Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late for HIV diagnosis – results from the Icona cohort in Italy, 2009-2022

Background: Limited data are available on long-term outcomes in recent years for late HIV diagnosis (LD). Methods: All HIV-positive subjects enrolled in Icona Cohort in 2009-2022 starting ART within 4-months from diagnosis were included and divided into:1) pre-ART CD4 count≥350/mm3 without AIDS (non-LD), 2) pre-ART CD4 count<350/mm3 without AIDS (LD-Asymptomatic), 3) with AIDS events pre-ART (LD-AIDS). Estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure (TF) were evaluated. Results: 6,813 participants: 2,448 non-LD, 3,198 LD-Asymptomatic, and 1,167 LD-AIDS, 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD compared to non-LD (p<0.001), and within the former, for LD-AIDS over LD-Asymptomatic (p<0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD aHR=5.51, p<0.001), and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR=4.42, p<0.001), AIDS-related (aSHR=16.86, p<0.001) and not AIDS-related mortality (aSHR=1.74, p=0.022) compared to the rest of the late presenters. Among short-term survivors LD-AIDS, the long-term mortality was mediated by the lack of immune-recovery at 2-years. LD compared to non-LD, and particularly among the former, LD-AIDS over LD-Asymptomatic, showed also a greater risk of TF. Conclusions: In recent years, LD subjects, particularly AIDS-presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.