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

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dc.contributor.authorVan der Watt, Johan J
dc.contributor.authorWilkinson, Katalin A
dc.contributor.authorWilkinson, Robert J
dc.contributor.authorHeckmann, Jeannine M
dc.date.accessioned2015-07-30T04:10:52Z
dc.date.available2015-07-30T04:10:52Z
dc.date.issued2014-02-10
dc.date.updated2015-01-15T17:53:54Z
dc.description.abstractAbstract 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 naïve 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.
dc.identifier.apacitationVan der Watt, J. J., Wilkinson, K. A., Wilkinson, R. J., & Heckmann, J. M. (2014). Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study. <i>BMC Infectious Diseases</i>, http://hdl.handle.net/11427/13627en_ZA
dc.identifier.chicagocitationVan der Watt, Johan J, Katalin A Wilkinson, Robert J Wilkinson, and Jeannine M Heckmann "Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study." <i>BMC Infectious Diseases</i> (2014) http://hdl.handle.net/11427/13627en_ZA
dc.identifier.citationVan der Watt, J. J., Wilkinson, K. A., Wilkinson, R. J., & Heckmann, J. M. (2014). Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study. BMC infectious diseases, 14(1), 71.
dc.identifier.ris TY - Journal Article AU - Van der Watt, Johan J AU - Wilkinson, Katalin A AU - Wilkinson, Robert J AU - Heckmann, Jeannine M AB - Abstract 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 naïve 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. DA - 2014-02-10 DB - OpenUCT DO - 10.1186/1471-2334-14-71 DP - University of Cape Town J1 - BMC Infectious Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study TI - Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study UR - http://hdl.handle.net/11427/13627 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13627
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2334-14-71
dc.identifier.vancouvercitationVan der Watt JJ, Wilkinson KA, Wilkinson RJ, Heckmann JM. Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study. BMC Infectious Diseases. 2014; http://hdl.handle.net/11427/13627.en_ZA
dc.language.rfc3066en
dc.publisher.departmentDivision of Neurologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderVan der Watt et al.; licensee BioMed Central Ltd.
dc.rights.urihttp://creativecommons.org/licenses/by/2.0*
dc.sourceBMC Infectious Diseasesen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcinfectdis/
dc.subject.otherHIV neuropathyen_ZA
dc.subject.otherSensory neuropathyen_ZA
dc.subject.otherNeuropathic symptomsen_ZA
dc.subject.otherAntiretroviral toxicityen_ZA
dc.subject.otherCytokinesen_ZA
dc.titlePlasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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