Blood tests to predict neuro-cognitive decline in HIV patients

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mb-114 neurocog declineA combination of simple, routine blood tests may be able to predict which people living with HIV are especially vulnerable to neuro-cognitive decline, according to US research.

People with high VACS (Veterans Aging Cohort) Index scores had an increased risk of experiencing a decline in neuro-cognitive function and were also significantly more likely to develop new neuro-cognitive problems.

“Changes in VACS Index correspond to changes in neuro-cognitive function over time in a large, well-characterised HIV-infected cohort,” write the authors from the HIV Neurobehavioral Research Programme Group, University of California San Diego.

Despite major advances in treatment and care, neuro-cognitive 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.

It is therefore important to identify which people are at risk of developing neuro-cognitive 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 neuro-cognitive change and incident neuro-cognitive 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 neuro-cognitive change; whether changes in VACS Index scores over time were correlated with changes in neuro-cognitive function; and whether VACS Index scores predicted time to incident neuro-cognitive impairment in people with normal neuro-cognitive function at baseline.

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

Neuro-cognitive 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 neuro-cognitive impairment. Median VACS Index score was 22. Participants with and without neuro-cognitive impairment were broadly comparable. There was no significant association between baseline VACS Index score and neuro-cognitive change.
However, there was a significant association between higher VACS Index and worse global and domain neuro-cognitive 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 neuro-cognitive 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 neuro-cognitive 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 neuro-cognitive 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 neuro-cognitive decline (p = 0.02).

“Overall, baseline VACS Index scores may not be a good predictor of neuro-cognitive change in the longer term. Changes in VACS Index scores, however, correspond to changes in neuro-cognition,” conclude the authors. “Having very high VACS Index scores might indicate a notable increased risk of neuro-cognitive 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 neuro-cognitive follow-up.”

Abstract
Background: The Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immunodeficiency virus (HIV)–infected persons, has been associated with concurrent risk for neurocognitive impairment (NCI). The present study examined whether the VACS Index predicts longitudinal neurocognitive change.
Methods: Participants included 655 HIV-infected persons followed for up to 6 years in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (mean age at baseline, 42.5 years; 83% male; 60% white; AIDS in 67%; median current CD4+ T-cell count, 346/μL; 61% receiving antiretroviral therapy). The VACS Index was calculated through standard methods. Participants completed a comprehensive neurocognitive battery. Neurocognitive status was plotted over time using demographically and practice-adjusted global and domain T scores. NCI was defined by global deficit scores derived from T scores.
Results: Baseline VACS Index scores were not predictive of changes in global T scores during the follow-up period ( P = .14). However, in time-dependent analyses adjusting for covariates, higher VACS Index scores were significantly associated with worse global and domain neurocognitive performance (Ps < .01), as well as increased risk for developing NCI in a subgroup of persons who were neurocognitively normal at baseline (hazard ratio [HR], 1.17; P < .001). We categorized VACS Index scores by quartiles and found that the upper-quartile group was significantly more likely to develop NCI than the lower quartile (HR, 2.16; P < .01) and middle groups (HR, 1.76; P < .01).
Conclusions: Changes in VACS Index scores correspond to changes in neurocognitive function. HIV-infected persons with high VACS Index scores are at increased risk for decline and incident NCI. The VACS Index shows promise as a tool for identifying HIV-infected persons at risk for NCI.

Authors
María J Marquine, Jessica L Montoya, Anya Umlauf, Pariya L Fazeli, Ben Gouaux, Robert K Heaton, Ronald J Ellis, Scott L Letendre, Igor Grant, David J Moore

Aidsmap material
Clinical Infectious Diseases abstract
VACS information


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