ABSTRACT
Trichosanthin is a ribosome-inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histiocytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV-infected macrophages.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Antiviral Agents/adverse effects , Aphasia/chemically induced , Brain/pathology , Coma/chemically induced , Hemiplegia/chemically induced , Trichosanthin/adverse effects , Adult , Antiviral Agents/therapeutic use , Aphasia/pathology , Basal Ganglia/drug effects , Basal Ganglia/pathology , Brain/drug effects , Coma/pathology , Fatal Outcome , Gliosis , Hemiplegia/pathology , Humans , Male , Middle Aged , Necrosis , Trichosanthin/therapeutic useABSTRACT
Trichosanthin, a ribosomal inhibitor protein, blocks HIV replication in lymphocytes and macrophages. This agent was used to treat 51 patients with advanced HIV disease in a dose-escalation study in which three injections were administered over a 9-21-day period in a dose range of 10-30 micrograms/kg per injection. The maximum tolerated dose was estimated to be 30 micrograms/kg. Reversible but severe fatigue and myalgias were the major dose-limiting side-effects; mild leucocytosis and elevations in serum transaminases were noted and were reversible. Non-dose-related reversible mental status changes were seen in six patients and were considered to be associated with the drug. This was usually manifest as dementia, but progressed to coma in two patients. This reversed, but the sequelae resulted in death in one patient. Decreases in serum p24 antigen levels were noted 1 month after the first infusion in 10 of 18 patients who entered the study with elevated levels; one converted to negative. Values usually remained low to the end of the study period (2 months). In those patients with CD4+ cell levels greater than 50 x 10(6) cells/l significant decreases in sedimentation rate and increases in CD4+ cell numbers were also noted. These changes were found at all dose levels but only in patients receiving three infusions.
