A phase I study of a six-week cycle of immunotherapy with Murabutide in HIV-1 patients naive to antiretrovirals

Med Sci Monit. 2003 Jun;9(6):PI43-50.

Abstract

Background: Limitations in the use of antiretroviral therapy suggest the need for additional approaches to enhance immune restoration and the control of HIV-1 replication. Therefore, we evaluated the clinical tolerance and biological effects of immunotherapy with the synthetic immunomodulator Murabutide in 9 treatment-naive HIV-1 patients presenting with CD4+ lymphocyte counts >500 cells/mm3 and plasma viral loads <30.000 copies/ml.

Material/methods: Murabutide was administered at a daily dose of 7 mg on 5 consecutive days per week, for a period of 6 weeks. The study duration extended over 22 weeks, and clinical, virological, and immunological evaluations were carried out on 2 occasions before, during, and after immunotherapy.

Results: With acceptable clinical tolerance and only 2 reversible grade III adverse events, clinical and virological parameters remained highly stable throughout the study period. However, maintained or improved lymphoproliferative responses to several recall and HIV-1 antigens, as well as modest but significant increases in the percentages of naive cells were noted during or/and after immunotherapy. These changes could not be demonstrated in an observation group of 9 additional patients who were identically followed for a 22-week period.

Conclusions: Our results suggest that non-specific immunotherapy targeting dysfunctions in innate immunity could bring about restoration of immune responses in HIV disease.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / administration & dosage
  • Acetylmuramyl-Alanyl-Isoglutamine / analogs & derivatives*
  • Acetylmuramyl-Alanyl-Isoglutamine / toxicity*
  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / immunology
  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / toxicity*
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • Antigens, CD / blood
  • Antigens, CD / drug effects
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Humans
  • Injections, Subcutaneous
  • Lymphocyte Activation / drug effects

Substances

  • Adjuvants, Immunologic
  • Anti-HIV Agents
  • Antigens, CD
  • Acetylmuramyl-Alanyl-Isoglutamine
  • murabutide