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Peripheral Neuropathy in ART-experienced Patients: Prevalence and Risk Factors
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
Huichao Chena, David B. Clifford*b, Lijuan Denga, Kunling Wua, Anthony J. Leea, Ronald J. Boscha, Ronald J. Ellisc, Scott R. Evansa
aHarvard School of Public Health, Boston, MA, USA; bWashington University, Saint Louis, MO, USA; cUniversity of California at San Diego, San Diego, CA, USA
ABSTRACT
Background: Peripheral neuropathy (PN) is the most common neurological complication of HIV infection. While there is some literature on the prevalence of neuropathic signs/symptoms and risk factors (RFs) for PN or symptomatic PN (SPN) with initiation of combination antiretroviral therapy (cART) in ART- na•ve patients, the research in ART-experienced patients is limited. This study aims to investigate the prevalence and RFs for PN/SPN in ART-experienced patients.
Methods: Between January 2000 and June 2007, signs and symptoms of PN were annually assessed by trained site personnel via a brief PN screen for ART-experienced patients from the ACTG A5001 cohort that started or continued cART in randomized trials. PN was defined as at least mild loss of vibration sensation in both great toes or absent or hypoactive ankle reflexes bilaterally relative to knees. SPN was defined as PN plus bilateral symptoms. Generalized estimating equation (GEE) logistic regression was used in the analysis.
Results: 1093 ART-experienced patients (88% male, 60% white, 20% black, median age=44 yrs, median log10 HIV-1 RNA=3.8, and median CD4=292 cells/μl at parent study entry) were analyzed.
PN/SPN persisted with improved immunologic function and virologic control. Associations with higher odds of PN included older patient age [OR=1.74 per 10yrs, 95%CI = (1.53, 1.97), p<0.001], taller height [OR=1.17 per 5cm, 95%CI = (1.09, 1.25), p<0.001], current protease inhibitor (PI) use [OR=1.25, 95%CI = (1.06, 1.48), p=0.009], and history of intravenous (IV) drug use [OR=1.47, 95%CI = (1.08, 1.99), p=0.014]. Notable factors associated with higher odds of SPN included older age [OR=1.75, 95%CI = (1.49, 2.04), P<0.001], taller height [OR=1.22, 95%CI = (1.11, 1.34), P<0.001], current PI use [OR=1.58, 95%CI = (1.26, 1.99), P<0.001], and history of IV drug use [OR=1.92, 95%CI = (1.37, 2.71), P<0.001].
Conclusions: Signs of PN remain despite virologic / immunologic control and the decline of nART use. Aging, taller height, PI use, and history of IV drug use are RFs for PN and SPN. Unlike ART-na•ve patients, nART use is not associated with PN/SPN.
BACKGROUND
Combination antiretroviral (cART) therapy has resulted in declines in the incidences of HIV-associated dementia and central nervous system (CNS) opportunistic infections. However sensory neuropathies (SNs) are still prevalent and the most frequent neurological disorder associated with HIV infection and its treatment with ART.
There are two major types of HIV-associated distal sensory peripheral neuropathies: primary HIV-associated distal sensory polyneuropathy (HIV-DSP) and ART toxic neuropathy (ATN), together which affect approximately 30%-67% of patients with advanced HIV disease. HIV- DSP is the most common SN in HIV infection with a reported one-year incidence in an advanced-patient cohort selected for neurologic disease risk of 36%/21% in the pre-cART/cART eras respectively. ATN is the most common toxicity of ART therapy in Sub-Saharan Africa.
The symptoms of HIV-DSP and ATN include numbness, paresthesia, burning sensation, and stabbing pain. Common signs include reduced or absent ankle reflexes relative to patellar reflexes, reduced or absent vibration sensation in the toes, and decreased pin and temperature sensation in a stocking/glove distribution.
No FDA-approved therapies exist for HIV-associated SNs with treatment limited to symptomatic measures with limited efficacy.
Higher plasma HIV-1 RNA and lower CD4+ cell counts before the initiation of ART increased the risk of HIV-DSP in the pre-cART era. Prolonged exposure to cART, PI exposure and lipid-lowering drugs (statins and fibrates) have been suggested as risk factors for neuropathy in the cART era. Height has been identified as a risk factor for PN in diabetes and recently in HIV infection when using nARTs.
Older age at the time of evaluation, taller height at parent study entry, PI use, and history of IV drug use are associated with increased risk of PN and SPN.
Associations with higher odds of PN included older patient age [OR=1.74 per 10yrs, 95%CI = (1.53, 1.97), p<0.001], taller height [OR=1.17 per 5cm, 95%CI = (1.09, 1.25), p<0.001], current PI use [OR=1.25, 95%CI = (1.06, 1.48), p=0.009], and history of IV drug use [OR=1.47, 95%CI = (1.08, 1.99), p=0.014].
Notable factors associated with higher odds of SPN included older age [OR=1.75, 95%CI = (1.49, 2.04), P<0.001], taller height [OR=1.22, 95%CI = (1.11, 1.34), P<0.001], current PI use [OR=1.58, 95%CI = (1.26, 1.99), P<0.001], and history of IV drug use [OR=1.92, 95%CI = (1.37, 2.71), P<0.001].
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