Veterans Aging Cohort Study (VACS) 2.0 Index

The VACS 2.0 Index is a prognostic score used to estimate all-cause mortality risk in people with HIV, especially over a 5-year horizon. It is an updated version of the original VACS Index and was designed to improve prediction by combining traditional HIV markers with broader indicators of organ injury and general health. In validation work, the authors concluded that VACS 2.0 can reliably estimate mortality probability at multiple follow-up times among people with HIV in North America.

Why VACS 2.0 was developed

The original VACS Index already performed better than HIV-only models because it included age and biomarkers of end-organ injury rather than relying only on CD4 count and viral load. VACS 2.0 was developed as an update to improve discrimination and calibration further by adding albumin, white blood cell count, and body mass index to the earlier framework. Later papers describing the score note that these non-HIV-specific biomarkers helped the updated index outperform VACS 1.0.

What the index includes

The VACS 2.0 model uses a mix of HIV-specific and general clinical variables. The published supplementary material lists the major inputs as age, CD4 cell count, HIV-1 RNA, hemoglobin, FIB-4, eGFR, hepatitis C status, albumin, white blood cell count, and BMI. These were selected to capture both HIV control and broader physiologic injury affecting liver, kidney, blood, nutrition, and systemic health.

How it is interpreted

The VACS 2.0 output is a continuous score, with higher values indicating worse overall prognosis. The published scoring supplement provides example point values and shows a baseline score of 44 when predictors are set to their median values and hepatitis C is absent. A later validation paper translated score levels into 5-year mortality estimates, including approximately 0.2% at score 10, 1.6% at score 40, 5.9% at score 60, 20.4% at score 80, and 57.2% at score 100.

Performance of VACS 2.0

A major reason VACS 2.0 is important is that it improved on the earlier index in both discrimination and calibration. In the 2022 calibration paper, VACS 2.0 showed better discrimination of all-cause mortality for people with HIV than VACS 1.0, and the authors reported that it could provide validated mortality probabilities across different follow-up times. More recent work also found that the score discriminates some cause-specific mortality outcomes well, particularly deaths attributed to AIDS, liver disease, and respiratory infections.

Strengths

One strength of VACS 2.0 is that it reflects overall physiologic vulnerability, not just HIV disease activity. That matters because many people with HIV now live long enough for non-AIDS comorbidities and organ dysfunction to drive outcomes. The score is also practical because its inputs are generally routine clinical data rather than specialized tests. Studies outside the original VA setting have also used the VACS framework successfully, supporting broader clinical usefulness.

Limitations

The VACS 2.0 Index is a risk-prediction tool, not a diagnostic test, and it should not be used in isolation to make major treatment decisions. Its performance can vary depending on the population and the specific outcome being predicted. For example, the 2024 cause-specific mortality study found stronger discrimination for some causes of death than for others, such as suicide. Also, because it was developed and validated in cohort data, local calibration may matter when applying it to different healthcare systems or patient mixes.

Current role

Today, VACS 2.0 is best viewed as a structured way to summarize multisystem health risk in HIV care. It can support prognosis, research stratification, and population health planning. It has also been studied beyond mortality alone, including associations with hospitalization and functional decline, which suggests that it captures clinically meaningful frailty and comorbidity burden in aging people with HIV.

Bottom line

The VACS 2.0 Index is an updated mortality risk score for people with HIV that improves on the original VACS Index by adding albumin, white blood cell count, and BMI to a model already built on age, HIV measures, and organ injury biomarkers. Its main value is that it provides a more realistic estimate of medium-term mortality risk in modern HIV care by reflecting whole-person health rather than HIV status alone.

References

1. Tate JP, Sterne JAC, Justice AC, et al. Appendix Table 1. VACS Index 2.0 Cox proportional hazards model and score tables. Supplementary appendix to the VACS 2.0 publication.
2. McGinnis KA, Tate JP, Feinstein MJ, et al. Discrimination and Calibration of the Veterans Aging Cohort Study Index 2.0. Clinical Infectious Diseases. 2022.
3. Ambia J, et al. Discrimination of the Veterans Aging Cohort Study Index 2.0 in predicting cause-specific mortality among people with HIV on antiretroviral therapy. Open Forum Infectious Diseases. 2024.
4. Justice AC, Modur SP, Tate JP, et al. Predictive Accuracy of the Veterans Aging Cohort Study Index for Mortality With HIV Infection. JAIDS. 2013. Background on the original VACS framework.
5. Qian Y, et al. Association of the VACS Index with hospitalization among people with HIV in NA-ACCORD. Notes that VACS 2.0 adds albumin, WBC, and BMI and has better discrimination than VACS 1.0.
6. Reddon H, et al. The Veterans Aging Cohort Study (VACS) Index Predicts Mortality in a Young, Healthy HIV Population Starting Highly Active Antiretroviral Therapy. External-use context for the VACS framework.