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AIDS at 20: Is there light at the end of the tunnel?

This week marked the twentieth anniversary of the AIDS epidemic. On June 5, 1981, doctors in Los Angeles reported five unusual cases of immune system failure, all gay young men. These were the first reported cases of AIDS.

A tragic flood of additional cases have followed. In the twenty years since that day, the United States has recorded 758,000 AIDS cases and 438,000 AIDS deaths. Worldwide, the figures are numbing: 60 million cases and 22 million dead. Three million people died of AIDS last year alone, most in sub-Saharan Africa.

Faced with this plague -- no other word will do -- scientists all over the world have sought a way to fight the HIV virus that causes the disease. It has been a discouraging battle.

Initial attempts to prepare a vaccine focused on the outside skin of the virus, made of protein units called gp120 slotted together like bricks in a wall. Initial tests of gp120 vaccines were not encouraging, however, as the HIV virus genes mutate a lot (that is, they undergo random changes, like the typos of a bad typist). A vaccine against one version of gp120 may not work against another, and few people have exactly the same version. Nevertheless, two gp120 vaccines are in stage III clinical trials, in case they might help some people.

Other approaches that initially seemed promising have failed as well. Clusters of people thought immune to AIDS proved not to be. Live HIV vaccines with a disabled nef gene, thought to be safe, proved not to be. Hope has, time and again, paled to disappointment.

After 20 years of trial and failure, it is not easy to be optimistic about new candidate approachs. However, a burst of AIDS-related advances in the last year has once again teased researchers with the seductive excitement of progress. Everything is very tentative, and research teams do not wish to spark false hope. Still, throwing caution to the winds, lets explore these promising new approaches.

Creating an AIDS Vaccine That Works. The high mutability of the HIV virus can be circumvented with a vaccine that is directed at several genes, not just gp120 alone. A random mutation that alters one gene will not randomly occur in other genes at the same time -- lightening rarely strikes the same tree twice, and never three times. These multigene vaccines are very promising in trials involving laboratory animals, and phase I human clinical trials are due to begin next year.

Other promising vaccines employ a double-barreled approach, activating cell-mediated immunity as well as antibody defenses. Still others use novel proteins to boost the human immune response, or target particularly nonmutable portions of the HIV genome.

Should we be hopeful? The experts are. In an explosion of expensive investment by pharmaceutical companies banking on the promise of these approaches, fully nineteen different AIDS vaccine clinical trials will be underway by this time next year!

Preventing HIV Infections From Reaching the Immune System In the First Place. The sexual transmission of HIV could be blocked if the dendritic cells that transport HIV from its point of entry (the cells lining the mouth, vagina, and rectum) to where the immune system resides (the lymph nodes) could be persuaded not to do so. Researchers have identified the special protein on dendritic cells that binds to gp120 on HIV. They are now searching for a way to block this dendritic protein, and so frustrate any HIV infection.

Preventing HIV from Entering an Immune System Cell. To enter and kill an immune system cell, HIV first binds a receptor protein on the immune cell surface called CD-4. Thus stuck to the cell surface, HIV is shoved up against an adjacent “co-receptor” protein. It is HIV’s nudging this co-receptor that actually triggers the virus’s entry into the cell. Your body doesn’t seem harmed by destruction of the co-receptor, and many labs are exploring ways to block it, such as sticking antibodies to it.

Preventing HIV From Leaving Infected Cells. HIV leaves infected cells by budding out. Bits of the cell surface protrude like warts, then pinch off, forming tiny spheres of membrane with virus inside. The exit process is triggered when the gp120 protein of the virus links itself to a cell protein called ubiquitin, which functions as a door bell to signal that protrusion should start. Researchers are looking for a way to inhibit the enzyme that links gp120 to ubiquitin. Such an inhibitor would trap HIV within already-infected cells, and so prevent its spread to others.

With AIDS, history has taught us that hope is rarely rewarded. This year, just maybe, history will be wrong.

©Txtwriter Inc.





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