Clinical and immunological effects of a 6 week immunotherapy cycle with murabutide in HIV-1 patients with unsuccessful long-term antiretroviral treatment.
In an effort to evaluate the potential of non-specific immunotherapy in restoring global immunity, we have examined the clinical tolerance and biological effects of a 6 week administration of the immunomodulator, murabutide, in chronically infected HIV-1 patients. Forty-two subjects, presenting weak immune reconstitution and ineffective virus suppression following long-term highly active antiretroviral therapy (HAART), were randomized to receive, or not, murabutide 7 mg/day on five consecutive days/week. Clinical and immunological parameters were monitored before and after the immunotherapy period. Administration of murabutide was generally well tolerated, although some grade III adverse events, reversible on treatment cessation, were observed. Interestingly, in comparison with pre-inclusion levels, at 1 week after the immunotherapy cycle, only murabutide recipients presented a significant increase in CD4 cells, platelet counts, and in the percentage of patients with undetectable viral loads (<50 copies/mL). Statistical significance between the two groups was only evident with the latter parameter. Some of these clinical changes were maintained even up to 12 weeks after murabutide administration, and were accompanied by an increased ability to mount cellular responses to active immunization with a recall antigen, and by a significant increase in the percentage of patients presenting positive lymphoproliferative responses to the viral antigen gp160. These results warrant further evaluation of extended periods or cycles of murabutide immunotherapy as adjunct to HAART.
Bahr
George M
GM
Laboratory of Molecular Immunology of Infection and Inflammation, Pasteur Institute of Lille, 1 rue du Professeur Calmette, BP 245, 59019 Lille Cédex, France. georges.bahr@pasteur-lille.fr
De La Tribonniere
Xavier
X
Darcissac
Edith
E
Ajana
Faïza
F
Bocket
Laurence
L
Sissoko
Daouda
D
Yazdanpanah
Yazdan
Y
Dewulf
Joëlle
J
Amiel
Corinne
C
Mouton
Yves
Y
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000704:Analysis of Variance; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods / Q000706:statistics & numerical data; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000706:statistics & numerical data; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D010865:Pilot Projects; D011971:Receptors, Immunologic / Q000378:metabolism; D018709:Statistics, Nonparametric
D000276:Adjuvants, Immunologic; D044966:Anti-Retroviral Agents; D016207:Cytokines; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C033575:murabutide