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

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
Source: PubMed

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.


Available from: Paola Cinque, Nov 23, 2014
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite successful combined antiretroviral therapy, ∼60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction. Copyright © 2015 by The American Association of Immunologists, Inc.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Apathy remains a common neuropsychiatric disturbance in the Human Immunodeficiency Virus (HIV-1) despite advances in anti-retroviral treatment (ART). The goal of the current review is to recapitulate findings relating apathy to the deleterious biobehavioral effects of HIV-1 in the post-ART era. Available literatures demonstrate that the emergence of apathy with other neurocognitive and neuropsychiatric symptoms may be attributed to neurotoxic effects of viral proliferation, e.g., aggregative effect of Tat and gp120 on apoptosis, transport and other enzymatic reactions amongst dopaminergic neurons and neuroglia. An assortment of neuroimaging modalities converge on the severity of apathy symptoms associated with the propensity of the virus to replicate within frontal-striatal brain circuits that facilitate emotional processing. Burgeoning research into functional brain connectivity also supports the effects of microvascular and neuro-inflammatory injury linked to aging with HIV-1 on the presentation of neuropsychiatric symptoms. Summarizing these findings, we review domains of HIV-associated neurocognitive and neuropsychiatric impairment linked to apathy in HIV. Taken together, these lines of research suggest that loss of affective, cognitive and behavioral inertia is commensurate with the neuropathology of HIV-1. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience & Biobehavioral Reviews 05/2015; DOI:10.1016/j.neubiorev.2015.04.008 · 10.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. Methods: The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients’ awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. Results: Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. Conclusions: These findings suggest that cocaine users enter into treatment with a range of NCI – with women having significantly more neurocognitive deficits than men – that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients.
    Substance Abuse: Research and Treatment 03/2015; 9:17-24. DOI:10.4137/SART.S23332