Trichosanthin treatment of HIV-induced immune dysregulation.
Twenty patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC) or asymptomatic HIV infection (HIV+) were given 20 mcg kg-3 trichosanthin (TCS; 'Compound Q'), a ribosome-inactivating protein with in vitro antiviral activity against human immunodeficiency virus (HIV) once every four weeks for up to 12 weeks. With the concurrent administration of prostaglandin inhibitors, the drug was moderately well tolerated, with most subjects experiencing mild arthralgia, hives and malaise. Additionally, four patients experienced neurological complications which resolved spontaneously without intervention. Four of 20 subjects in this open label pilot study showed progressive although transient reductions in viral activity as measured by p-24 antigen level decreases. Subjects also experienced decreases in levels of beta 2-microglobulin. Ten HIV+ and healthy ARC subjects demonstrated improved immunological status as measured by significant increases in percentage of CD4+ cells and augmentations in delayed hypersensitivity reactions. Eight of 20 subjects reported improved appetites and increased energy levels. The group as a whole had a weight gain of 3.2 kg. Eight of 20 subjects who presented with persistent generalized lymphadenopathy exhibited a marked diminution in the size of their lymph nodes after the first treatment. No subject who presented with oral candidiasis experienced an improvement in that condition. We conclude that, in the short term, TCS seems to have the ability to reduce viral activity and improve certain symptoms in healthy ARC patients and HIV + asymptomatics although it may not be able to restore immune competence in persons with advanced AIDS or poor prognosis ARC. Additionally, the drug may pose a special risk for patients with HIV-related dementia.
Mayer
R A
RA
R. A. Mayer Clinic, Department of Research and Development, North Miami, Florida.
Sergios
P A
PA
Coonan
K
K
O'Brien
L
L
D000386:AIDS-Related Complex / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D016655:HIV Core Protein p24 / Q000097:blood; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D015978:Trichosanthin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001613:beta 2-Microglobulin / Q000378:metabolism
D016655:HIV Core Protein p24; D001613:beta 2-Microglobulin; D015978:Trichosanthin