Veterans Aging Cohort Study (VACS) 2.0 Index

Learn about the VACS 2.0 Index, a prognostic tool for assessing mortality risk and health outcomes in individuals living with HIV. Includes components, scoring, clinical applications, and limitations.

Veterans Aging Cohort Study (VACS) 2.0 Index

Calculate VACS 2.0 Index score to assess mortality risk in individuals living with HIV. This updated index includes albumin, BMI, and WBC count for improved prediction.

Demographics

Age (years) *

HIV Status

PositiveNegativeUnknown

Laboratory Values

Hemoglobin (g/dL)

Points: ≥14 (0), 12-13.9 (10), 10-11.9 (22), <10 (38)

FIB-4 (Fibrosis-4 Index)

Points: <1.45 (0), 1.45-3.25 (6), >3.25 (25)

eGFR (mL/min/1.73m²)

Points: >60 (0), 45-59.9 (6), 30-44.9 (8), <30 (26)

Albumin (g/dL) *

Points: ≥3.5 (0), 3.0-3.4 (6), 2.5-2.9 (12), <2.5 (20)

White Blood Cell Count (×10³/μL)

Points: 3.0-12.0 (0), >12.0 (4), 2.0-2.9 (8), <2.0 (12)

Body Mass Index (BMI)

BMI Input Method

Calculate from Height/WeightEnter BMI Directly

Height (cm)

Weight (kg)

Points: 20-29.9 (0), ≥30 (3), 18.5-19.9 (4), <18.5 (8)

Comorbidities

Hepatitis C Virus (HCV) Coinfection (5 points)

Disclaimer: The VACS 2.0 Index is a clinical decision support tool and should not be used as the sole basis for treatment decisions. This calculator is for educational purposes only and does not replace professional medical judgment. Always consider individual patient factors, clinical presentation, and local guidelines when making decisions about patient care. The VACS 2.0 Index was developed using data from the Veterans Health Administration and may have different performance characteristics in other populations.

Veterans Aging Cohort Study (VACS) 2.0 Index

The Veterans Aging Cohort Study (VACS) 2.0 Index is a prognostic tool designed to assess mortality risk among individuals living with HIV. It integrates both HIV-specific and general health biomarkers to provide a comprehensive evaluation of a patient's health status. The VACS 2.0 Index is an updated version that includes albumin, body mass index (BMI), and white blood cell (WBC) count, providing improved prediction of mortality, neurocognitive impairment, and frailty compared to earlier versions.

Purpose: Assess mortality risk and predict health outcomes in individuals living with HIV to guide clinical decision-making, resource allocation, and personalized care planning

VACS 2.0 Index Components

Component	Points	Description
Age	0, 12, or 27	<50 years (0), 50-64 years (12), ≥65 years (27)
CD4 Count (cells/mm³)	0, 6, 10, 28, or 29	≥500 (0), 350-499 (6), 200-349 (6), 100-199 (10), 50-99 (28), <50 (29)
HIV-1 RNA (copies/mL)	0, 7, or 14	<500 (0), 500-99,999 (7), ≥100,000 (14)
Hemoglobin (g/dL)	0, 10, 22, or 38	≥14 (0), 12-13.9 (10), 10-11.9 (22), <10 (38)
FIB-4 Index	0, 6, or 25	<1.45 (0), 1.45-3.25 (6), >3.25 (25)
eGFR (mL/min/1.73m²)	0, 6, 8, or 26	>60 (0), 45-59.9 (6), 30-44.9 (8), <30 (26)
Albumin (g/dL) *	0, 6, 12, or 20	≥3.5 (0), 3.0-3.4 (6), 2.5-2.9 (12), <2.5 (20)
Body Mass Index (BMI) *	0, 3, 4, or 8	20-29.9 (0), ≥30 (3), 18.5-19.9 (4), <18.5 (8)
White Blood Cell Count (×10³/μL) *	0, 4, 8, or 12	3.0-12.0 (0), >12.0 (4), 2.0-2.9 (8), <2.0 (12)
HCV Coinfection	0 or 5	No (0), Yes (5)

* New components in VACS 2.0 Index

Risk Stratification

Low Risk

Score: <20

Interpretation: Lower predicted mortality risk

5-Year Mortality Risk: Approximately 1-3%

Recommendation: Standard care and monitoring. Continue routine follow-up and preventive care. Optimize management of existing comorbidities.

