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

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.