Background
Despite the rising burden of advanced HIV disease (AHD) among persons with HIV (PWH) engaged in care in low-income countries, the dimension, features, and prognosis of this reclassified “neglected disease” in resource-rich settings have not been thoroughly evaluated.
Methods
PWH enrolled in the Icona Foundation Study cohort with a first diagnosis of AHD (CD4<200cells/mm3 or AIDS-defining event [ADE]) between January 1,2004 and December 31, 2023 were included. Participants were classified as having either a prevalent AHD (pAHD: AHD diagnosed at the time of starting ART) or an incident AHD (iAHD: AHD diagnosed >3 monthsafter starting ART) -the main exposure of interest. We also used an alternative 4-way exposure group to disentangle the effect of ADE. Temporal trends and demographic/clinical characteristics were described at the time of AHD definition. The cumulative risk of all-cause mortality from the time of AHD definition was compared by exposure groups by Kaplan-Meier curves and Cox regression models after controlling for confounding.
Results
Overall, 5,436 PWH with a median age of 45 years, a first diagnosis of AHD contributing to 31,788 PYFU were included: 4,671 newly HIV-diagnosed (pAHD) and 765 already in care (iAHD), where 34% and 32% respectively fulfilled the definition of AHD due to an ADE diagnosis. Compared to pAHD, iAHD were more likely to be female (29% vs. 23%, p=0.001) Italian (84% vs. 72%, p<0.001) and injection drug users (IDU) (23% vs. 8%, p<0.001) . The overall incidence (95%CI) of iAHD was 20.4 (16.8,24.8) per 1,000 PYFU which sharply declined below 12% of total AHD in the last decade (Figure A). Univariable survival analysis showed a significantly increased risk of death in iAHD vs. pAHD (by 10 years: 17.0% (13.8,20.7) vs. 10.7% (9.6,11.9), p<0.001). After adjusting for confounding, the risk of death associated with being iAHD was attenuated but remained 31% higher than that of pAHD, mainly determined by ADE, especially in the iAHD group (Figure B).
Conclusions
Although the incidence of AHD among PWH on ART has significantly reduced over time, the current magnitude of the estimate is of concern. iAHD, compared to pAHD, were of Italian nationality with a more frequent history of IDU and also showed worse clinical outcomes for a given set of risk factors for death. Reasons for the difference in risk, possibly linked to behaviour and style of life, need to be further investigated to prevent AHD after charging in care and to identify AHD before progression to AIDS.