Moderate Risk

Score: 20-39

Interpretation: Moderate predicted mortality risk

5-Year Mortality Risk: Approximately 4-8%

Recommendation: Close monitoring and frequent clinical assessment. Optimize management of all comorbidities. Consider early intervention for complications.

High Risk

Score: 40-59

Interpretation: High predicted mortality risk

5-Year Mortality Risk: Approximately 10-25%

Recommendation: Intensive monitoring and frequent clinical assessment. Aggressive management of all comorbidities. Early intervention for complications. Consider specialist consultations.

Very High Risk

Score: ≥60

Interpretation: Very high predicted mortality risk

5-Year Mortality Risk: Approximately 30-74% (increases with higher scores)

Recommendation: Immediate intensive monitoring and support. Aggressive management of all comorbidities. Early intervention for all complications. Multidisciplinary team approach. Urgent advance care planning.

Clinical Application

When to Use VACS 2.0 Index

Individuals living with HIV for mortality risk assessment
Assessment of overall health status and comorbidity burden
Resource allocation and care planning
Identifying patients at risk for neurocognitive impairment and frailty
Informing treatment decisions and care intensity
Facilitating discussions with patients and families regarding prognosis
Identifying high-risk patients who may benefit from intensive monitoring
Guiding decisions about specialist referrals and multidisciplinary care
Predicting functional decline and health outcomes

How to Calculate

Determine Age: Enter the patient's age. Points: <50 (0), 50-64 (12), ≥65 (27)
Assess HIV Status: If HIV-positive, obtain CD4 count and HIV RNA levels
Obtain Laboratory Values: Collect hemoglobin, FIB-4, eGFR, albumin, and WBC count
Calculate or Enter BMI: Calculate BMI from height and weight, or enter directly
Assess HCV Coinfection: Determine if patient has hepatitis C coinfection
Assign Points: Assign points for each component based on the scoring table
Sum Scores: Add all points to get total VACS 2.0 Index score
Interpret Risk: Classify risk based on total score: Low (<20), Moderate (20-39), High (40-59), Very High (≥60)
Apply Recommendations: Use risk category to guide clinical decision-making and care planning

Key Clinical Features

Enhanced Prediction

The VACS 2.0 Index includes albumin, BMI, and WBC count, providing improved prediction of mortality, neurocognitive impairment, and frailty compared to earlier versions. The C-statistic for all-cause mortality is 0.83, indicating high discrimination.

HIV-Specific Factors

The index includes HIV-specific factors (CD4 count, HIV RNA) that are particularly relevant for HIV-positive individuals, allowing for more accurate risk assessment in this population.

Comprehensive Biomarkers

The index incorporates readily available laboratory markers (hemoglobin, FIB-4, eGFR, albumin, WBC) and anthropometric measures (BMI) that reflect organ function, nutritional status, and disease severity.

Multiple Outcomes

The VACS 2.0 Index predicts not only mortality but also neurocognitive impairment, frailty, and functional decline, making it useful for comprehensive health assessment in people with HIV.

Pathophysiology

Mortality Risk in HIV

People living with HIV face increased mortality risk due to both HIV-related complications and non-AIDS-defining conditions. The VACS 2.0 Index integrates multiple biomarkers to capture the complex interplay between immune function, organ dysfunction, nutritional status, and inflammation.

The addition of albumin, BMI, and WBC count in VACS 2.0 enhances the index's ability to predict mortality, particularly from AIDS-related causes, liver disease, respiratory conditions, and non-AIDS-defining cancers. These markers also correlate with neurocognitive function and frailty, making the index useful for identifying patients at risk for functional decline.

Why These Biomarkers?

