The VACS Index
Frequently Asked Questions and
Summary of Evidence as of February, 2016
What is the VACS Index?
The Veterans Aging Cohort Study Index (VACS Index) creates a score by summing pre-assigned points
for age, routinely monitored indicators of HIV disease (CD4 count and HIV-1 RNA), and general
indicators of organ system injury including hemoglobin, platelets, aspartate and alanine transaminase
(AST and ALT), creatinine, and viral hepatitis C infection (HCV) (Table 1) (1).. The score is weighted to
indicate increasing risk of all-cause mortality with increasing score. The score can be used to estimate
risk of all-cause mortality using a conversion factor.(2). A calculator, summary of validation work to date,
and a clinical interpretation of VACS Index scores can be found at http://vacs.med.yale.edu.
Table 1. The VACS Index
Component
Age (years)
Level
<50
50 to 64
> 65
CD4 (cells/mm3)
> 500
350 to 499
200 to 349
100 to 199
50 to 99
< 50
0
6
6
10
28
29
HIV-1 RNA (copies/ml)
< 500
500 to 99,999
> 1x105
0
7
14
Hemoglobin (g/dL)
> 14
12 to 13.9
10 to 11.9
< 10
0
10
22
38
FIB-4
< 1.45
1.45 to 3.25
> 3.25
0
6
25
eGFR (mL/min)
> 60
45 to 59.9
30 to 44.9
< 30
0
6
8
26
Hepatitis C Co-Infection
Points
0
12
27
5
What does the VACS Index Do?
The VACS Index predicts all-cause mortality,
cause-specific mortality, and other outcomes
in those living with HIV infection. If one
assumes that uninfected patients have no
HIV-1 RNA titer and a CD4 cell count at or
above 500 cells/mm3, it also predicts all-cause
mortality and hospitalization among those
without HIV infection. The index responds to
important changes in risk related to treatment
and health behaviors. It improves accuracy of
provider assessment (clinical judgment) of
mortality risk. Specific evidence is bulleted
below.
 It predicts mortality among those with
HIV infection The Index was developed in
veteran patients(1) and its accuracy has
been validated in other patient populations
in North America and Europe(1, 2). It
discriminates risk of mortality more
effectively than an index restricted to CD4
count, HIV-1 RNA and age (Restricted
Index) especially among those with
undetectable HIV-1 RNA and those 50 or
more years of age(1, 2).The accuracy of the
Index for predicting mortality among HIV
infected individuals in treatment meets or
exceeds the accuracy reported for indices
currently used in clinical practice(3-5).
Further, its accuracy is independent of
length of time on antiretroviral treatment and
is robust among important patient subgroups
including women, people of color, those with
HCV coinfection, and those over 50 years of
age(1, 2). It is also predicts mortality among
young active duty military, relatively free of
comorbid disease(6) and among those
initiating salvage antiretroviral therapy after
becoming resistant to at least two classes of
antiretroviral therapy(7).
 It predicts mortality among uninfected individuals If you assume that those without HIV infection
have no HIV-1 RNA (i.e. 0 points) and a CD4 cell count above 500 cells/mm3 (i.e. 0 points), the VACS
Index also predicts mortality among those without HIV infection. This has been shown for 30-day
mortality from MICU admission(8) and for long term (median of 5 years) mortality(9).
 It predicts outcomes after admission for bacterial pneumonia Among HIV infected and uninfected
(age 50+ years) veterans the index predicts 30-day mortality, length of stay, and readmission(10).
 It is associated with frailty Frailty is defined as decreased ability to recover from additional injury(11).
The index is associated with increased risk for a number of adverse outcomes including mortality,
hospitalization, geriatric syndromes (falls, fragility fractures, and cognitive decline) and is strongly
associated with chronic inflammation. The VACS Index is correlated with markers of chronic
inflammation, microbial translocation, and hypercoagulability (cystatin C, TNF alpha, IL-6, soluble
CD14, soluble CD163, and D-dimer)(12-14), with measures of functional performance(15) and
sarcopenia(16), and with multiple measures of neuro-cognitive performance(17). The VACS Index
predicts morbidity including hospitalization, medical intensive care unit admission(18), and fragility
fractures(19). It is also associated with autonomic neuropathy(20). It is an effective measure of
physiologic frailty (21, 22). Few individuals demonstrated frailty based on the adapted frailty related
phenotype(23).When compared with an adapted version of the frailty related phenotype, the VACS
Index more accurately predicted both all-cause mortality and hospitalization among HIV infected and
uninfected individuals. Of note, the approach to frailty employed by the VACS Index is more attuned to
the Rockwood conceptualization(24) of frailty as accumulation of deficits than that of Fried(25) which
describes a clinical syndrome.
 It responds to important changes in health and health behaviors VACS Index scores change in
response to antiretroviral initiation(26) and interruption(6), and discriminate among levels of ART
adherence(26). VACS Index scores differ by level of smoking, alcohol consumption and
hypertension(27, 28). VACS Index scores predict weight gain in the first 12 months after ART
initiation(29). When levels of alcohol consumption change among HIV infected subjects, the index
score also changes. Similarly, when HIV infected subjects in treatment for substance abuse have
positive urine toxicology screens, their scores are higher than when the same subjects have negative
toxicology screens. (Papers reporting responsiveness of the VACS Index to changes in alcohol and
substance use are in preparation).
 It is accurate in a wide range of patient populations VACS Index predicts all-cause mortality in a
wide range of HIV infected populations including those first initiating ART(30), after the first year of
ART(1, 2), among highly treatment experienced patients(7) and among young military recruits(6). It
predicts well among men and women, older and younger subjects, those with and without HCV coinfection, and those with and without HIV-1 viral suppression(1, 2, 7).
 It predicts cause-specific mortality VACS Index predicts both HIV and non-HIV associated mortality
better than an index restricted to CD4 count, HIV-1 RNA, and age(1). It predicts cardiovascular
mortality as accurately as it predicts all-cause mortality(31).
 It improves accuracy of provider assessment of risk Although providers have results of routine
clinical biomarkers included in the VACS Index available at the time of assessment, provider
assessments may not accurately incorporate the implications of these tests for risk of mortality. For
both veterans with and without HIV infection, provider assessments of severity of illness (“How sick is
this patient?”) and risk of 10 year mortality were substantially less accurate than estimates based on
the VACS Index and were considerably improved when combined with the VACS Index(32). Thus, the
VACS Index adds important insight to provider assessment of severity of illness and risk of mortality.
How modifiable is the VACS Index?
Over the course of the first 12 months of ART, CD4 and HIV-1 RNA change dramatically, but so do level
of hemoglobin, FIB 4, and, to a lesser extent, eGFR. Values also differ by level of adherence to ART, by
smoking, by alcohol, by HCV status, by number of non-ARV medications, and by physical function. As
mentioned above under responsiveness to changes in health and health behaviors, VACS Index scores
rise during negative health behaviors (alcohol and substance use) and fall when these behaviors are
diminished or extinguished. It is likely that successful interventions in any or all of these domains would
alter the VACS Index Score. (A paper summarizing how VACS Index scores change over the first 12
months of ART using data from NA-ACCORD and ART-CC combined is under review.)
Why is this useful?
Potential applications of the VACS Index include mechanistic and clinical research as well as clinical
care.

