NECSI Guide: About Complex Systems

HIV Infection: Studying Dynamic Response

In the late 1980s and early 1990s HIV infection was known to cause AIDS. However, this process of infection involved a long "latent" period which could extend for many years. This latent period had little or no symptoms of disease. There was an ongoing debate about whether treatment of the infection should begin during the latent period, or only when the terrible symptoms of immune deficiency began. During the latent period the level of HIV measured in the blood of an infected person was found to be nearly constant over long periods of time. It seemed as if not much was happening.

"In the early 1990s a new set of drugs known as protease inhibitors were being studied. These drugs inhibit the production of HIV but do not affect it once it has been produced. Alan Perelson, a theoretical immunologist, who is part of the complex systems community, suggested to David Ho a well known AIDS researcher, that the dynamic response should be measured. This involved measuring the HIV concentration at frequent intervals after treatment with the protease inhibitor began. Originally measuring at daily intervals they found that the level of HIV was dramatically reduced and then recovered over a longer period of time.

Originally using a simple predator-prey model for HIV production and elimination by the body, Alan showed that the virus had to be replicating at a very fast rate in order for the experiment to show what it did. In order for there to be a balance during the latent period, something had to be eliminating the virus at the same rate. Apparently the immune system was eliminating the HIV virus at an incredibly fast rate. Later experiments measured the HIV level every hour after introduction of a protease inhibitor in order to see the actual rate of HIV elimination, because it was so fast.

The publication of their results led to the realization that during the latent period there was a pitched battle going on between the HIV virus and the immune system. Only when the battle was lost by the immune system did the immune deficiency start. This insight into the dynamics of HIV led to the early treatment of HIV by multidrug therapies which inhibit HIV production. It is difficult to overstate the impact this had on the understanding and treatment of HIV/AIDS and the survival of HIV infected people. It is the main advance in HIV treatment till today, dramatically reducing the rate of death from this disease.

The key idea that Alan Perelson introduced was the importance of studying the dynamic response. This is a central idea in both experimental and theoretical understanding of the behavior of all complex systems.


Ho, D. D., Neumann, A. U., Perelson, A. S., Chen, W., Leonard, J. M. and Markowitz, M. (1995). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123-126.

Perelson, A. S., Neumann, A. U., Markowitz, M., Leonard, J. M. and Ho, D. D. (1996). HIV-1 dynamics in vivo: Virion clearance rate, infected cell lifespan, and viral generation time. Science 271, 1582-1586.

Journal of the American Medical Association HIV/AIDS information center library note.



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