The VACS 2.0 Index components were selected based on their association with mortality and health outcomes:

Age is a fundamental risk factor for mortality and age-related conditions
CD4 count and HIV RNA reflect immune function and viral control
Hemoglobin indicates oxygen-carrying capacity and overall health
FIB-4 assesses liver fibrosis and liver disease severity
eGFR evaluates kidney function and chronic kidney disease
Albumin reflects nutritional status, liver function, and chronic disease burden
BMI indicates nutritional status and body composition
WBC count reflects immune function, inflammation, and infection risk
HCV coinfection increases risk of liver disease and mortality

Important Limitations

• The VACS 2.0 Index is a clinical tool and should not be used in isolation
• Assessment requires clinical judgment and experience
• Should be interpreted in the context of complete clinical picture
• Requires correlation with patient history, physical examination, laboratory values, and imaging
• The index was developed using data from the Veterans Health Administration and may have different performance characteristics in other populations
• Not a substitute for clinical judgment or comprehensive evaluation
• Local guidelines and institutional protocols should be considered
• Results may vary based on patient population, clinical setting, and available treatments
• The VACS 2.0 Index predicts mortality risk but does not account for quality of life or functional outcomes in detail
• Consider other factors such as social support, access to care, and treatment adherence when making clinical decisions
• HIV-specific components are only applicable to HIV-positive patients
• Laboratory values should be recent and reflect current clinical status
• The index is primarily validated for people with HIV and may have limited applicability to HIV-negative individuals
• Scores should be interpreted in the context of antiretroviral therapy adherence and response

The Veterans Aging Cohort Study (VACS) 2.0 Index represents a significant advancement in prognostic assessment for individuals living with HIV. This comprehensive tool integrates multiple biomarkers and clinical parameters to provide a nuanced evaluation of mortality risk, health status, and potential for adverse outcomes. Developed through extensive research within the Veterans Health Administration, the VACS 2.0 Index builds upon earlier versions by incorporating additional biomarkers that enhance its predictive accuracy and clinical utility.

Historical Context and Development

The VACS Index was originally developed to address the need for accurate mortality prediction in people living with HIV. As antiretroviral therapy became more effective and HIV transitioned from an acute fatal disease to a chronic manageable condition, clinicians recognized the importance of understanding long-term health outcomes and mortality risk. The original VACS Index incorporated age, CD4 count, HIV RNA viral load, hemoglobin, FIB-4 (a liver fibrosis marker), estimated glomerular filtration rate (eGFR), and hepatitis C virus (HCV) coinfection status.

The evolution to VACS 2.0 Index represented a refinement based on emerging evidence that certain additional biomarkers could improve prediction accuracy. Research demonstrated that albumin, body mass index (BMI), and white blood cell (WBC) count provided independent prognostic information beyond the original components. The inclusion of these markers has enhanced the index's ability to predict not only mortality but also neurocognitive impairment, frailty, and functional decline—outcomes of particular concern in the aging HIV population.

Components of the VACS 2.0 Index

The VACS 2.0 Index incorporates ten distinct components, each contributing points to the total score based on specific thresholds. Understanding each component and its clinical significance is essential for proper interpretation of the index.

Age

Age serves as a fundamental risk factor in the VACS 2.0 Index, reflecting the cumulative impact of aging on health outcomes. The index assigns points based on age categories: no points for individuals under 50 years, 12 points for those aged 50-64 years, and 27 points for those 65 years and older. This stratification recognizes that advanced age independently increases mortality risk, even in the context of well-controlled HIV infection. The aging HIV population faces unique challenges, including accelerated aging processes, increased prevalence of non-AIDS-defining comorbidities, and higher rates of polypharmacy.

CD4 Count

CD4 T-lymphocyte count remains one of the most important indicators of immune function in people with HIV. The VACS 2.0 Index assigns points based on CD4 count thresholds: no points for counts of 500 cells/mm³ or higher, 6 points for counts between 350-499 or 200-349, 10 points for counts between 100-199, 28 points for counts between 50-99, and 29 points for counts below 50 cells/mm³. Lower CD4 counts indicate more advanced immune suppression and are associated with increased risk of opportunistic infections, AIDS-defining illnesses, and mortality. Even in the era of effective antiretroviral therapy, CD4 count recovery may be incomplete in some individuals, and low baseline CD4 counts can have long-term implications for health outcomes.

