PloS one, 2013-04, Vol.8 (4), p.e62074-e62074
2013
Details
- Autor(en) / Beteiligte
- Titel
- Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients
- Ist Teil von
- PloS one, 2013-04, Vol.8 (4), p.e62074-e62074
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0062074Titel-ID: cdi_plos_journals_1346593227
- Format
- –
- Schlagworte
- Acquired immune deficiency syndrome, Adult, Adults, AIDS, AIDS vaccines, Antibodies, Antiretroviral agents, Antiretroviral drugs, Antiretroviral therapy, Antiviral agents, Biology, CD4 antigen, CD4-Positive T-Lymphocytes - drug effects, CD4-Positive T-Lymphocytes - immunology, CD4-Positive T-Lymphocytes - virology, CD8 antigen, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - virology, Cell Compartmentation - drug effects, CpG islands, Degranulation, Deoxyribonucleic acid, Disease Reservoirs - virology, DNA, Highly active antiretroviral therapy, HIV, HIV (Viruses), HIV Antibodies - biosynthesis, HIV infection, HIV Infections - drug therapy, HIV Infections - immunology, HIV Infections - virology, HIV patients, Human immunodeficiency virus, Humans, Immune system, Immunity, Immunity - drug effects, Immunization, Immunologic Memory - drug effects, In vivo methods and tests, Inflammation, Latency, Latent infection, Load distribution, Lymphocytes, Lymphocytes T, Macrophage inflammatory protein, Macrophages, Medicine, Middle Aged, Oligodeoxyribonucleotides - administration & dosage, Oligodeoxyribonucleotides - pharmacology, Oligodeoxyribonucleotides - therapeutic use, Patients, Phenotype, Proteins, Proviruses - drug effects, Randomization, Species Specificity, Stress concentration, T cell receptors, T cells, TLR9 protein, Toll-Like Receptor 9 - agonists, Toll-Like Receptor 9 - metabolism, Toll-like receptors, Vaccination, Vaccines, Viral antibodies, Viral Load - drug effects