Burden of advanced HIV disease among antiretroviral therapy-experienced persons with HIV in Italy over the past 20 years

Introduction: Data on the burden of advanced HIV disease (AHD) among people with HIV (PWH) already in care remain limited in high-income settings. Methods: We included all PWH from the Icona Cohort who started ART between 2004 and 2024, with CD4≥200 cells/mm3 and no prior AIDS-defining event (ADE). Probability of AHD (CD4<200 cell/mm3 or ADE) occurring ≥3 months after ART initiation was estimated by Kaplan-Meier curves. In a nested case-control study, AHD cases were matched 1:2 to controls by CD4 nadir, age, and ART duration. Predictors of AHD were evaluated by conditional logistic regression. Mortality risk in cases versus controls was also assessed. Results: Among 9,972 ART-experienced PWH, 429 (4.3%) developed AHD. Incidence was highest during the first year of ART (1.6%) and increased linearly thereafter, with lower rates among more recent ART initiators. In the case-control study, female sex, lower education, unemployment, injecting drugs use, prolonged disengagement from care and suboptimal virologic control were associated with an increased AHD risk. AHD cases exhibited an over 8-fold higher risk of all-cause mortality, particularly within two years post-diagnosis. Conclusions: Although declining, the risk of AHD following ART, remains a concern in Italy. Efforts to improve sustained care engagement, especially among women and socioeconomically vulnerable groups, are critical.