HIV-1 RNA Viral Load

HIV-1 RNA viral load measurement reflects the degree of viral replication and the effectiveness of antiretroviral therapy. The index assigns no points for viral loads below 500 copies/mL (indicating viral suppression), 7 points for viral loads between 500-99,999 copies/mL, and 14 points for viral loads of 100,000 copies/mL or higher. Undetectable or very low viral loads are associated with better immune function, reduced inflammation, and improved long-term outcomes. High viral loads indicate uncontrolled HIV replication, which contributes to immune activation, chronic inflammation, and increased risk of both AIDS-defining and non-AIDS-defining conditions.

Hemoglobin

Hemoglobin level serves as a marker of oxygen-carrying capacity and overall health status. The VACS 2.0 Index assigns points based on hemoglobin thresholds: no points for levels of 14 g/dL or higher, 10 points for levels between 12-13.9 g/dL, 22 points for levels between 10-11.9 g/dL, and 38 points for levels below 10 g/dL. Anemia is common in people with HIV and can result from multiple mechanisms, including chronic disease, bone marrow suppression, nutritional deficiencies, and medication effects. Low hemoglobin levels are associated with fatigue, reduced exercise capacity, and increased mortality risk.

FIB-4 Index

The Fibrosis-4 (FIB-4) index is a non-invasive marker of liver fibrosis calculated from age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count. The VACS 2.0 Index assigns no points for FIB-4 values below 1.45 (indicating minimal fibrosis), 6 points for values between 1.45-3.25 (indicating moderate fibrosis risk), and 25 points for values above 3.25 (indicating advanced fibrosis or cirrhosis). Liver disease represents a significant cause of morbidity and mortality in people with HIV, particularly those with HCV coinfection, alcohol use, or non-alcoholic fatty liver disease. Elevated FIB-4 scores suggest progressive liver damage and increased risk of liver-related complications.

Estimated Glomerular Filtration Rate (eGFR)

eGFR reflects kidney function and is calculated using serum creatinine, age, sex, and race. The VACS 2.0 Index assigns no points for eGFR values above 60 mL/min/1.73m², 6 points for values between 45-59.9, 8 points for values between 30-44.9, and 26 points for values below 30 mL/min/1.73m². Chronic kidney disease is common in people with HIV and can result from HIV-associated nephropathy, medication toxicity, diabetes, hypertension, or other causes. Reduced kidney function is associated with increased cardiovascular risk, medication dosing challenges, and mortality.

Albumin

Albumin, a key component newly added in VACS 2.0, serves as a marker of nutritional status, liver synthetic function, and overall health. The index assigns no points for albumin levels of 3.5 g/dL or higher, 6 points for levels between 3.0-3.4 g/dL, 12 points for levels between 2.5-2.9 g/dL, and 20 points for levels below 2.5 g/dL. Low albumin levels (hypoalbuminemia) can result from malnutrition, chronic inflammation, liver disease, kidney disease, or protein-losing conditions. Albumin has emerged as particularly important in predicting frailty, cognitive impairment, and functional decline in older adults with HIV, making it a valuable addition to the index.

Body Mass Index (BMI)

BMI, another new component in VACS 2.0, provides information about nutritional status and body composition. The index assigns no points for BMI values between 20-29.9 kg/m², 3 points for BMI of 30 kg/m² or higher (obesity), 4 points for BMI between 18.5-19.9 kg/m² (underweight), and 8 points for BMI below 18.5 kg/m² (severe underweight). Both extremes of BMI are associated with adverse outcomes. Low BMI may indicate malnutrition, wasting, or chronic disease, while high BMI may contribute to metabolic complications, cardiovascular disease, and functional limitations. The relationship between BMI and outcomes in HIV is complex, as some studies suggest that slightly higher BMI may be protective in certain contexts, while severe obesity clearly increases risk.

