It's not possible to definitively say that people developed pancreatitis from taking lopinavir, as some were also taking other therapies known to cause pancreatitis like pentamidine, ddI (didanosine, Videx) and/or d4T (stavudine, Zerit). Additionally, some volunteers had very high triglyceride levels, which can result in pancreatitis. Nevertheless, people on lopinavir should carefully check their amylase levels (a marker for pancreatitis).
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GMHC Treatment Issues - Vol. 10, No. 12, Dec. 1996
[Note: Although this article is dated 1996, the information is still current and relevant therapy.]
The reverse transcriptase enzyme, which converts HIV's RNA gene set into DNA before the virus inserts itself into cells nuclei, often has been compared to a hand, complete with a palm, fingers and thumb. The fingers and thumb grab a hold of the nucleotide building blocks and attach them to the growing strand of HIV DNA, lying in the "palm" of the enzyme. This analogy was first made several years back, when the three-dimensional structure of the reverse transcriptase enzyme was discovered.
Knowing the enzyme's structure could have important implications in the design of new, more potent reverse transcriptase inhibitors. Ten years ago, discovery of the three-dimensional structure of the protease enzyme led to the discovery and development of protease inhibitors.
A group at State University of New York (SUNY), Buffalo has used reverse transcriptase structure to design a chemical, DNP poly-A, that fills the entire nucleotide binding region of the enzyme, in a fashion similar to how protease inhibitors fill the active site of the protease enzyme. When DNP poly-A was added to HIV-exposed cells, the cells did not become infected.
DNP poly-A is a sequence of nucleotides (an oligonucleotide). Usually, if strands of such material are found floating around in the blood or outside of protected areas like the cell nucleus or mitochondria, they are treated by the body as noxious garbage or enemy viral genes and quickly destroyed by special enzymes. Most oligonucleotide drugs similarly are broken down before they can reach their targets. The researchers from SUNY do not believe that this will be a problem with DNP poly-A, because the drug was stable even after prolonged incubation in cell cultures with a variety of enzymes known to cut up strands of nucleotides.
Next, the researchers administered the drug as an injection to mice with murine leukemia virus, which has a reverse transcriptase enzyme very similar to HIV's. Viral load dropped to undetectable levels in the mouse blood, and there was little toxicity. One problem with the compound, is that even though the team has modified it to increase its absorption from the digestive tract, it still looks as though DNP poly-A will have to be administered as an injection.
There is no word yet if any pharmaceutical company is interested in developing this compound.
Back to the What's New? November, 2000 Table of Contents.