Clinical tolerance and immunologic effects after single or repeated administrations of the synthetic immunomodulator murabutide in HIV-1-infected patients.
Correction of the virus-induced deficits in innate immunity of HIV-infected subjects could well contribute to enhanced immune recovery and efficacious control of viral replication. The safe synthetic immunomodulator Murabutide (ISTAC Biotechnology, Lille, France) has been found to regulate the function of antigen-presenting cells and to selectively activate CD4 lymphocytes leading to dramatic suppression of HIV replication, in vitro. Therefore, as a first step toward the evaluation of the immunotherapeutic potential of Murabutide in HIV disease, we have conducted two phase 1/2 clinical trials to address the safety and the immunologic effects of Murabutide administration into HIV-infected subjects receiving antiretroviral therapy. The first study revealed that single administration of 5, 7, or 9 mg of Murabutide, to 6 patients per dose, was well tolerated. This was accompanied by a selective induction of cytokines and chemokines detectable in the serum, and the levels appeared to plateau at the 7-mg dose. The second study then evaluated the safety and biological effects of repeated administrations of 7 mg Murabutide, on 5 consecutive days, in 12 HIV-1-infected patients. A good clinical tolerance was noted throughout the study. Moreover, changes in several immune parameters, including downregulation of coreceptor expression on lymphocytes and improved lymphoproliferative responses, were detected during or/and up to 3 weeks after Murabutide administration. These encouraging results warrant further evaluation of longer periods or cycles of immunotherapy with Murabutide in HIV-infected subjects.
Infectious Disease Department of Tourcoing Hospital, Northern AIDS Reference Center, Lille, France.
Corinne
C
Amiel
Xavier
X
De La Tribonnière
Vincent
V
Vidal
Edith
E
Darcissac
Yves
Y
Mouton
George M
GM
Bahr
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000009:adverse effects*; D000328:Adult; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000097:blood; D005260:Female; D015497:HIV-1; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D015375:Receptors, Interleukin-2; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide