cl-075 and HIV-Infections

Despite the advances in Human Immunodeficiency Virus (HIV) treatment, the cure for all HIV patients still poses a major challenge, which needs to be surpassed in the coming years. Among the strategies pursuing this aim, the 'kick-and-kill' approach, which involves the reactivation and elimination of a latent HIV reservoir that resides in some CD4

Topics: Anti-HIV Agents; CD4-Positive T-Lymphocytes; Histone Deacetylase Inhibitors; HIV Infections; HIV-1; Humans; Molecular Structure; Virus Latency

Dendritic cell (DC) numbers and functions can be affected by HIV and HCV disease, but the effects of antiretroviral therapy (ART) on DC and the implications of these changes are unclear. We examined circulating DC in samples from Indonesian patients beginning ART with advanced HIV disease and documented mild/moderate HCV hepatitis. Frequencies of myeloid and plasmacytoid DC increased after 6 months on ART, but frequencies of DC producing IL-12 or IFNα following stimulation with TLR agonists (CL075, CpG) did not change. IFNγ responses to CL075, HCV and other antigens rose over this period. Hence increased IFNγ responses during ART may be associated with increased DC frequencies rather than changes in their functional capacity.

Topics: Adolescent; Adult; Antiretroviral Therapy, Highly Active; Arthritis, Infectious; Cells, Cultured; Coinfection; Cytokines; Dendritic Cells; Hepacivirus; Hepatitis C; HIV; HIV Infections; Humans; Indonesia; Male; Middle Aged; Quinolines; Thiazoles; Young Adult

Amongst HIV patients with successful virological responses to antiretroviral therapy (ART), poor CD4(+) T-cell recovery is associated with low nadir CD4(+) T-cell counts and persistent immune activation. These factors might be influenced by dendritic cell (DC) function. Interferon-α-producing plasmacytoid DC and IL-12-producing myeloid DC were quantified by flow cytometry after stimulation with agonists to TLR7/8 (CL075) or TLR9 (CpG-ODN). These were compared between patients who achieved CD4(+) T-cell counts above or below 200 cells/μL after 6 months on ART (High vs. Low groups). High Group patients had more DC producing interferon-α or IL-12 at Weeks 6 and 12 on ART than Low Group patients. The frequencies of cytokine-producing DC at Week 12 were directly correlated with CD4(+) T-cell counts at baseline and at Week 12. Patients with good recovery of CD4(+) T-cells had robust TLR-mediated interferon-α responses by plasmacytoid DC and IL-12 responses by myeloid DC during early ART (1-3 months).

Topics: ADP-ribosyl Cyclase 1; Adult; Anti-Retroviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Dendritic Cells; HIV Infections; HLA-DR Antigens; Humans; Interferon-alpha; Interleukin-12; Leukocyte Count; Lymphocyte Activation; Male; Membrane Glycoproteins; Middle Aged; Oligodeoxyribonucleotides; Quinolines; Thiazoles; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptor 9