Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy

Ronald J. Ellis, Jennifer Marquie-Beck, Patrick Delaney, Terry Alexander, David B. Clifford, Justin C. McArthur, David M. Simpson, Christopher Ake, Ann C. Collier, Benjamin B. Gelman, J. Allen McCutchan, Susan Morgello, Igor Grant, Thomas D. Marcotte, Donald Franklin, Scott Letendre, Edmund Capparelli, Janis Durelle, Robert K. Heaton, J. Hampton AtkinsonSteven Paul Woods, Matthew Dawson, Joseph K. Wong, Terry Jernigan, Michael J. Taylor, Rebecca Theilmann, Anthony C. Gamst, Clint Cushman, Ian Abramson, Florin Vaida, Rodney Von Jaeger, Justin McArthur, Gilbert Mbeo, David Simpson, Letty Mintz, Susan Ueland, Ann Collier, Christina Marra, Trudy Jones, Benjamin Gelman, Eleanor Heckendorn, Muhammad Al-Lozi, Mengesha Teshome

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Objective: Two recent analyses found that exposure to protease inhibitors (PIs) in the context of antiretroviral (ARV) therapy increased the risk for distal sensory polyneuropathy (DSPN) in subjects with human immunodeficiency virus (HIV) infection. These findings were supported by an in vitro model in which PI exposure produced neurite retraction and process loss in dorsal root ganglion sensory neurons. Confirmation of peripheral nerve toxicity with PIs could substantially limit their long-term use in highly active ARV therapy. Methods: We evaluated current and past exposure to PIs as a risk factor for DSPN in 1,159 HIV-infected individuals enrolled in a large, prospective, observational, multicenter study. Signs of DSPN were ascertained by neurological examination. Subjects were grouped into categories according to past and current exposure to any ARV and to PIs. We included disease indicators such as nadir CD4, plasma viral load, and duration of HIV infection, as well as advancing age and exposure to dideoxynucleoside ARVs in multivariate models. Results: In univariate analyses, both past and current PI exposure significantly increased the risk for DSPN. However, after adjusting for previously validated concomitant risk factors in multivariate models, none of the PI exposure groups was more likely to have DSPN than ARV naive subjects. A secondary evaluation of duration of PI use and exposure to individual PI drugs was similarly nonsignificant in multivariate models, except for small effects of amprenavir and lopinavir. Interpretation: Evaluation of concomitant risks for HIV DSPN suggests that the independent risk attributable to PIs, if any, is small. This risk must be weighed against the important role of PIs in modern ARV therapy regimens.

Original languageEnglish (US)
Pages (from-to)566-572
Number of pages7
JournalAnnals of Neurology
Issue number5
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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