Peripheral neuropathy in HIV: prevalence and risk factors

Abstract

Objectives: To estimate neuropathic sign/symptom rates with initiation of combination antiretroviral therapy (cART) in HIV-infected ART-naive patients, and to investigate risk factors for: peripheral neuropathy and symptomatic peripheral neuropathy (SPN), recovery from peripheral neuropathy/SPN after neurotoxic ART (nART) discontinuation, and the absence of peripheral neuropathy/SPN while on nART.

Design: AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trial participants who initiated cART in randomized trials for ART-naive patients were annually screened for symptoms/signs of peripheral neuropathy. ART use and disease characteristics were collected longitudinally.

Methods: Peripheral neuropathy was defined as at least mild loss of vibration sensation in both great toes or absent/hypoactive ankle reflexes bilaterally. SPN was defined as peripheral neuropathy and bilateral symptoms. Generalized estimating equation logistic regression was used to estimate associations.

Results: Two thousand, one hundred and forty-one participants were followed from January 2000 to June 2007. Rates of peripheral neuropathy/SPN at 3 years were 32.1/8.6% despite 87.1% with HIV-1RNA 400 copies/ml or less and 70.3% with CD4 greater than 350 cells/μl. Associations with higher odds of peripheral neuropathy included older patient age and current nART use. Associations with higher odds of SPN included older patient age, nART use, and history of diabetes mellitus. Associations with lower odds of recovery after nART discontinuation included older patient age. Associations with higher odds of peripheral neuropathy while on nART included older patient age and current protease inhibitor use. Associations with higher odds of SPN while on nART included older patient age, history of diabetes, taller height, and protease inhibitor use.

Conclusion: Signs of peripheral neuropathy remain despite virologic/immunologic control but frequently occurs without symptoms. Aging is a risk factor for peripheral neuropathy/SPN.

Fig. 1. Longitudinal characterisitics of peripheral neuropathy and combination antiretroviral therapy initiation

(a) Peripheral neuropathy over time. (b) Neuropathic signs over time. (c) Neuropathic symptoms over time. (d) Antiretroviral therapy (ART) use over time. d4t, stavudine; ddc, zalcitabine; ddi, didanosine; nART, neurotoxic antiretroviral therapy.

Fig. 2. Estimates of association with peripheral neuropathy and symptomatic peripheral neuropathy

(a) Odds ratio estimates [95% confidence interval (CI)] for peripheral neuropathy (PN) and symptomatic PN (SPN). (b) Odds ratio estimates (95% CI) for PN and SPN after neurotoxic antiretroviral therapy (nART) discontinuation. (c) Odds ratio estimates (95% CI) for PN and SPN while on nART. d4t, stavudine; ddc, zalcitabine; ddi, didanosine; ge, greater than or equal to; HCV, hepatitis C virus; IV, intravenous; le, less than or equal to; R, reference group. *Statistically significant (α ≤ 0.05).