all regions, with the largest absolute decline observed in eastern Europe, where the incidence rate fell from 115·1 (75·8-174·9) per 1000 person-years of follow-up in 2003 to 15·7 (10·5-23·4) per 1000 person-years of follow-up in 2013. In multivariable analysis, the incidence rate ratio of AIDS-defining illnesses over the observation period was 2·59 (95% CI 2·13-3·15) in eastern Europe versus central-western Europe. Other factors associated with AIDS-defining illnesses were HIV acquisition via injecting drug use, CD4 count less than 500 cells per μL, more recent CD4 cell nadir, interrupted or discontinued antiretroviral therapy (ART), previous AIDS-defining illnesses, non-AIDS-defining malignancies, and end-stage liver disease. Opportunistic infections remained predominant over time (>75% of AIDS-defining illnesses). However, a higher proportion of malignancies was observed in 2019-22 versus earlier periods. In eastern Europe, tuberculosis and oesophageal candidiasis accounted for a higher proportion of AIDS-defining illnesses versus in other regions, whereas malignancies were less common. Interpretation The incidence of AIDS-defining illnesses across Europe has decreased during a period of substantial advancements in ART and expanded access. However, the findings highlight continued inequalities in HIV care across Europe and underscore the need for targeted public health strategies to address the persistent high burden of AIDS in eastern Europe. Funding ViiV Healthcare, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb, Merck Sharp & Dohme, Gilead Sciences, the EU's Seventh Framework Programme for Research, Technological Development and Demonstration, the Swiss National Science Foundation, the Danish National Research Foundation, and the International Cohort Consortium of Infectious Disease (RESPOND).