Neurocognitive Dysfunction With Neuronal Injury in People With HIV on Long-Duration Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses. METHODS: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study. Brain MRI and lumbar puncture were optional. Coarsened Exact Matching was used to reduce between-group differences in age and sex, and weighted linear/logistic regression models were used to assess the effect of HIV on outcomes. RESULTS: Data were analyzed from 155 PWH on ART for at least 15 years and 100 HIV-negative controls. Compared with controls, PWH scored lower in the domains of attention/working memory (PWH least square mean [LSM] = 50.4 vs controls LSM = 53.1, p = 0.008) and motor function (44.6 vs 47.7, p = 0.009) and a test of information processing speed (symbol search 30.3 vs 32.2, p = 0.003). They were more likely to self-report a higher number of cognitive difficulties in everyday life (p = 0.011). PWH also reported more depressive symptoms, general anxiety, and use of psychiatric medications (all with p < 0.05). PWH had reduced proportions of subcortical gray matter on MRI (ß = -0.001, p < 0.001), and CSF showed elevated levels of neurofilament light chain (664 vs 529 pg/mL, p = 0.01) and tumor necrosis factor α (0.229 vs 0.156 ng/mL, p = 0.0008). DISCUSSION: PWH, despite effective ART for over a decade, displayed neurocognitive deficits and mood abnormalities. MRI and CSF analyses revealed reduced brain volume and signs of ongoing neuronal injury and neuroinflammation. As the already large proportion of virologically controlled PWH continues to grow, longitudinal studies should be conducted to elucidate the implications of cognitive, psychiatric, MRI, and CSF abnormalities in this group.

Retinal Thinning in People With Well-Controlled HIV Infection.

BACKGROUND: Retinal measurements correlate with disease progression in patients with multiple sclerosis; however, whether they associate with neurologic disease in people with controlled HIV is unknown. Using spectral domain optical coherence tomography, we evaluated retinal differences between people with HIV and HIV-negative controls and investigated clinical correlates of retinal thinning. METHODS: People with HIV on antiretroviral therapy for at least 1 year and HIV-negative controls recruited from the same communities underwent spectral domain optical coherence tomography, ophthalmic examination, brain MRI, and neuropsychological testing. Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GC-IPL) thicknesses were compared between groups using analysis of covariance with relevant clinical variables as covariates. Linear regression was used to explore associations of HIV history variables, cognitive domain scores, and MRI volume measurements within the HIV group. RESULTS: The HIV group (n = 69), with long-duration HIV infection (median time from diagnosis 19 years) and outstanding viral control have thinner retinal layers than HIV-negative controls (n = 28), after adjusting for covariates (GC-IPL: P = 0.002; RNFL: P = 0.024). The effect of HIV on GC-IPL thickness was stronger in women than in men (Women: P = 0.011; Men: P = 0.126). GC-IPL thickness is associated with information processing speed in the HIV group (P = 0.007, semipartial r = 0.309). No associations were found with retinal thinning and MRI volumes or HIV factors. CONCLUSIONS: People with HIV on antiretroviral therapy have thinning of the RNFL and GC-IPL of the retina, and women particularly are affected to a greater degree. This retinal thinning was associated with worse performance on tests of information processing speed.

Effect of HIV and Interpersonal Trauma on Cortical Thickness, Cognition, and Daily Functioning.

BACKGROUND: Interpersonal trauma (IPT) is highly prevalent among HIV-positive (HIV+) individuals, but its relationship with brain morphology and function is poorly understood. SETTING: This cross-sectional analysis evaluated the associations of IPT with cognitive task performance, daily functioning, magnetic resonance imaging (MRI) brain cortical thickness, and bilateral volumes of 4 selected basal ganglia regions in a US-based cohort of aviremic HIV+ individuals, with (HIV+ IPT+) and without IPT exposure (HIV+ IPT-), and sociodemographically matched HIV-negative controls with (HIV- IPT+) and without IPT exposure (HIV- IPT-). METHODS: Enrollees completed brain MRI scans, a semistructured psychiatric interview, a neurocognitive battery, and 3 measures of daily functioning. Demographic and clinical characteristics of the 4 groups were described, and pairwise between-group comparisons performed using χ tests, analysis of variance, or t-tests. Linear or Poisson regressions evaluated relationships between group status and the outcomes of interest, in 6 pairwise comparisons, using Bonferroni correction for statistical significance. RESULTS: Among 187 participants (mean age 50.0 years, 63% male, 64% non-white), 102 were HIV+ IPT+, 35 were HIV+ IPT-, 26 were HIV- IPT-, and 24 were HIV- IPT+. Compared with the remaining 3 groups, the HIV+ IPT+ group had more activities of daily living declines, higher number of impaired Patient's Assessment of Own Functioning Inventory scores, and lower cortical thickness in multiple cerebral regions. Attention/working memory test performances were significantly better in HIV- IPT- compared with the HIV+ IPT+ and HIV+ IPT- groups. Basal ganglia MRI volumes were not significantly different in any between-group comparisons. CONCLUSION: IPT exposure and HIV infection have a synergistic effect on daily functioning and cortical thickness in aviremic HIV+ individuals.

Global and regional brain hypometabolism on FDG-PET in treated HIV-infected individuals.

OBJECTIVE: To quantitatively measure brain glucose metabolism in treated HIV-positive individuals with [18F]-labeled fluorodeoxyglucose (FDG) PET/CT. METHODS: We performed a cross-sectional comparison of FDG uptake in 47 treated HIV+ individuals, 10 age-matched controls (HIV-) sharing many of the comorbid conditions seen in the HIV+ group, and 19 age-matched healthy controls (HCs). We compared whole-brain (WB) and regional FDG standardized uptake values (SUVs) of select subcortical/central structures among the groups and correlated the values to clinical and neuropsychological assessments. A variable selection model was used to predict SUVs in HIV+ (n = 47) and in combined HIV+ and HIV- participants (n = 57). RESULTS: We found lower WB SUVmax in HIV+ participants compared to HCs but not to HIV- participants. Among the relative SUVmean measurements (regional SUVmean/WB SUVmean), only relative thalamic uptake values were lower in HIV+ compared to HIV- participants. When HIV+ and HIV- participants were grouped, cardiovascular disease risk scores best predicted WB SUVmean and SUVmax, while HIV status best predicted thalamic relative SUVmean. CONCLUSIONS: We identified an important role for cardiovascular disease in neuronal loss/dysfunction, as measured by FDG-PET, in treated HIV+ patients. This underscores the need for shifting the focus of clinical intervention in this vulnerable population from HIV effects alone to a wider set of comorbid conditions, mainly cardiovascular disease. Only the thalamus showed significantly lower relative uptake in the HIV+ compared to the HC and HIV- groups. This needs to be further evaluated for underlying pathophysiology and potential association with memory, executive functioning, and attention deficits seen in the HIV+ population.