Map of life expectancy at birth from Global Education Project.

Monday, August 29, 2005

Hoping for a technical fix

My employer is going to be recruiting people to participate in trials of HIV vaccines. Well, that's not exactly correct. Right now, there are nearly three dozen experiments underway in which humans are injected with various substances which it is hoped will stimulate an immune response of some kind to HIV. However, it is not expected that any of these will actually turn out to be a usable preventive vaccine. These are actually just experiments intended to learn more about how HIV interacts with the immune system, in the hope that the knowledge will lead to an effective strategy.

When HIV was first identified more than 20 years ago as the cause of AIDS, we heard predictions that a vaccine would be developed quickly. That we are still not much closer to that goal is partly because HIV turns out to present very difficult problems, and partly because of a problem with how we finance medical research.

The technical problems are a bit beyond the scope of this site, but to summarize as best I can:

  1. HIV's outer envelope proteins -- the targets of the immune system's antibody response to most viruses -- hide from antibodies under a cloak of sugar molecules;
  2. HIV incorporates itself into cellular DNA and can hide out there indefinitely, even while the immune system is competent to suppress the viral load in the blood stream;
  3. HIV continually mutates and can change its presentation to the immune system.
There is a possibility of a therapeutic vaccine, that could at least slow the progression of HIV disease, by stimulating another arm of the immune system, the T cells that can identify and kill HIV infected cells. Such a vaccine would not get prevent or eliminate HIV infection, nor would it completely stop progression of the disease. (Remember, for one thing, that those very infected cells that are being killed are cells of the immune system.) But perhaps, if this type of vaccine were combined with molecules that could prime the immune system to recognize HIV in the bloodstream, some protection against infection could result.

The structural problem is that we depend on drug companies for most large-scale research, and they aren't particularly interested in HIV vaccines. Of course, they're already making tons of money selling anti-retroviral drugs, which must be taken by people with HIV every day, for their entire lives. A vaccine, which people get as one shot or perhaps a brief series of shots, would be far less profitable. (I won't be so cynical as to suggest that the loss of potential revenues from anti-retroviral drugs is a factor in their thinking.) As a result, most HIV vaccine research is sponsored by the National Institute of Allergy and Infectious Diseases at NIH, and that funding is far less than drug companies spend on developing drugs with high profit potential.

There are ethical problems with HIV vaccine research as well. Most vaccines cause volunteers to test HIV positive in standard tests, which detect the presence of antibodies. This makes it much more difficult and expensive to determine in the future whether they have in fact become infected. There is also a danger that volunteers, due to misunderstanding or wishful thinking, will believe they have some protection against HIV and hence take fewer precautions against infection than they would otherwise. Since these trials are "blinded," volunteers don't know whether they have received the experimental agent or a sham injection, but for ethical reasons, volunteers in both arms need to be intensively counseled to avoid the risk of infection. Yet, for the trial to yield meaningful results, some volunteers do need to become infected.

This perplexing ethical problem makes me somewhat skeptical about whether my agency ought to be recruiting our clients to participate in these experiments. What do others think?

An HIV vaccine would be about the best news we've had in a long, long time. But the prudent thing to do is plan, and act, as though it will never come.

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