The Validation of Mortality Risk Indexes for Predicting Long-Term Outcomes in People Living with HIV in a Spanish Cohort (eVIHa)

<b>Background/Objectives</b>: Having access to antiretroviral therapy (ART) has altered the health status of people living with HIV (PLHIV) to that of having a chronic condition, with a greater life expectancy. The development of the Veterans Aging Cohort Study (VACS) Index has allowed for the prediction of 5-year mortality in PLHIV, using both HIV-related and non-HIV-related markers. The modified Charlson Index describes the comorbidity burden and is indicated to predict 10-year mortality. This study validates the Veterans Aging Cohort Study (VACS) Index 1.0 and the modified Charlson Index in a contemporary European cohort, with the aim of better predicting mortality. <b>Methods</b>: An observational, multicenter study was conducted using data from the eVIHa cohort in the Balearic Islands (Spain) from 2000 to 2023. The VACS Index 1.0 and the modified Charlson Index were calculated. Model discrimination was assessed using Harrell's C-statistic, and observed mortality was estimated using Kaplan-Meier analysis. <b>Results</b>: Of 6913 eligible PLHIV, 4480 (64.8%) had sufficient data for VACS Index calculation and were included in the primary analysis. The excluded group (N = 2433) had significantly higher mortality (27.7% vs. 9.4%) and a greater proportion of people who inject drugs. In the analyzed cohort, the VACS Index 1.0 showed good discrimination for 5-year all-cause mortality (C-statistic: 0.759), outperforming the modified Charlson Index (C-statistic: 0.729). Discrimination was the highest for deaths from liver disease (C: 0.875) and non-HIV-related infections (C: 0.853). <b>Conclusions</b>: In our analyzed cohort, the VACS Index 1.0 accurately predicted 5-year mortality. However, its performance in populations with higher rates of people who inject drugs and irregular follow-up is unknown and likely to be lower. Clinicians should be aware of these limitations when applying the index in practice.