dc.contributor.author | Winckelmann, AA | |
dc.contributor.author | Munk-Petersen, LV | |
dc.contributor.author | Rasmussen, TA | |
dc.contributor.author | Melchjorsen, J | |
dc.contributor.author | Hjelholt, TJ | |
dc.contributor.author | Montefiori, D | |
dc.contributor.author | Ostergaard, L | |
dc.contributor.author | Sogaard, OS | |
dc.contributor.author | Tolstrup, M | |
dc.date.accessioned | 2020-12-22T06:13:56Z | |
dc.date.available | 2020-12-22T06:13:56Z | |
dc.date.issued | 2013-04-26 | |
dc.identifier | pii: PONE-D-12-38578 | |
dc.identifier.citation | Winckelmann, 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.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/11343/258437 | |
dc.description.abstract | Toll-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.language | English | |
dc.publisher | PUBLIC LIBRARY SCIENCE | |
dc.title | Administration of a Toll-Like Receptor 9 Agonist Decreases the Proviral Reservoir in Virologically Suppressed HIV-Infected Patients | |
dc.type | Journal Article | |
dc.identifier.doi | 10.1371/journal.pone.0062074 | |
melbourne.affiliation.department | Doherty Institute | |
melbourne.source.title | PLoS One | |
melbourne.source.volume | 8 | |
melbourne.source.issue | 4 | |
dc.rights.license | CC BY | |
melbourne.elementsid | 1195936 | |
melbourne.contributor.author | Rasmussen, Thomas | |
dc.identifier.eissn | 1932-6203 | |
melbourne.accessrights | Open Access | |