Members of the CHARTER Study Group are listed in the Appendix on page xx.
Article first published online: 9 DEC 2008
Copyright © 2008 American Neurological Association
Annals of Neurology
Volume 64, Issue 5, pages 566–572, November 2008
How to Cite
Ellis, R. J., Marquie-Beck, J., Delaney, P., Alexander, T., Clifford, D. B., McArthur, J. C., Simpson, D. M., Ake, C., Collier, A. C., Gelman, B. B., McCutchan, J. A., Morgello, S. and Grant, I. (2008), Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy. Ann Neurol., 64: 566–572. doi: 10.1002/ana.21484
Potential conflict of interest: Nothing to report.
- Issue published online: 9 DEC 2008
- Article first published online: 9 DEC 2008
- Manuscript Accepted: 11 JUL 2008
- Manuscript Revised: 18 JUN 2008
- Manuscript Received: 9 NOV 2007
- CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER)
- NIH. Grant Number: N01 MH22005
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.
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.
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.
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. Ann Neurol 2008;64:566–572