Search

OBJECTIVE: To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration following treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. SETTING: Single-arm, 24-week, open-label clinical trial. METHODS: HIV-infected individuals on antiretroviral therapy (ART) ≥1 year with plasma HIV RNA ≤50 copies/ml and below-normal cognitive performance [defined as age, gender and education-adjusted NP performance (NPZ)

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

OBJECTIVE: The antiretroviral drug efavirenz (EFV) has been linked to disordered sleep and cognitive abnormalities. We examined sleep and cognitive function and subsequent changes following switch to an alternative integrase inhibitor-based regimen. METHODS: Thirty-two HIV-infected individuals on EFV, emtricitabine, and tenofovir (EFV/FTC/TDF) without traditional risk factors for obstructive sleep apnea (OSA) were randomized 2:1 to switch to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) or to continue EFV/FTC/TDF therapy for 12 weeks. Overnight polysomnography and standardized sleep and neuropsychological assessments were performed at baseline and at 12 weeks. RESULTS: No significant differences in change over 12 weeks were noted between the two arms in any sleep or neuropsychological test parameter. At entry, however, the rate of sleep disordered breathing (SDB) was substantially higher in study subjects compared to published age-matched norms and resulted in a high assessed OSA rate of 59.4%. Respiratory Disturbance Index (RDI), a measure of SDB, correlated with age- and education-adjusted global neuropsychological z-score (NPZ) (r=-0.35, p=0.05). Sleep Maintenance Efficiency, Wake after Sleep Onset, REM Sleep and RDI correlated with domain-specific NPZ for learning and memory (all p-values ≤ 0.05). CONCLUSION: Among HIV-infected individuals on EFV-based therapy and without traditional risk factors for OSA, sleep and neuropsychological abnormalities do not readily reverse after discontinuation of EFV. High baseline rates of SDB and abnormalities in sleep architecture exist in this population correlating with neuropsychological impairment. The role of HIV immuno-virologic or lifestyle factors as contributing etiologies should be explored. OSA may be an under-recognized etiology for cognitive dysfunction during chronic HIV.

Few studies have examined systemic mitochondrial function in conjunction with brain imaging in human immunodeficiency virus (HIV) disease. Oxidative phosphorylation enzyme protein levels of peripheral blood mononuclear cells were measured in association with neuroimaging indices in 28 HIV+ individuals. T1-weighted magnetic resonance imaging yielded volumes of seven brain regions of interest; diffusion tensor imaging determined fractional anisotropy (FA) and mean diffusivity (MD) in the corpus callosum (CC). Higher nicotinamide adenine dinucleotide dehydrogenase levels correlated with lower volumes of thalamus (p = .005) and cerebral white matter (p = .049) and, in the CC, with lower FA (p = .011, body; p = .005, genu; p = .009, total CC) and higher MD (p = .023, body; p = .035, genu; p = .019, splenium; p = .014, total CC). Greater cytochrome c oxidase levels correlated with lower thalamic (p = .034) and cerebellar gray matter (p = .021) volumes. The results indicate that systemic mitochondrial cellular bioenergetics are associated with brain health in HIV.