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Background Combination antiretroviral therapy (cART) has transformed HIV into a manageable but complex chronic disease, in which it is uncertain which brain insults may relate to age vs initial disease severity. We evaluate N-acetyl-aspartate/creatine (NAA/Cr), white matter hyperintensities (WMH), and mean cortical thickness to identify which subclinical markers of brain insult best relate to CD4 nadir and aging. This is a prospective study of the association between brain markers with age and initial infection severity, based on CD4 nadir, in chronic HIV patients. Methods Thirty-seven chronic HIV patients (age 25–77 years) with successful viral suppression were scanned on a GE 3T magnetic resonance imaging scanner to obtain NAA/Cr (standardized and averaged over 5 brain regions), log-transformed WMH volume, and mean cortical thickness. The brain measures were fitted with both CD4 nadir and age to evaluate the significance of their relationship. Results NAA/Cr, WMH, and cortical thickness were all correlated with age and CD4 nadir in unadjusted associations. Stepwise regression models showed that NAA/Cr alone best predicted CD4 nadir (β = 40.1 ± 13.3; P = .005), whereas WMH (β = 2.3 ± .9; P = .02) and mean cortical thickness (β = –2.7 ± 6.6; P &amp;lt; .0001) together produced the best model fit with age. NAA/Cr was higher for HIV stage 1 (CD4 nadir ≥ 500 cells/ µL; n = 15) compared with stage 2 (200 ≥ CD4 nadir &amp;lt; 500; n = 13) and stage 3 (CD4 nadir &amp;lt; 200; n = 9; P &amp;lt; .01 for both). Conclusions In patients with effectively suppressed HIV, NAA reflects the subclinical brain impact of initial disease severity related to development of even mild immune compromise, whereas cortical thickness and WMH volume are useful to evaluate age-related changes.

Distinguishing Brain Impact of Aging and HIV Severity in Chronic HIV Using Multiparametric MR Imaging and MR Spectroscopy