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HIV-Associated Neurological Disorders

Overview of attention for article published in CNS Drugs, August 2012
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Title
HIV-Associated Neurological Disorders
Published in
CNS Drugs, August 2012
DOI 10.2165/11597770-000000000-00000
Pubmed ID
Authors

Ik L. Tan, Justin C. McArthur

Abstract

In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorder (HAND) continues to be a common and significant morbidity among individuals infected with HIV. The term HAND encompasses a spectrum of progressively severe CNS involvement, ranging from asymptomatic neurocognitive impairment and minor neurocognitive disorder through to the most severe form of HIV-associated dementia (HAD). While the incidence of HAD has declined significantly with HAART, the milder forms of HAND persist. In addition, HAND now develops in individuals with less advanced immunosuppression. The reasons for the persistence of milder forms of HAND in individuals treated with HAART are not entirely known. There are several hypotheses to explain this phenomenon that include the legacy effect, a failure of antiretroviral agents to reverse neurological damage, poor access of antiretroviral agents to the CNS, chronic systemic immune activation associated with microbial translocation products, sustained CNS inflammation, the improved survival of HIV-seropositive individuals and the possible contribution from aging, amyloid deposition and other co-morbidities. In contrast, the incidence of HIV-associated CNS opportunistic processes including progressive multifocal leukoencephalopathy, tuberculosis, CNS toxoplasmosis, cytomegalovirus encephalitis, cryptococcosis and primary CNS lymphoma has declined dramatically with the introduction of HAART. This review briefly summarizes our current understanding of HAND and the pathological mechanisms involved, namely direct injury from HIV-1 and viral proteins, indirect neurotoxicity from proinflammatory cytokines and chronic, sustained immune activation in the CNS. To date, only HAART has been shown to benefit HAND despite numerous controlled trials of adjunctive 'anti-inflammatory' agents. Although HAART has a profound impact on the incidence and severity of HAND, there exists a 'therapeutic gap' as even HAART that is effective at inducing durable virological suppression may only partially reverse HAND. In addition, there may be potential CNS adverse effects of antiretroviral agents. There is an ongoing multicentre clinical trial to investigate the role of the CNS Penetration-Effectiveness index, an indicator of drug permeability and availability in the CNS, to help guide the choice of antiretroviral agents in the treatment of HAND. With recent recommendations for earlier treatment intervention with HAART for HIV-1 infection, it remains to be seen the effects of this on HAND. There is an urgent need to better define the therapeutic guidelines for the prevention and treatment of HAND.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 109 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 2 2%
Netherlands 1 <1%
South Africa 1 <1%
United Kingdom 1 <1%
Spain 1 <1%
Unknown 103 94%

Demographic breakdown

Readers by professional status Count As %
Student > Master 21 19%
Researcher 16 15%
Student > Doctoral Student 13 12%
Student > Ph. D. Student 13 12%
Student > Postgraduate 8 7%
Other 17 16%
Unknown 21 19%
Readers by discipline Count As %
Medicine and Dentistry 46 42%
Agricultural and Biological Sciences 7 6%
Neuroscience 6 6%
Immunology and Microbiology 5 5%
Psychology 4 4%
Other 16 15%
Unknown 25 23%