Disfunção cognitiva e HIV identificação de biomarcadores para o diagnóstico precoce

After combined antiretroviral therapy (cART) implementation there was a significant improvement on HIV infected patient’s survival, which increased the prevalence of chronic degenerative diseases, including neurocognitive diseases. The neurological manifestations, called HANDs (HIV-associated neurcognitive disorders), interfere with work capacity, and survival of HIV infected patients. The mechanisms involved on HANDs development are not well established, and a better understanding can impact directly on clinical management, diagnosis and treatment of those patients. Our objective was to evaluate the relationship between cognitive dysfunction, systemic inflammatory response and brain morphological and metabolic changes in a population of asymptomatic HIV-infected patients, without prior exposure to cART. We did a cross-sectional observational study, in which we selected HIV-infected patients in attendance at the National Institute of Infectious Diseases Evandro Chagas (INI/FIOCRUZ). After neurocognitive evaluation patients classified as normal (N), or as having some cognitive impairment: asymptomatic neurocognitive impairment (ANI); mild neurocognitive disorder (MND) and HIV associated dementia (HAD). We collected plasma samples to evaluate 37 biomarkers (inflammatory and neurodegenerative). The patients underwent MRI to morphological, spectroscopy and tractography evaluation. We included 52 patients, median age of 33 years (IQR, 25-75: 28 to 43.75), with a predominantly male (65%), with 578 median CD4+ counts (IQR, 25-75: 432-743). Among the patients included 31 (59.5%) presented normal cognitive performance (N), 15 (29%) MND or ANI, and 6 (11.5%) HAD, which is a 40,5% of HANDs prevalence. Among 37 biomarkers evaluated we analyzed 12 of them, those that were detectable above 75% of sample tested. Comparing 12 biomarkers in plasma (HIV vs non-HIV), we observed levels statistically higher (p <0.05) in HIV patients in 9 of them: PDGF-BB, IP-10, BDNF, Cathepsin D, PAI-1, PDGF-AA, PDGF-AB / BB, RANTES, sICAM-1. We observe no significant difference in biomarkers levels amog patients stratified by cognitive evaluation (N + vs ANI+MND vs HAD) Cerebral parenchyma evaluated by magnetic ressonace (structural neuroimaging) we did not observed alteration that coud explain the occurrence of HANDs. Analyzing spectroscopy we observed an increase in the ratio MI/NAA (myo-inositol / N-acetyl-aspartate), in posterior parietal lobe in patients classified as HAD. Analyzing tractography data we observed white matter connectivity integrity altered in patients with HAD, in the corpus callosum (CC), in corona radiata of the anterior thalamus (left and right) in costicoespinhal tract (left and right), major and minor forceps, fronto-occipital (left and right), and the uncinate fasciculus (left and right) (p <0.05). Among asymptomatic HIV-infected patients, we observe cognitive changes under diagnosed in 40.5% of our sample. Among the main mechanisms involved in the pathophysiology of HANDs, toxicity by the virus itself seems to be the earliest and most important, which seems to be related to white matter connectivity changes in the brain of patients with HANDs.