HIV-associated neurological disorders: A guide to pharmacotherapy

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)123-134
Number of pages12
JournalCNS Drugs
Volume26
Issue number2
DOIs
StatePublished - 2012

Fingerprint

Nervous System Diseases
HIV-1
HIV
Drug Therapy
Highly Active Antiretroviral Therapy
Anti-Retroviral Agents
AIDS Dementia Complex
Neurocognitive Disorders
Incidence
Progressive Multifocal Leukoencephalopathy
Human Immunodeficiency Virus Proteins
Morbidity
Therapeutics
Cryptococcosis
Toxoplasmosis
Viral Proteins
Encephalitis
Cytomegalovirus
Amyloid
Immunosuppression

Keywords

  • Antiretrovirals
  • CNS-infections
  • Cognition-disorders
  • Dementia
  • HIV-1-infections
  • Immunocompromised-infections
  • Neuroprotectants
  • Neuurological-disorders
  • Progressive-multifocal-leukoencephalopathy

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Clinical Neurology

Cite this

HIV-associated neurological disorders : A guide to pharmacotherapy. / Tan, Ik L.; McArthur, Justin Charles.

In: CNS Drugs, Vol. 26, No. 2, 2012, p. 123-134.

Research output: Contribution to journalArticle

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