Human immunodeficiency virus protease inhibitors and risk for peripheral neuropathy

• Published in: Annals of neurology Vol. 64; no. 5; pp. 566 - 572
• Main Authors: Ellis, Ronald J., Marquie-Beck, Jennifer, Delaney, Patrick, Alexander, Terry, Clifford, David B., McArthur, Justin C., Simpson, David M., Ake, Christopher, Collier, Ann C., Gelman, Benjamin B., McCutchan, J. Allen, Morgello, Susan, Grant, Igor
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2008; Wiley-Liss
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Acquired Immunodeficiency Syndrome - enzymology; Acquired Immunodeficiency Syndrome - virology; Adult; Age Factors; Antiretroviral Therapy, Highly Active - adverse effects; Biological and medical sciences; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; HIV Protease Inhibitors - adverse effects; HIV-1 - drug effects; HIV-1 - enzymology; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neurology; Peripheral Nerves - drug effects; Peripheral Nerves - pathology; Peripheral Nerves - physiopathology; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - epidemiology; Prospective Studies; Risk Factors; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - pathology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virus; Nervous system diseases; Risk factor; Retroviridae; Peripheral nerve disease; Human immunodeficiency virus; Lentivirus; Protease inhibitor
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.21484

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. Ann Neurol 2008;64:566–572