The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study

Clinical Infectious Diseases MAJOR ARTICLE HIV/AIDS The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study Maria J. Marquine, 1 Jessica L. Montoya, 1 Anya Umlauf, 1 Pariya L. Fazeli, 4 Ben Gouaux, 1 Robert K. Heaton, 1 Ronald J. Ellis, 2 Scott L. Letendre, 3 Igor Grant, 1 and David J. Moore 1 ; for the HIV Neurobehavioral Research Program Group Departments of 1 Psychiatry, 2 Neurosciences, and 3 Medicine, University of California, San Diego; and 4 Psychology Department, University of Alabama, Birmingham Background. The Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immu- nodeficiency 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. Keywords. HIV; biomarkers; cognitive impairment. The advent of combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection and its effects on the central nervous system (CNS). HIV infec- tion is now a chronic disease with multiple interacting causes of morbidity [1]. Although neurocognitive impairment (NCI) re- mains common in some HIV cohorts (35%–50% prevalence), neurocognitive deficits now tend to be milder than in the pre- ART era [2, 3]. Identifying persons with milder NCI is more difficult than identifying frank dementia and tends to require comprehensive and costly assessments. Even the milder forms of NCI may be associated with problems with everyday func- tioning (eg, impaired driving and medication nonadherence) [4, 5]. This highlights the importance of identifying, assessing and intervening in HIV-infected persons at risk for impaired Received 15 January 2016; accepted 7 May 2016; published online 19 May 2016. Correspondence: M. J. Marquine, University of California San Diego, HIV Neurobehavioral Research Program, 220 Dickinson St, Ste B (8231), San Diego, CA 92103 (mmarquine@ucsd. edu). Clinical Infectious Diseases ® 2016;63(5):694–702 © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. DOI: 10.1093/cid/ciw328 CID 2016:63 (1 September) HIV/AIDS and/or worsening neurocognitive function. Ascertaining biomarkers of HIV-associated NCI is one promising approach to detecting those at risk for NCI, particularly if these biomarkers are obtained as part of routine clinical care. Clinical investigation of biomarkers is also relevant to improve under- standing of the biomedical mechanisms underlying NCI in the ART era. The Veterans Aging Cohort Study (VACS) Index was developed as a composite marker of disease severity among HIV-infected persons based on routine clinical blood tests. It integrates age, “tra- ditional” biomarkers of HIV disease (ie, plasma RNA and current CD4 + T-cell counts) and “nontraditional” biomarkers, including markers of renal and liver function, anemia, and hepatitis C virus (HCV) coinfection [6, 7]. The VACS Index has been consis- tently associated with increased risk of death in HIV-infected per- sons [6, 8, 9]. It has also been linked to poor health outcomes, including increased risk for hospitalizations and medical intensive care unit admissions [10, 11], fragility fractures [12], frailty [13, 14], and concurrent extremity strength [15]. Prior work by our group found the cross-sectional association of the VACS Index with NCI to be significant but small [16], and particularly weak among His- panics [17].