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Peripheral Neuropathy in Primary HIV Infection Associates With Systemic and Central Nervous System Immune Activation

Wang, Samantha X.Y. BA*; Ho, Emily L. MD, PhD; Grill, Marie MD; Lee, Evelyn BA; Peterson, Julia BS; Robertson, Kevin PhD§; Fuchs, Dietmar PhD; Sinclair, Elizabeth PhD; Price, Richard W. MD; Spudich, Serena MD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2014 - Volume 66 - Issue 3 - p 303–310
doi: 10.1097/QAI.0000000000000167
Clinical Science

Background: Peripheral neuropathy (PN) is a frequent complication of chronic HIV infection. We prospectively studied individuals with primary HIV infection (<1 year after transmission) to assess the presence of and laboratory associations with PN in this early stage.

Methods: Standardized examination and analysis of blood and cerebrospinal fluid (CSF) was performed in participants with laboratory-confirmed primary HIV infection. PN was defined as ≥1 of the following unilateral or bilateral signs: decreased distal limb position, vibration, or temperature sense or hyporeflexia; symptomatic PN (SPN) was defined as the presence of these signs with symptoms. Analysis used nonparametric statistics.

Results: Overall, 20 (35%) of 58 antiretroviral-naive male subjects without diabetes evaluated at a median of 107 days post HIV transmission met criteria for PN. Thirteen (65%) of 20 PN subjects met criteria for SPN; 6 (30%) of 20 had bilateral findings. PN subjects and no PN subjects (NPN) did not differ in median age, days post HIV transmission, blood CD4 or CD8 counts, CSF or plasma HIV RNA levels, CSF white blood cell counts, or CSF to blood albumin ratio. PN and SPN subjects had elevated CSF neopterin (P = 0.003 and P = 0.0005), CSF monocyte chemoattractant protein-1 (P = 0.006 and P = 0.01), and blood neopterin (P = 0.006 and P = 0.009) compared with NPN subjects. PN subjects had a higher percentage of activated phenotype CSF CD8+ T lymphocytes than NPN subjects (P = 0.009).

Conclusions: Signs of PN were detected by detailed neurologic examination in 35% of men enrolled in a neurological study at a median of 3.5 months after HIV transmission. PN during this early period may be mediated by systemic and nervous system immune responses to HIV.

*Department of Neurology, Yale University School of Medicine, New Haven, CT;

Department of Neurology, Harborview Medical Center, University of Washington Medical Center, Seattle, WA;

Department of Neurology, University of California San Francisco, San Francisco, CA;

§Department of Neurology, University of North Carolina, Chapel Hill, NC; and

Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Austria.

Correspondence to: Samantha X.Y. Wang, BA, Yale University School of Medicine, 15 York Street, New Haven, CT 06510 (e-mail:

Presented at the Conference for Retroviruses and Opportunistic Infections, March 5–8, 2012, Seattle, WA.

The current study is not industry sponsored. E.L.H. receives research royalties from Santa Cruz Biotechnology, Inc. R.W.P. has received speaker honoraria and support for meeting travel from Abbott Laboratories. He is also a consultant to Merck and Co. No activities were related to this study. K.R. is a consultant for Abbott Laboratories and ViiV/GSK. No activities were related to this study. S.S. has received support for travel to a scientific meeting and a speaker honorarium from AbbVie. The remaining authors report no disclosures.

Received October 17, 2013

Accepted February 15, 2014

© 2014 by Lippincott Williams & Wilkins