White Blood Cell Count

WBC count, the third new component in VACS 2.0, reflects immune function, inflammation, and infection risk. The index assigns no points for WBC counts between 3.0-12.0 × 10³/μL (normal range), 4 points for counts above 12.0 × 10³/μL (leukocytosis), 8 points for counts between 2.0-2.9 × 10³/μL (leukopenia), and 12 points for counts below 2.0 × 10³/μL (severe leukopenia). Abnormal WBC counts can indicate infection, medication toxicity, bone marrow suppression, or other hematologic abnormalities. Leukopenia increases infection risk, while leukocytosis may indicate active infection or inflammation.

Hepatitis C Virus (HCV) Coinfection

HCV coinfection status contributes 5 points to the VACS 2.0 Index when present. HCV coinfection is common in people with HIV, particularly those with a history of injection drug use. Coinfection accelerates liver disease progression, increases risk of cirrhosis and hepatocellular carcinoma, and contributes to increased mortality. The availability of highly effective direct-acting antiviral agents has transformed HCV treatment, but coinfection remains an important prognostic factor, particularly in individuals with advanced liver disease or those who have not achieved HCV cure.

Scoring and Risk Stratification

The VACS 2.0 Index generates a total score by summing points from all applicable components. The total score ranges from 0 to over 100, with higher scores indicating greater mortality risk. Risk stratification divides scores into four categories: low risk (score less than 20), moderate risk (score 20-39), high risk (score 40-59), and very high risk (score 60 or higher).

Research has demonstrated strong correlation between VACS 2.0 Index scores and actual mortality outcomes. For example, a score of 40 corresponds to approximately 6% predicted 5-year mortality, while a score of 100 corresponds to approximately 74% predicted 5-year mortality. This wide range of predicted outcomes highlights the index's ability to discriminate between different risk levels and identify individuals who may benefit from more intensive monitoring and intervention.

Clinical Applications

The VACS 2.0 Index serves multiple important functions in clinical practice. Its primary application is mortality risk assessment, helping clinicians and patients understand prognosis and make informed decisions about care intensity and goals. The index can inform discussions about advance care planning, help identify patients who may benefit from palliative care consultation, and guide decisions about resource allocation and care coordination.

Beyond mortality prediction, the VACS 2.0 Index has demonstrated utility in predicting other important outcomes. Higher scores are associated with increased risk of neurocognitive impairment, making the index useful for identifying patients who may benefit from cognitive screening and intervention. The index also correlates with frailty, a syndrome characterized by decreased physiologic reserve and increased vulnerability to stressors. Frailty in people with HIV is associated with functional decline, falls, hospitalization, and mortality.

The index can guide clinical decision-making in several ways. Patients with high scores may benefit from more frequent monitoring, comprehensive geriatric assessment, medication review to reduce polypharmacy, and interventions to address modifiable risk factors. The index can also inform decisions about specialist referrals, with high-scoring patients potentially benefiting from multidisciplinary care teams including geriatricians, nutritionists, physical therapists, and social workers.

Integration with Clinical Care

Effective use of the VACS 2.0 Index requires integration into routine clinical care rather than isolated calculation. The index should be calculated periodically, with frequency depending on clinical context. For stable patients with well-controlled HIV, annual calculation may be appropriate, while patients with active medical issues or recent changes in health status may benefit from more frequent assessment.

Interpretation of the index requires consideration of the clinical context. A high score in a patient with acute illness may reflect temporary factors that could improve with treatment, while a high score in a stable outpatient may indicate more chronic and persistent risk factors. Clinicians should also consider factors not captured by the index, such as social support, access to care, treatment adherence, substance use, mental health, and patient preferences.

The index can serve as a starting point for discussions with patients and families about prognosis and care goals. These conversations should be conducted with sensitivity and respect for patient autonomy, recognizing that prognostic information is one factor among many in decision-making. Some patients may find prognostic information helpful in planning for the future, while others may prefer to focus on day-to-day management.

Modifiable Risk Factors

While many components of the VACS 2.0 Index reflect factors that cannot be easily modified (such as age or genetic predisposition), several components represent potentially modifiable risk factors. Understanding these modifiable factors can guide interventions to improve outcomes.

HIV RNA viral load represents a highly modifiable factor through effective antiretroviral therapy. Achieving and maintaining viral suppression is associated with improved immune function, reduced inflammation, and better long-term outcomes. CD4 count recovery, while not always complete, can occur with effective antiretroviral therapy, particularly when initiated early in the course of infection.

