Objective: Immune reconstitution in highly active antiretroviral therapy (HAART)-treated individuals is incomplete and immunomodulatory compounds are needed to improve the outcome of HIV therapy. In a Phase I/II clinical trial performed on HIV-positive patients we analysed the safety and immunomodulating effects of tucaresol, a novel compound that has previously been described to enhance cell-mediated immune responses. Patients and methods: Sixteen weeks pulse dose escalation protocol. Four groups of HIV-positive patients were enrolled: group A (n = 6): HAART, CD4+ 300 - 500 cells/mu l, HIV RNA < 80 copies/ml; group B (n = 6): HAART-naive, CD4+ < 500 cells/ mu l, HIV RNA > 10000 copies/ml; group C (n = 3): HAART-naive, CD4+ > 500 cells/ mu l, HIV RNA < 10000copies/ml; and group D (n = 6): HAART, CD4+ < 200cells/mu l, HIV RNA < 80copies/ml. Tucaresol was added to HAART in group A and D patients; group B patients started tucaresol with HAART, group C patients received tucaresol alone. Clinical and immunological analyses were performed at different time points. Results: Tucaresol-related serious adverse events were observed in the first week of therapy in 2/21 patients who were viraemic when commencing treatment, but did not occur in patients on stable HAART. Tucaresol did not affect HIV viraemia whereas increases in CD4+ percentages, mainly supported by naive CD4+ cells, were observed. CD8+/28-/45RA+ cells and HIV-specific CD8+ IFN gamma- and perforin-producing cells improved whereas IL-10 mRNA diminished in tucaresol-treated patients. The effects were greater with 25 mg given every other day for 1 week. Conclusion: In HAART-receiving patients with proper virus suppression, tucaresol was not associated with serious adverse events and resulted in qualitative and quantitative stimulation of HIV-specific cytotoxic T lymphocyte activity and generation of naive T cells. These data may support further exploration of tucaresol use in reconstitution of immune system parameters in HIV patients with proper virus suppression while on HAART.
|Titolo:||Immunomodulation induced by tucaresol in HIV infection: results of a 16 week pilot Phase I/II trial|
|Autori interni:||GALLI, MASSIMO|
TRABATTONI, DARIA LUCIA (Secondo)
MARCHETTI, GIULIA CARLA
CLERICI, MARIO SALVATORE (Ultimo)
|Parole Chiave:||active antiretroviral therapy; virus type-1 infection; I-restricted presentation; cytotoxic T-lymphocytes; base-forming drugs; protease inhibitor; granule exocytosis; cell-activation; immune-system; viral load|
|Settore Scientifico Disciplinare:||Settore MED/17 - Malattie Infettive|
Settore BIO/13 - Biologia Applicata
Settore MED/04 - Patologia Generale
Settore MED/07 - Microbiologia e Microbiologia Clinica
|Data di pubblicazione:||2004|
|Appare nelle tipologie:||01 - Articolo su periodico|
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