VACS Index score can help identify HIV-positive people most at risk of neurocognitive decline

A combination of simple, routine blood tests may be able to predict which people living with HIV are especially vulnerable to neurocognitive decline, according to US research published in Clinical Infectious Diseases. People with high VACS (Veterans Aging Cohort) Index scores had an increased risk of experiencing a decline in neurocognitive function and were also significantly more likely to develop new neurocognitive problems.

“Changes in VACS Index correspond to changes in neurocognitive function over time in a large, well-characterized HIV-infected cohort,” write the authors.

Despite major advances in treatment and care, neurocognitive impairment (NCI) remains common in people with HIV, occurring in between 30% and 50% of individuals. In most people with HIV this is mild. Nevertheless, even milder forms of impairment can have a negative impact on day-to-day life.



Describes a general decline in physical health and a loss of reserves, most often seen in older people. Frailty leads to a person being less robust and less able to bounce back after an adverse event. A person with frailty may move more slowly, have lost some of their physical strength, have less energy and be less mentally agile. 


A shortage or change in the size or function of red blood cells. These cells carry oxygen to organs of the body. Symptoms can include shortness of breath, fatigue and lack of concentration.


Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.


Relating to the kidneys.


A mental health problem causing long-lasting low mood that interferes with everyday life.

It is therefore important to identify which people are at risk of developing neurocognitive impairment and also those with baseline impairment at high risk of further decline.

The VACS Index was developed as a marker of disease severity in people living with HIV. It is based on the results of blood tests that are performed as part of routine care, such as CD4 count, viral load, renal and liver function, anaemia and hepatitis C screening. A higher VACS Index score has consistently been associated with an increased risk of death in patients, hospitalisation and also diseases usually associated with older age, such as frailty, fragility fracture and low muscle strength.

Now investigators wanted to see if VACS Index score could predict neurocognitive change and incident neurocognitive impairment.

They therefore designed a study involving 655 adults living with HIV receiving care at the University of California, San Diego. Study participants were followed for up to six years.

Three outcomes were investigated:

  • The association between baseline VACS Index score and subsequent neurocognitive change.
  • Whether changes in VACS Index scores over time were correlated with changes in neurocognitive function.
  • Whether VACS Index scores predicted time to incident neurocognitive impairment in people with normal neurocognitive function at baseline.

Participants with major psychiatric disorders or brain injury were excluded from recruitment.

Neurocognitive function was assessed using a comprehensive battery of tests. Initial scores were converted in T scores adjusted for age, education, sex and race. The adjusted T scores were then averaged to obtain global and domain T scores.

Participants had a mean age of 43 years, 83% were male, 60% were white, mean CD4 count was 346 cells/mm3, 67% had an AIDS diagnosis, 61% were taking antiretroviral therapy and 51% had an undetectable viral load. Three-quarters reported a history of substance abuse.

At baseline, 40% were assessed as having neurocognitive impairment. Median VACS Index score was 22. Participants with and without neurocognitive impairment were broadly comparable.

There was no significant association between baseline VACS Index score and neurocognitive change.

However, there was a significant association between higher VACS Index and worse global and domain neurocognitive performance, even after adjusting for potential confounders (p < 0.01).

Higher VACS Index was associated with poorer memory scores in people not taking antiretrovirals (p < 0.01) but not for people taking HIV therapy.

Analysis of the 60% of people with no neurocognitive impairment at baseline showed that higher baseline VACS Index scores were associated with increased chances of developing impairment (p < 0.01). After controlling for factors such as nadir CD4 count and baseline depression this association ceased to be significant. But in the time-dependent analyses, higher VACS Index scores were associated with a significantly increased risk of incident neurocognitive impairment (HR, 1.17; 95% CI, 1.06-1.29, p < 0.01).

Study participants with higher VACS Index scores were significantly more likely to develop neurocognitive impairment compared to those with low (p < 0.01) and moderate (p < 0.01) VACS Index scores. Moreover, people with higher VACS Index scores were also significantly more likely than others to experience neurocognitive decline (p = 0.02).

“Overall, baseline VACS Index scores may not be a good predictor of neurocognitive change in the longer term. Changes in VACS Index scores, however, correspond to changes in neurocognition,” conclude the authors. “Having very high VACS Index scores might indicate a notable increased risk of neurocognitive decline and incident NCI. These findings support the VACS Index as a simple tool for identifying HIV-infected patients who are at high risk of NCI and might warrant further neurocognitive follow-up.”


Marquine MJ et al. The Veterans Aging Cohort Study (VACS) Index and neurocognitive change: a longitudinal study. Clin Infect Dis, online edition. DOI: 10.1093/cid/ciw328, 2016.