Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients

Protease inhibitor-mediated neurotoxicity

Jacqueline A. Pettersen, Gareth Jones, Catherine Worthington, Hartmut B. Krentz, Oliver T. Keppler, Ahmet Hoke, M. John Gill, Christopher Power

Research output: Contribution to journalArticle

Abstract

Objective: Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) is a common and disabling disorder, often associated with antiretroviral therapy (ART) use. We investigated the clinical features and associated pathogenic determinants of HIV-SN in a neurological cohort of HIV-infected patients, together with a novel model of HIV-SN. Methods: HIV-infected patients with neurological disease were investigated in terms of clinical and laboratory aspects together with ART exposure focusing on symptomatic HIV-SN. Rat-derived dorsal root ganglion (DRG) cultures, transgenic for human CD4 and CCR5 treated with ARTs or HIV infected, or both, were studied with respect to quantitative neuronal injury. Results: Among 221 patients assessed from 1998 to 2004, 120 had no sensory neuropathy, whereas 101 displayed HIV-SN, including 64 with distal sensory neuropathy and 37 with antiretroviral toxic neuropathy. HIV-SN patients exhibited significantly greater mean age, peak plasma viral loads, and exposure to neurotoxic dideoxynucleosides and protease inhibitors, including indinavir, saquinavir, or ritonavir. HIV-infected DRG cultures exposed to indinavir or didanosine showed significant neuronal atrophy, neurite retraction, and process loss, compared with controls. Indinavir was selectively cytotoxic to DRG macrophages compared with other ARTs. Interpretation: Protease inhibitor exposure is an unrecognized risk factor for the development of HIV-SN, which may potentiate neuronal damage in HIV-infected DRGs, possibly through the loss of macrophage-derived trophic factors.

Original languageEnglish (US)
Pages (from-to)816-824
Number of pages9
JournalAnnals of Neurology
Volume59
Issue number5
DOIs
StatePublished - May 2006

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Protease Inhibitors
Acquired Immunodeficiency Syndrome
HIV
Indinavir
Spinal Ganglia
Dideoxynucleosides
Macrophages
Implosive Therapy
Saquinavir
Didanosine
Ritonavir
Poisons
Diagnosis-Related Groups
Neurites
Viral Load
Atrophy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients : Protease inhibitor-mediated neurotoxicity. / Pettersen, Jacqueline A.; Jones, Gareth; Worthington, Catherine; Krentz, Hartmut B.; Keppler, Oliver T.; Hoke, Ahmet; Gill, M. John; Power, Christopher.

In: Annals of Neurology, Vol. 59, No. 5, 05.2006, p. 816-824.

Research output: Contribution to journalArticle

Pettersen, Jacqueline A. ; Jones, Gareth ; Worthington, Catherine ; Krentz, Hartmut B. ; Keppler, Oliver T. ; Hoke, Ahmet ; Gill, M. John ; Power, Christopher. / Sensory neuropathy in human immunodeficiency virus/acquired immunodeficiency syndrome patients : Protease inhibitor-mediated neurotoxicity. In: Annals of Neurology. 2006 ; Vol. 59, No. 5. pp. 816-824.
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