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HIV-1 infection and cognitive impairment in the cART era: a review. AIDS

aDepartment of Neurology, The Netherlands bInternal Medicine, Division of Infectious Diseases, Tropical Medicine & Aids, Academic Medical Center, Amsterdam, The Netherlands cCenter for Poverty-related Communicable Diseases, Academic Medical Center and Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands dDepartment of Neurology, OLVG Hospital, Amsterdam, The Netherlands eDepartment of Infectious Diseases, San Rafaele Scientific Institute, Milan, Italy fDepartment of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
AIDS (London, England) (Impact Factor: 6.56). 12/2010; 25(5):561-75. DOI: 10.1097/QAD.0b013e3283437f9a
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ABSTRACT With the introduction of combination antiretroviral therapy AIDS dementia complex or HIV-associated dementia, as it was termed later, largely disappeared in clinical practice. However, in the past few years, patients, long-term infected and treated, including those with systemically well controlled infection, started to complain about milder memory problems and slowness, difficulties in concentration, planning, and multitasking. Neuropsychological studies have confirmed that cognitive impairment occurs in a substantial (15-50%) proportion of patients. Among HIV-1-infected patients cognitive impairment was and is one of the most feared complications of HIV-1 infection. In addition, neurocognitive impairment may affect adherence to treatment and ultimately result in increased morbidity for systemic disease. So what may be going on in the CNS after so many years of apparently controlled HIV-1 infection is an urgent and important challenge in the field of HIV medicine. In this review we summarize the key currently available data. We describe the clinical neurological and neuropsychological findings, the preferred diagnostic approach with new imaging techniques and cerebrospinal fluid analysis. We try to integrate data on pathogenesis and finally discuss possible therapeutic interventions.

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Available from: Paola Cinque, Nov 23, 2014
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    • "As of 2012, the Word Health Organization estimates that approximately 35 million people are living with human immunodeficiency virus (HIV). Out of these, 30–60 % are expected to develop some form of HIV-associated neurocognitive disorder (HAND) despite treatment with antiretroviral therapy (cART) (Schouten et al. 2011). Novel biomarkers detectable in human biological fluids, such as blood, plasma, saliva, or cerebral spinal fluid (CSF), are needed to support earlier clinical diagnosis of HAND (reviewed in (Price et al. 2013)). "
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    ABSTRACT: We identified and measured proteins in the cerebral spinal fluid (CSF) involved in HIV-associated neurological disorders. Protein levels were determined by mass spectrometry (MS) in pooled CSF taken from three patient groups (human immunodeficiency virus (HIV)-1-infected patients that developed HIV-associated neurocognitive disorders (HANDs), HIV-1-infected patients without HAND, and healthy controls). Pools were generated from 10 patients each per group. CSF from individual patient groups were digested with trypsin and separately labeled using with isobaric tags for relative and absolute quantitation (iTRAQ). After combining all samples in one, peptides were extensively fractionated by offline two-dimensional separation and identified by tandem MS. One hundred and ninety three proteins were deemed to be interpretable for quantitation based on permutation tests with a 95 % confidence interval with a p value ≤ 0.05. Using a cutoff of 1.5-fold for upregulation and 0.6 for downregulation, 16 proteins were differentially expressed in HIV + HAND (reporter p value ≤0.05) with seven of them previously described as HIV-interacting proteins: endoplasmin, mitochondrial damage mediator-BH3-interacting domanin death agonist, orosomucoid, apolipoprotein E, metalloproteinase inhibitor 2, peroxiredoxin-2, and the nuclear protein, ruvB-like 2. Several previously unidentified proteins with possible neurological implication in HIV patients include forming-binding protein 1, C-reactive protein, leukocyte-associated immunoglobulin receptor 1, renin receptor, mediator of RNA polymerase II transcription subunit 14, multimerin-2, alpha-N-acetylglucosaminidase, caldesmon, and cadherin EGF LAG G-type receptor. Our results suggest that not only a few but possibly a combination of biomarkers that are highly correlated can predict neurocognitive status in HIV-infected patients and might be involved in monocyte or macrophage activation.
    Journal of NeuroVirology 07/2014; 20(5). DOI:10.1007/s13365-014-0263-5 · 3.32 Impact Factor
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    • "For instance, it might be the result of a process that has been going on for years, or it might be the exitus of a subacute deterioration in which viral control in the CNS is suddenly lost. As reported by Schouten et al. (2011), we still do not know whether such deterioration will strike each HIV-infected hemophiliac, or a subset of patients at risk. Such a review can give us insight into the literature and compare different results in different cohorts of patients, but at the same time, many aspects about the neurology system in these patients are an unknown. "
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    ABSTRACT: The debate regarding neurocognitive functions in the early stages of HIV infection is still ongoing; different studies have reached contrasting conclusions, probably because many of them take into account different cohorts of patients. A main distinction is between HIV seropositive patients infected perinatally, and those infected postnatally. The aim of this paper is to review results on neurocognitive dysfunctions and other types of neurological involvement in a specific cohort of HIV+ patients infected postnatally: hemophilia patients. Such a review is relevant, as HIV seropositive patients infected postnatally are understudied with respect to patients infected perinatally, and as the results of the few studies aiming at comparing them are contrasting. Taken together, the 11 studies reviewed suggest the presence of both long-term neurocognitive dysfunctions and neurological alterations, such as the presence of atrophic changes and lesions in the white matter. The current review may offer new research insights into the neurocognitive dysfunctions in HIV-patients, and on the nature of such dysfunctions.
    Frontiers in Human Neuroscience 06/2014; 8. DOI:10.3389/fnhum.2014.00470 · 2.90 Impact Factor
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    • "Cognitive impairment occurs in a substantial (15–50%) proportion of HIV-infected patient on highly active antiretroviral therapy (HAART). [9] [10] [11] It has also been reported that about 40% of patients treated with lamivudine develop toxicities "
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    ABSTRACT: Introduction. Lamivudine is a nucleoside reverse transcriptase inhibitor antiretroviral agent used in the treatment of human immunodeficiency virus type 1 infection. This study was to investigate the effects of coadministration of neurovite and lamivudine on the histomorphology of the cerebellum of Wistar rats. Materials and Methods. Twenty Wistar rats were divided equally into four groups. Group A animals were the control treated with distilled water. Groups B, C, and D animals were treated, respectively, with therapeutic dose of lamivudine (4.28 mg/kg), a combination of lamivudine (4.28 mg/kg) and neurovite (7.05 mg/kg), and neurovite (7.05 mg/kg) alone, daily. The rats were sacrificed using chloroform inhalation, processed, and stained using H&E method. Results. There was severe cellular degeneration with dystrophic changes, vacuolization in the molecular and granular layers, and aggregation of swollen Purkinje cells in group B animals compared with group C animals which showed only slight cellular dystrophy and inflammation. The mean cellular population was significantly (P < 0.05) higher in the treatment groups compared with the control. Conclusion. There was amelioration of damage of the cerebellum in the animals treated with neurovite and lamivudine combination compared to animals treated with only lamivudine. Therefore, there is need to give neurovite to patients on lamivudine therapy.
    01/2014; VOL 2014 Article ID 258040(4 PAGES). DOI:10.115/2014/258040
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