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dc.contributor.authorWinckelmann, AA
dc.contributor.authorMunk-Petersen, LV
dc.contributor.authorRasmussen, TA
dc.contributor.authorMelchjorsen, J
dc.contributor.authorHjelholt, TJ
dc.contributor.authorMontefiori, D
dc.contributor.authorOstergaard, L
dc.contributor.authorSogaard, OS
dc.contributor.authorTolstrup, M
dc.date.accessioned2020-12-22T06:13:56Z
dc.date.available2020-12-22T06:13:56Z
dc.date.issued2013-04-26
dc.identifierpii: PONE-D-12-38578
dc.identifier.citationWinckelmann, A. A., Munk-Petersen, L. V., Rasmussen, T. A., Melchjorsen, J., Hjelholt, T. J., Montefiori, D., Ostergaard, L., Sogaard, O. S. & Tolstrup, M. (2013). Administration of a Toll-Like Receptor 9 Agonist Decreases the Proviral Reservoir in Virologically Suppressed HIV-Infected Patients. PLOS ONE, 8 (4), https://doi.org/10.1371/journal.pone.0062074.
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11343/258437
dc.description.abstractToll-like receptor (TLR) agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a double-blind randomized controlled vaccine trial. HIV-infected adults were randomized 1:1 to receive pneumococcal vaccines with or without 1 mg CPG 7909 as adjuvant at 0, 3 and 9 months. In patients on suppressive antiretroviral therapy we quantified proviral DNA at 0, 3, 4, 9, and 10 months (31 subjects in the CPG group and 37 in the placebo-adjuvant group). Furthermore, we measured HIV-specific antibodies, characterized T cell phenotypes and HIV-specific T cell immunity. We observed a mean reduction in proviral DNA in the CPG group of 12.6% (95% CI: -23.6-0.0) following each immunization whereas proviral DNA in the placebo-adjuvant group remained largely unchanged (6.7% increase; 95% CI: -4.2-19.0 after each immunization, p = 0.02). Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1β (MIP1β) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant. Further, increasing proportion of HIV-specific CD107a and MIP1β-expressing CD8+ T cells were strongly correlated with decreasing proviral load. No changes were observed in T cell phenotype distribution, HIV-specific CD4+ T cell immunity, or HIV-specific antibodies. TLR9-adjuvanted pneumococcal vaccination decreased proviral load. Reductions in proviral load correlated with increasing levels of HIV specific CD8+ T cells. Further investigation into the potential effect of TLR9 agonists on HIV latency is warranted.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleAdministration of a Toll-Like Receptor 9 Agonist Decreases the Proviral Reservoir in Virologically Suppressed HIV-Infected Patients
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pone.0062074
melbourne.affiliation.departmentDoherty Institute
melbourne.source.titlePLoS One
melbourne.source.volume8
melbourne.source.issue4
dc.rights.licenseCC BY
melbourne.elementsid1195936
melbourne.contributor.authorRasmussen, Thomas
dc.identifier.eissn1932-6203
melbourne.accessrightsOpen Access


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