title: Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of California, San Diego, San Diego, CA, USA. roellis@ucsd.edu
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marquie-Beck
authors.forename: Patrick
authors.initials: P
authors.lastname: Delaney
authors.forename: Terry
authors.initials: T
authors.lastname: Alexander
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Justin C
authors.initials: JC
authors.lastname: McArthur
authors.forename: David M
authors.initials: DM
authors.lastname: Simpson
authors.forename: Christopher
authors.initials: C
authors.lastname: Ake
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Gelman
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.forename: Susan
authors.initials: S
authors.lastname: Morgello
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000821:virology; D000328:Adult; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D003430:Cross-Sectional Studies; D005260:Female; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D011446:Prospective Studies; D012307:Risk Factors; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000473:pathology; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors