Neuropathy After Beginning HIV Medication

Today's post from biomedcentral.com (see link below) is a complex technical research article looking at how and why so many people develop neuropathic symptoms shortly after beginning HIV medications. It's not easy to understand for the layman but clicking on the PDF link at the end will give those who are interested, the full story. What this article does do is confirm the link between HIV meds and neuropathy. It has long been known that older HIV meds can be responsible for causing nerve damage but the jury's out regarding newer treatments. This article may fill in some gaps for some people.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study 

Research article
Johan J van der Watt, Katalin A Wilkinson, Robert J Wilkinson and Jeannine M Heckmann BMC Infectious Diseases 2014, 14:71 doi:10.1186/1471-2334-14-71 Published: 10 February 2014

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Abstract (provisional)
Background

In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study.
Methods

One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays.
Results

Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002).

Conclusions

The initiation of cART in previously treatment naive individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
 
http://www.biomedcentral.com/1471-2334/14/71/abstract