Life Lines 98 -- What are protease inhibitors?

We hear about AIDS patients taking multiple medications to prevent their infected white blood cells from making new HIV particles. One of those agents directly damages virus DNA; it can, alas, also damage human DNA. The other major agent is called a protease inhibitor. Proteases are proteins that act as enzymes to cleave certain proteins the virus makes.
The HIV chromosome has several genes. When the virus enters a white blood cell, it converts its RNA chromosome into a DNA chromosome. The DNA chromosome then enters the cell nucleus and inserts itself. Occasionally, some of its genes are decoded back to RNA. At one end of the virus chromosome, two such regions are copied as a single thread and they are in turn decoded into a long protein. That long protein is chopped into six smaller pieces by an enzyme from another part of the virus chromosome. That enzyme is a protease.
If there is no protease in the cell, then defective viruses are put together and they can’t infect cells. A protease inhibitor prevents protease from cutting up the virus proteins into its needed pieces. It does not kill already infected cells.
Protease inhibitors are very effective and they can prevent viruses from being made as long as the body is supplied with protease inhibitors. If the person stops using protease inhibitors, then the virus chromosomes that were inserted into the white blood cells will resume making viruses.
The optimistic hope is that the body will have enough time to rebuild its immune system and take care of such new viruses if protease inhibitors are no longer given. The pessimistic expectation is that the virus would ultimately come back strong and to prevent it, protease inhibitors must be given for life. So far, neither view is a clear winner. It costs about $4,000 to $6,000 per year to supply one patient with protease inhibitors. There are four different protease inhibitors that have been synthesized and approved for medical prescription. The cost is high because the inhibitors are complex molecules that are difficult to manufacture. Add to that the tens of millions of dollars spent to prove that the drug will not make the patient sicker and to prove that it really does what it claims it does, and you can readily see how some drugs are worth their weight in rare postage stamps.
Now that protease inhibitors have been used for several years, AIDS patients who thought they would be dead in a year are suddenly finding that they can work again and are making plans for the coming years. They are also discovering some long-term side effects, including a curious deposit of fat around the viscera making their abdomens bulge.
The fight to eliminate AIDS will be a long one. There are over 30 million cases worldwide and for the near future we will see several tens of thousands of new cases in the United States. Many countries are still not taking measures to prevent the spread of AIDS, many of them hoping a vaccine will be found to solve the problem. There are many such vaccines in the works but each has its own uncertainty about how well it will work. Any virus that makes the immune system its meal ticket has a lot of skills getting through those defenses.