Anemia may be modifiable through treatment of underlying causes, nutritional support, or medication adjustments. Liver disease, reflected in FIB-4 scores, may be improved through HCV treatment, alcohol cessation, weight management, and management of metabolic factors. Kidney function may be preserved or improved through blood pressure control, diabetes management, avoidance of nephrotoxic medications, and appropriate medication dosing.

Nutritional status, reflected in albumin and BMI, may be improved through nutritional assessment and support, treatment of underlying conditions contributing to malnutrition, and management of obesity when present. WBC abnormalities may improve with treatment of underlying infections, medication adjustments, or management of other contributing factors.

HCV coinfection is now highly treatable with direct-acting antiviral agents, and achieving sustained virologic response (cure) can improve liver function and reduce liver-related complications. However, the VACS 2.0 Index may continue to reflect the impact of prior liver damage even after HCV cure.

Limitations and Considerations

While the VACS 2.0 Index provides valuable prognostic information, it is important to recognize its limitations. The index was developed and validated primarily in the Veterans Health Administration population, which may limit generalizability to other populations. Veterans may differ from the general population in terms of demographics, comorbidities, healthcare access, and other factors that could influence outcomes.

The index provides population-level risk estimates rather than individual-level predictions. A patient with a high score may still have a favorable outcome, while a patient with a low score may experience adverse outcomes. The index should not be used as the sole basis for clinical decisions but rather as one tool among many in comprehensive clinical assessment.

Laboratory values used in the index should be recent and reflect current clinical status. Values obtained during acute illness may not accurately reflect baseline risk. The index requires accurate input values, and errors in measurement or calculation can lead to inaccurate scores.

Some components of the index may not be applicable to all patients. For example, HIV-specific components (CD4 count, HIV RNA) are only relevant for HIV-positive individuals. In HIV-negative individuals, these components would not contribute to the score, potentially limiting the index's utility in this population.

The index does not account for all factors that may influence outcomes, such as social determinants of health, mental health, substance use, treatment adherence, access to care, or quality of life. These factors may be as important as the biomarkers included in the index and should be considered in clinical decision-making.

Temporal changes in the index components may not be immediately reflected in outcomes. For example, improvements in CD4 count or viral suppression may take time to translate into improved outcomes, while the index may reflect current status rather than trajectory.

Research and Validation

The VACS 2.0 Index has been extensively validated in multiple cohorts, demonstrating strong discrimination for all-cause mortality with a C-statistic of 0.83, indicating high predictive accuracy. The index has been shown to predict mortality from various causes, including AIDS-related causes, liver disease, respiratory conditions, and non-AIDS-defining cancers.

Research has also demonstrated the index's utility in predicting non-mortality outcomes. Studies have shown associations between VACS 2.0 Index scores and neurocognitive impairment, with higher scores predicting worse cognitive function. The inclusion of albumin in the index has been particularly important for predicting frailty and cognitive outcomes, as albumin reflects nutritional status and chronic disease burden that may not be captured by other markers.

The index has been validated in diverse populations, including different racial and ethnic groups, though some studies suggest that performance may vary across populations. Ongoing research continues to refine the index and explore its utility in different clinical contexts and populations.

Future Directions

As research continues, the VACS 2.0 Index may be further refined or expanded. Potential areas for future development include incorporation of additional biomarkers, such as markers of inflammation, coagulation, or cardiovascular risk. The index might also be adapted for specific populations or clinical contexts, such as different age groups, treatment-naive versus treatment-experienced patients, or specific comorbidity profiles.

Integration of the index into electronic health records could facilitate routine calculation and tracking over time, allowing for assessment of trajectory and response to interventions. Machine learning approaches might enhance the index's predictive accuracy or identify novel combinations of factors that improve risk prediction.

Research exploring the index's utility in guiding specific interventions, such as intensive monitoring programs, preventive care, or treatment modifications, could further enhance its clinical value. Understanding how changes in index components over time relate to outcomes could provide insights into the effectiveness of interventions and help guide clinical management.