Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART

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dc.contributor.authorKampmann, B
dc.contributor.authorTena, G
dc.contributor.authorNicol, MP
dc.contributor.authorLevin, M
dc.contributor.authorEley, BS
dc.date.accessioned2018-10-02T08:31:51Z
dc.date.available2018-10-02T08:31:51Z
dc.date.issued2006
dc.date.updated2016-03-30T11:41:11Z
dc.description.abstractObjective: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. Design: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette–Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. Patients: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. Results: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-γ levels in culture supernatants did not reflect this response; however, a decline in TNF-α was observed. Conclusion: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.
dc.identifierhttp://dx.doi.org/10.1097/01.aids.0000222073.45372.ce
dc.identifier.apacitationKampmann, B., Tena, G., Nicol, M., Levin, M., & Eley, B. (2006). Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART. <i>AIDS</i>, http://hdl.handle.net/11427/28905en_ZA
dc.identifier.chicagocitationKampmann, B, G Tena, MP Nicol, M Levin, and BS Eley "Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART." <i>AIDS</i> (2006) http://hdl.handle.net/11427/28905en_ZA
dc.identifier.citationKampmann, B., Tena-Coki, G. N., Nicol, M. P., Levin, M., & Eley, B. (2006). Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART. Aids, 20(7), 1011-1018.
dc.identifier.ris TY - AU - Kampmann, B AU - Tena, G AU - Nicol, MP AU - Levin, M AU - Eley, BS AB - Objective: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. Design: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette–Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. Patients: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. Results: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-γ levels in culture supernatants did not reflect this response; however, a decline in TNF-α was observed. Conclusion: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART. DA - 2006 DB - OpenUCT DP - University of Cape Town J1 - AIDS LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART TI - Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART UR - http://hdl.handle.net/11427/28905 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/28905
dc.identifier.vancouvercitationKampmann B, Tena G, Nicol M, Levin M, Eley B. Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART. AIDS. 2006; http://hdl.handle.net/11427/28905.en_ZA
dc.language.isoeng
dc.publisher.departmentPaediatrics and Child Health
dc.publisher.facultyFaculty of Health Sciences
dc.publisher.institutionUniversity of Cape Town
dc.sourceAIDS
dc.source.urihttp://www.ovid.com/site/index.jsp
dc.subject.otherchildren
dc.subject.otherHIV
dc.subject.othertuberculosis
dc.subject.otherimmune responses
dc.subject.otherHAART
dc.titleReconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART
dc.typeJournal Article
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uct.type.filetypeText
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