522-M. Non-Specific Immunotherapy with Murabutide Significantly Improves Responses to Recall and to HIV-1 Antigens, in Patients Naļve to Antiretroviral Therapy.

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Session 71 Poster Session
IL-2 and Other Forms of Immunotherapy
Session Time: 4:30-6:30 pm
Room 4E-F

522-M.

Non-Specific Immunotherapy with Murabutide Significantly Improves Responses to Recall and to HIV-1 Antigens, in Patients Naļve to Antiretroviral Therapy.
X. De La Tribonniere*^{1, 3}, Y. Yazdanpanah¹, Y. Mouton¹, G. M. Bahr^{2, and 3}
¹Infectious Diseases, Tourcoing; ²Pasteur Inst., Lille; and ³ISTAC Biotech, Lille, France

Background: The synthetic immunomodulator Murabutide (MB) has been reported to enhance non-specific immune defense mechanisms, to regulate cytokine synthesis, and to control HIV-1 replication in antigen-presenting cells.
Method: Following successful phase I studies in HIV-1 patients, we carried out a comparative trial on 18 patients chronically infected with HIV-1 (9 controls and 9 treated sc. with 7 mg/day of MB, 5 days/week for a period of 6 weeks) to address the potential immune benefits of non-specific immunotherapy in such patients. All patients had not received antiretrovirals and presented CD4 counts>500 cells/µL and viral load (VL) <30 000 copies/mL.
Results: Administration of MB was well tolerated in 7 out of 9 patients, and adverse reactions were spontaneously reversible upon drug interruption. No deleterious effects on VL and CD4 counts were observed throughout the whole study period (up to 18 weeks after starting MB administrations). Improvement in functionnal immune assays were noted only in MB recipients. Concerning lymphoproliferative assays, we observed a general enhancement in the size of responses to 5 different recall antigens, and significant differences between the 2 groups were achieved at week 18 against CMV antigen. Also, we observed at week 18 an increase in the size of responses to HIV proteins in the MB group (against p24 and against gp160, p<0.01), as well as a significant increase in the percentage of responders to p24 and to Nef (p<0.05). Analysis of cytokine release, before and after MB treatment, revealed an increase in the capacity of PBMCs to secrete IFN-gamma following mitogenic stimulation. No major changes in phenotypic markers of lymphocytes and monocytes could be detected in either group.
Conclusions: This pilot study points to the capacity of MB to potentiate immune responses to recall antigens as well as the recognition of viral proteins in HIV-1 patients naļve to antiretroviral therapy. Moreover, these results open new avenues for extending the use of non-specific immunotherapy to different settings including structured treatment interruptions.