The finding: This study utilized data from 655 HIV-infected participants in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program to examine the association between the Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity, and neurocognitive impairment (NCI) incidence and change, over a follow-up period of up to 6 years. Significant findings were as follows: 1) There was no significant association between baseline VACS Index scores and change in global neurocognitive functioning. 2) However, changes in VACS Index scores were associated with an increased risk of developing neurocognitive impairment in a subgroup of participants without neurocognitive impairment at baseline. 3) When participants were categorized by quartiles, those with the highest VACS Index scores (upper quartile) were at significantly higher risk for neurocognitive decline; participants in the upper quartile having no neurocognitive impairment at baseline were twice as likely to develop incident NCI compared to those in the low VACS Index group.

Strengths and weaknesses: This study uses a prospective design, large number of subjects, a well-researched marker of HIV disease severity that is based on routine clinical blood tests, the VACS Index score, and a comprehensive neurocognitive battery that has been validated in individuals with HIV, to explore the association between easily obtained biomarkers and NCI. The participants were largely white, male, and young, thus findings may not generalize to other ethnic/racial groups and women. This study also is less relevant to the growing population of older HIV-infected individuals who present other non-HIV related causes of cognitive decline. Additionally, because many participants were diagnosed before effective treatment was available, more recently infected individuals may present different findings.

Relevance: Advances in HIV treatment have been accompanied by a dramatic fall in the incidence of HIV-associated dementia while the prevalence of more attenuated forms of HIV-associated neurocognitive disorders (HAND) may be rising. Despite milder clinical symptoms, less severe HAND may be associated with medication nonadherence, limitations in daily functioning, increased morbidity and mortality and progression of neurocognitive impairment. Identification of milder HAND typically requires time-consuming and costly neuropsychological assessments. Therefore there is a need to improve ease and accuracy of diagnosing HAND. Such advances will enable more accurate identification of individuals for whom comprehensive neuropsychological evaluation will be of value and facilitate development of strategies for mitigating risk of progression of cognitive impairment.