Combining Charlson comorbidity and VACS indices improves prognostic accuracy for all-cause mortality for patients with and without HIV in the Veterans Health Administration

Abstract

Introduction: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index.

Methods: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age </≥65 years, race/ethnicity, and CCI score). We then applied VACS-CCI in PWH and compared its accuracy to age, VACS Index 2.0, CCI and VACS-CCI with CD4 and HIV RNA added.

Results: The analytic sample consisted of 6,588,688 PWoH and 30,539 PWH. Among PWoH/PWH, median age was 65/55 years; 6%/3% were women; 15%/48% were Black and 5%/7% Hispanic. VACS-CCI provided the best discrimination (C-statistic = 0.81) with excellent calibration (predicted and observed mortality largely overlapped) overall and within subgroups. When VACS-CCI was applied to PWH it demonstrated similar discrimination as VACS Index 2.0 (C-statistic = 0.77 for both) but superior calibration among those with CD4 < 200. Discrimination was improved when CD4 and HIV RNA were added VACS-CCI (C-statistic = 0.79). Liver and kidney disease, congestive heart failure, malignancy, and dementia were negatively associated with CD4 (p-trends all <0.0001).

Discussion: Among PWH and PWoH in VA care, age alone weakly discriminates risk of mortality. VACS Index 2.0, CCI, and VACS-CCI all provide better discrimination, but VACS-CCI is more consistently calibrated. The association of comorbid diseases with lower CD4 underscores the likely role of HIV in non-AIDS conditions. Future work will include adding CD4 and HIV RNA to VACS-CCI and validating it in independent data.

Keywords: Charlson Comorbidity Index; HIV; VACS Index; mortality; prediction.

Figure 1

Model fit (AIC) and discrimination (c-statistic) from series of models for 10-year, all-cause mortality using Cox regression in development sample.

Figure 2

Observed (open circles) and predicted (solid line) 10-year, all-cause mortality as a function of VACS-CCI score. 95% confidence intervals for observed mortality are very narrow and may be difficult to discern.

Figure 3

VACS-CCI predicted mortality based on general (PWoH) sample, 2007–2017.

Figure 4

Among PWH, observed (open circles) and predicted (solid line) 10-year, all-cause mortality as a function of VACS-CCI and VACS Index 2.0 risk scores. 95% confidence intervals for observed mortality are very narrow and may be difficult to discern.

Figure 5

Charlson comorbidity components by CD4 level among PWH.