Translational Research The VACS Index can inform mechanistic studies focused on long term
pathophysiologic effects of aging with HIV. We have demonstrated the stronger association of
the VACS Index to markers of chronic inflammation and hypercoagulability compared with an
Index restricted to age, CD4 count and HIV-1 RNA(12) and when compared with the
Framingham Index(14). Of note, hemoglobin was the single index component most associated
with D-dimer(12). The strong and independent association of liver injury (measured by FIB 4)
and of anemia (measured by hemoglobin) with health outcomes among HIV infected individuals
on ART is consistent with the theory that early changes after HIV infection undermine the gut
mucosa and expose the liver to a greater burden of microbial products contributing to
progressive liver dysfunction and chronic inflammation(33).

Clinical Research Observational studies frequently struggle with issues around confounding by
indication when studying post marketing treatment effects. The VACS Index could be used as a
powerful adjustment either directly or as part of a propensity score. Randomized trials often need
to insure that the arms of the trial are equally at risk for the observed outcome (i.e., that
randomization worked).The VACS Index offers a means of making this determination, accounting
for a number of important predictors of major clinical outcomes. Conversely, randomization could
be stratified by VACS Index score. Finally, change in VACS Index score could be used as a
response measure for a number of diverse interventions, thereby allowing assessment of their
comparative effectiveness.

Clinical Care Potential applications include estimating short and long term risk of morbidity and
mortality, estimating life expectancy, quantifying response to interventions, and detecting HIV
and non-HIV treatment toxicity. The index may also be useful in motivating behavior change and
prioritizing treatment. For example, the VACS Index might help inform medical decision making
regarding hospitalization, admission to the Medical Intensive Care Unit, timing of discharge, and
discharge planning. The index might also inform decisions regarding frequency of clinical followup, elective surgical procedures, nursing home placement, and other case management issues.
While the index does not include all potentially important targets for intervention (smoking, CVD
risk factors, alcohol intake, ART adherence, etc.), it responds to differences in these factors and
therefore reflects their effects. We are currently developing an extension of the VACS Index
Calculator app (http://vacs.med.yale.edu) that would support use of the index to motivate health
behavior change.
How are others using the VACS Index?
 Research Two NIH funded, alcohol intervention trials are underway which include the VACS
Index as an outcome. The AIDS Clinical Trials Group has begun to use the VACS Index in
randomized trials (34) Independent groups have begun to use the VACS Index as a measure of
frailty or severity of illness(13, 14, 17, 20, 21, 35-41).

Clinical Care As of February 2016, the VACS Index Risk Calculator (link above) has been
accessed 76,000 times since March of 2013 and most of these represent repeated use (first time
visitors 5,400). Fenway Healthcare System in Boston is exploring using the VACS Index to
identify patients for intensive case management. The San Francisco General Hospital HIV clinic
has incorporated the VACS Index scoring into its electronic medical record and is using it in
patient management. In Italy, the VACS Index is calculated on every patient seen at the
University of Modena Metabolic Clinic (a clinic of over 4000 patients) using an automated
application. A group in Italy (FB Communication) is developing an Italian language app for the
VACS Index for use in Italy.
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