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Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era.

ABSTRACT: BACKGROUND:Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables. METHODS:Multiple novel neuroimaging techniques (deformation-based morphometry, voxel-based morphometry, and cortical modeling) were used to assess regional brain volumes in 125 HIV-infected patients and 62 HIV-uninfected individuals. Ninety percent of the HIV-infected patients were on stable HAART with most of them (75%) having plasma viral suppression. Brain volumetrics and cortical thickness estimates were compared between the HIV-infected and uninfected groups, and the relationships between these measures of brain volume and indices of current and past infection severity, central nervous system penetration of HAART, and cognitive performance were assessed. RESULTS:Regionally specific patterns of reduced thalamic and brainstem volumes and reduced cortical thickness in the orbitofrontal cortex, cingulate gyrus, primary motor and sensory cortex, temporal, and frontal lobes were seen in HIV-infected patients compared to HIV-uninfected participants. Observed white matter loss and subcortical atrophy were associated with lower nadir CD4 cell counts, while reduction in cortical thickness was related to worse cognitive performance. CONCLUSIONS:Our findings suggest that distinct mechanisms may underlie cortical and subcortical injury in people with HIV and argues for the potential importance of early initiation of HAART to protect long-term brain health.

SUBMITTER: Sanford R

PROVIDER: S-EPMC5340610 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era.

Sanford Ryan R Fernandez Cruz Ana Lucia AL Scott Susan C SC Mayo Nancy E NE Fellows Lesley K LK Ances Beau M BM Collins D Louis DL

Journal of acquired immune deficiency syndromes (1999) 20170401 5

<h4>Background</h4>Cognitive impairment still occurs in a substantial subset of HIV-infected patients, despite effective viral suppression with highly active antiretroviral therapy (HAART). Structural brain changes may provide clues about the underlying pathophysiology. This study provides a detailed spatial characterization of the pattern and extent of brain volume changes associated with HIV and relates these brain measures to cognitive ability and clinical variables.<h4>Methods</h4>Multiple n ...[more]

PMID: 28129254

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Project description:Neurocognitive impairment remains prevalent in HIV-infected (HIV+) individuals despite highly active antiretroviral therapy (HAART). We assessed the impact of HIV, HAART, and aging using structural neuroimaging.Seventy-eight participants [HIV- (n = 26), HIV+ on stable HAART (HIV+/HAART+; n = 26), HIV+ naive to HAART (HIV+/HAART-; n = 26)] completed neuroimaging and neuropsychological testing. A subset of HIV+ subjects (n = 12) performed longitudinal assessments before and after initiating HAART. Neuropsychological tests evaluated memory, psychomotor speed, and executive function, and a composite neuropsychological score was calculated based on normalized performances (neuropsychological summary Z score, NPZ-4). Volumetrics were evaluated for the amygdala, caudate, thalamus, hippocampus, putamen, corpus callosum, and cerebral gray and white matter. A 3-group 1-way analysis of variance assessed differences in neuroimaging and neuropsychological indices. Correlations were examined between NPZ-4 and volumetrics. Exploratory testing using a broken-stick regression model evaluated self-reported duration of HIV infection on brain structure.HIV+ individuals had significant reductions in brain volumetrics within select subcortical regions (amygdala, caudate, and corpus callosum) compared with HIV- participants. However, HAART did not affect brain structure as regional volumes were similar for HIV+/HAART- and HIV+/HAART+. No association existed between NPZ-4 and volumetrics. HIV and aging were independently associated with volumetric reductions. Exploratory analyses suggest caudate atrophy due to HIV slowly occurs after self-reported seroconversion.HIV associated volumetric reductions within the amygdala, caudate, and corpus callosum occurs despite HAART. A gradual decline in caudate volume occurs after self-reported seroconversion. HIV and aging independently increase brain vulnerability. Additional longitudinal structural magnetic resonance imaging studies, especially within older HIV+ participants, are required.

Project description:Background:Cryptococcus neoformans is a frequent opportunistic infection in patients with the acquired immunode?ciency syndrome. While the advent of ART reduces the occurrence of cryptococcal meningitis in HIV patients, cryptococcal disease remains a leading cause of morbidity and mortality in the developing world especially in sub-Saharan Africa which is the epicenter of HIV. This study aimed to assess the cryptococcal antigenemia, CD4+ Th cell counts, HIV RNA viral load, and clinical presentations among HIV-positive patients in Northwest Ethiopia. Method:A total of two hundred (200) HIV-positive patients were recruited for this study. Cryptococcus antigenemia prevalence in plasma samples of HIV-positive patients was determined by using Antigen lateral ?ow assay (CrAg-LFA) also, and CD4+ Th cell counts and HIV-RNA levels were quantified from blood specimen. Patients' demographic data, clinical manifestation, and concurrent opportunistic infection were recorded. Result:The sex distributions of study participants were 105(52.5%) male and 94(47.5%) female with an age range of 15-65 (mean 39.42?±?9) years. All patients had a CD4+ T-cell count <100?cells/µl with the median 54?cells/?l and median HIV-RNA viral load 2.16?×?105 RNA copies/ml (50-3.66?×?105 RNA copies/ml); the prevalence of cryptococcal antigenemia was found to be 4% in HIV-positive patients. More than half and two third of CrAg-positive patients had a CD4 count <25?cells/?l and HIV viral load >10,000 copies/ml, respectively, as well; Tuberculosis, Candidiasis, and herpes zoster are the most often observed concurrent infections while cryptococcal antigenemia is significantly associated with oral candidiasis (p < 0.001). Conclusion:Although the advent of ART, early diagnosis of cryptococcosis, and application of antifungal interventions, HIV-induced cryptococcal antigenemia positivity in HIV infected individuals is still the countries' big challenge. Thus, stringent follow-up and case management should be considered.

Dataset Information

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era.

Publications

Regionally Specific Brain Volumetric and Cortical Thickness Changes in HIV-Infected Patients in the HAART Era.

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