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Neurobiology of Multiple Insults: HIV-1-Associated Brain Disorders in Those Who Use Illicit Drugs

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Abstract

Despite two decades of research, certain aspects of HIV-related central nervous system (CNS) disease remain poorly understood. HIV targets microglia and macrophages within the CNS and enters the brain compartment early. However, HIV is there held in check apparently until the onset of significant immune compromise, when viral replication, microglial activation, neuronal damage, and cognitive impairment are likely to ensue. Illicit drug abuse continues to be a significant risk factor for HIV transmission worldwide. Whether HIV-related CNS disease is more prevalent or more severe in this risk group has long been debated. Drugs of abuse can of themselves cause immune suppression, blood–brain barrier breakdown, microglial activation, and neuronal injury. This review presents evidence that HIV associated CNS disorders are indeed accentuated in drug abusers. However, the advent of effective therapy has added a new dimension, which must be taken into consideration. Treated individuals are surviving much longer and HIV encephalitis and HIV-associated dementia have become much less common. However, more subtle forms of CNS damage are emerging. Examination of the brains of individuals who have been treated long term with highly active antiretroviral therapy (HAART) reveals a surprising degree of microglial activation, comparable at times to that seen formerly in milder cases of HIV encephalitis. In addition, these individuals show evidence of increased deposition of neurodegenerative proteins, particularly hyperphosphorylated tau. Similar observations have been made in young opiate abusers who are HIV negative. Taken together, these results suggest that neuroinflammation and neurodegeneration, which are clinically silent at present, may cause problems in the future in HAART-treated subjects.

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Acknowledgements

The authors would like to pay tribute to the patients and their families for their help without which our HIV-related studies during the last 15 years would not have been possible. Among the many clinical collaborators and research scientists whom we would warmly acknowledge are Professor Peter Simmonds, Mr. Steve Ramage and Mrs. Frances Carnie. Funding support from the UK Medical Research Council, from the US National Institute on Drug Abuse, and from the European Community is gratefully acknowledged. We thank Ms Angela Penman for preparing the manuscript.

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  1. Neuropathology Division & Forensic Medicine Unit, University of Edinburgh, Scotland, EH8 9AG, UK

    Jeanne E. Bell, Juan-Carlos Arango & Iain C. Anthony

  2. Pathology (Neuropathology), Alexander Donald Building, Western General Hospital, Edinburgh, EH4 2XU, UK

    Jeanne E. Bell

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Correspondence to Jeanne E. Bell.

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Bell, J.E., Arango, JC. & Anthony, I.C. Neurobiology of Multiple Insults: HIV-1-Associated Brain Disorders in Those Who Use Illicit Drugs. Jrnl NeuroImmune Pharm 1, 182–191 (2006). https://doi.org/10.1007/s11481-006-9018-2

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