The leaves of the pokeweed plant contain a protein with antiviral activity called PAP (pokeweed antiviral protein). This protein can attack herpes viruses and HIV. When PAP joins with a certain antibody called TXU, it is carried to T-cells and macrophages. These cells are an important part of the immune system and are attacked by HIV. Once TXU attaches itself to these cells, it releases PAP, and PAP then enters the cell. Inside the cell, PAP damages HIV's genetic material and blocks the HIV-infected cell from producing new viruses.
This combination of antibody and protein is called TXU-PAP. Researchers at the Hughes Institute, St. Paul, Minnesota, have been studying this product for several years and have released very early results from a short study in HIV- infected subjects. According to their data, an infusion of TXU-PAP can reduce viral load and significantly raise levels of important virus-fighters called natural killer cells (NK). It is clear, however, that further study is needed to find out how often the drug needs to be taken and at what dose.
Researchers enrolled nine adult HIV-positive subjects (four females, five males). Various combinations of anti-HIV drugs had failed to help these subjects. Six of the nine subjects agreed to remain in the study so that their blood could be collected and analysed regularly. The results presented here are based on those of these six subjects. When they entered the study, subjects had an average CD4+ count of 320 cells and viral load of about 220,000 copies. Before they received the infusion of TXU-PAP, subjects took the antihistamine Benadryl along with the pain reliever, Tylenol, to reduce the risk of allergic reactions and fever. Nurses infused TXU-PAP into a vein at a dose of 5 micrograms per kilogram over one hour. This dose of TXU-PAP is generally considered too low to cause sustained anti-HIV activity. The researchers, however, appeared to be more concerned with the possible toxicity of the product in people with HIV infection.
One day after receiving the infusion, viral loads fell dramatically in most subjects (in one case there was a 100-fold reduction). In only one case did viral load fall below the 500 copy mark. Keeping in mind that no subject was taking prescribed antiretroviral drugs and that all subjects only received a single low-dose of TXU-PAP, the results seem remarkable. Four weeks after their infusion, subjects' viral loads were 13 to 50 per cent below their pre-study level.
CD4+ counts increased in some subjects and declined in others, so a clear trend did not emerge. Natural killer cell levels increased significantly in all six subjects. Ultimately, this occurrence may be important, because NK cells can have anti-HIV activity. No data on CD8+ cell counts were released.
The researchers' next step is to find out whether subjects can tolerate higher and more frequent doses of TXU-PAP. A study where subjects will receive daily infusions of TXU-PAP for 10 consecutive days is under way.
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2. Rajamohan F, Venkatachalam TK, Irving JD, Ukun FM. Pokeweed antiviral protein isoforms PAP-1, PAP-II, and PAP-III depurinate RNA of human immunodeficiency virus (HIV-1). Biochemical and Biophysical Research Communications 1999;5:260(2):453-458.
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