The Presence of Human Immunodeficiency Virus-Associated Neurocognitive Disorders Is Associated With a Lower Adherence to Combined Antiretroviral Treatment.

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are defined according to their diagnostic degrees as follows: asymptomatic neurocognitive impairment, mild neurocognitive disorder, and HIV-associated dementia. Because high adherence to combined antiretroviral therapy (cART) is required to maintain viral suppression among HIV-infected patients, it is important to investigate the impact of HAND on medication adherence. Our study hypothesis was that patients with HAND had a lower medication adherence than patients who did not have HAND. This was an observational, exploratory, 2-center pilot study of patients who had a state-of-the-art neurocognitive assessment performed between January 2011 and June 2015 while also being followed at their respective adherence clinics. Adherence was measured with electronic monitors. Patients' sociodemographic characteristics, HIV viral load, and CD4 counts were retrieved from the Swiss HIV Cohort Study database. At each time t, adherence was computed as the proportion of patients taking medication as prescribed at that time. We included 59 patients, with a median (Q1, Q3) age of 53 years (47-58) and 39 (66%) were male participants. Twenty-two patients (35%) had no neurocognitive deficits, 16 (27%) patients had HAND, and 21 (35%) patients had non-HAND (mostly depression). Implementation over 3 years showed a significant decline (50%) in medication adherence among patients diagnosed with HAND in comparison with patients who had a normal neuropsychological status or a non-HIV-related cognitive deficit (implementation stayed 90% during follow-up). Our findings support the hypothesis that HAND is associated with reduced cART adherence

Micro-Structural Brain Alterations in Aviremic HIV+ Patients with Minor Neurocognitive Disorders: A Multi-Contrast Study at High Field.

OBJECTIVE: Mild neurocognitive disorders (MND) affect a subset of HIV+ patients under effective combination antiretroviral therapy (cART). In this study, we used an innovative multi-contrast magnetic resonance imaging (MRI) approach at high-field to assess the presence of micro-structural brain alterations in MND+ patients. METHODS: We enrolled 17 MND+ and 19 MND- patients with undetectable HIV-1 RNA and 19 healthy controls (HC). MRI acquisitions at 3T included: MP2RAGE for T1 relaxation times, Magnetization Transfer (MT), T2* and Susceptibility Weighted Imaging (SWI) to probe micro-structural integrity and iron deposition in the brain. Statistical analysis used permutation-based tests and correction for family-wise error rate. Multiple regression analysis was performed between MRI data and (i) neuropsychological results (ii) HIV infection characteristics. A linear discriminant analysis (LDA) based on MRI data was performed between MND+ and MND- patients and cross-validated with a leave-one-out test. RESULTS: Our data revealed loss of structural integrity and micro-oedema in MND+ compared to HC in the global white and cortical gray matter, as well as in the thalamus and basal ganglia. Multiple regression analysis showed a significant influence of sub-cortical nuclei alterations on the executive index of MND+ patients (p = 0.04 he and R(2) = 95.2). The LDA distinguished MND+ and MND- patients with a classification quality of 73% after cross-validation. CONCLUSION: Our study shows micro-structural brain tissue alterations in MND+ patients under effective therapy and suggests that multi-contrast MRI at high field is a powerful approach to discriminate between HIV+ patients on cART with and without mild neurocognitive deficits

Boxplots representing data from the univariate analysis for WM, cGM, thalamus and basal ganglia.

<p>In each box, the central mark represents the median, the edges represent the 25th and 75th percentiles and the whiskers extend to the most extreme data points not considered outliers; outliers are plotted individually as x. HC: green; MND−: red; MND+: blue.</p

Demographics, HIV characteristics and neuropsychological results (raw scores and indexes) of MND+ and MND− patients.

<p>Demographics, HIV characteristics and neuropsychological results (raw scores and indexes) of MND+ and MND− patients.</p

Graphs showing the respective significance in each ROI for univariate analysis (loop), bivariate analysis (straight line) and multivariate analysis (central circle).

<p>Red color indicates p≤0.01 and yellow color indicates p≤0.05. Hypothesis 3.</p

Neuropsychological tests. References are reported in Data

<p>Neuropsychological tests. References are reported in Data</p

Quantitative/semi-quantitative maps and segmentation in regions of interest.

<p>Color coded T1 (A), MTR (B) and T2* (C) maps showing the distribution of the contrasts in an axial slide; In (D), region of interest segmentation of global gray matter (brown), white matter (green), thalamus (pink), caudate (blue), putamen (cyan) and globus pallidus (yellow) in one MND+ subject.</p

Graphs showing the respective significance in each ROI for univariate analysis (loop), bivariate analysis (straight line) and multivariate analysis (central circle).

<p>Red color indicates p≤0.01 and yellow color indicates p≤0.05. A) hypothesis 1, B) hypothesis 2.</p

Boxplots representing data from the univariate analysis for lobar WM and cGM.

<p>In each box, the central mark represents the median, the edges represent the 25th and 75th percentiles and the whiskers extend to the most extreme data points not considered outliers; outliers are plotted individually as x. HC: green; MND−: red; MND+: blue. FWM: frontal WM; PWM: parietal WM; TWM: temporal WM; OWM: occipital WM; FcGM: frontal cGM; PcGM: parietal cGM; TcGM: temporal cGM; OcGM: occipital cGM.</p