After becoming HIV positive, most people usually remain physically well for years. During this time, despite outward appearances, HIV is constantly attacking the immune system. As the damage from HIV builds up, levels of important immune cells called CD4 cells gradually decline. Eventually the body is unable to repair the damaged immune system, leading to an AIDS diagnosis. This decline in the immune system is called disease progression.

It is noteworthy that a small proportion of people have a very different response to HIV -- one that is found in only about 1% of HIV-positive people. Researchers have found that this minority has relatively high and stable CD4 cells, low amounts of HIV in the blood, and no symptoms of HIV-related disease for prolonged periods. These people are not taking anti-HIV therapy and are called long-term non-progressors (LTNPs).

There may be several reasons that some people with HIV become LTNPs. Some are simply lucky to be born with immune cells that are difficult for HIV to enter and infect. Others may be infected with a relatively weak form of HIV. Yet research is accumulating that suggests that a vigorous immune response against HIV may play a role in helping to keep LTNPs healthy. If this immune response could be understood, perhaps better therapies against HIV could be developed.

A Possible Culprit

Researchers in North America and Western Europe have been studying the way the immune systems of LTNPs and other people with HIV respond to the virus. Several teams have begun to focus on a chemical signal -- or cytokine -- produced by the immune system called interleukin-10 (IL-10).

In one series of experiments, researchers in Toronto have been assessing the level of IL-10 producing cells in different groups of people. As reported in the Journal of Infectious Diseases in November, they found that the levels were greatest in HIV-positive people whose CD4 cell counts were declining and/or whose viral loads were relatively high. The group with the second greatest amount of IL-10 producing cells was made up of people who were newly HIV positive, and LTNPs made up the group with the lowest levels. Indeed their levels were almost as low as those of HIV-negative people.

As always seems to be the case with HIV, different research supports different theories. Older studies have suggested that IL-10 injections could reduce the ability of HIV to replicate, both in vitro (in the test tube), and in people. In fact, daily IL-10 injections have been studied in clinical trials, the theory being that IL-10 may inhibit viral replication by controlling other cytokines and enhancing "killer" T-cells. Unfortunately, these studies showed no benefit for people with HIV/AIDS.

Why Should IL-10 Levels Matter?

The immune system uses IL-10 to help suppress inflammation and prevent immune responses from getting out of control. In other words, once invading bacteria, fungi, parasites or viruses have been suppressed, the immune system uses IL-10 to shut down responses that are no longer needed and that could be harmful. But too much IL-10 is not a good thing. In infections such as tuberculosis and toxoplasmosis, over-production of IL-10 appears to allow these infections to persist. Interestingly, proteins produced by HIV cause the immune system to respond by producing IL-10. It seems, therefore, that in some people with HIV, the balance between fighting an infection and suppressing immune responses against that infection is lost in favor of weakening the immune response.

What Can Be Done?

Use of highly active antiretroviral therapy (HAART) is able to reduce the level of IL-10 producing cells in some but not all people with HIV/AIDS. To go beyond this, perhaps a different approach is needed. In November, the Journal of Experimental Medicine reported on research conducted at the National Institutes of Health. Mice with a severe and persistent parasitic infection were given antibodies that blocked the effect of IL-10. The researchers found that blocking IL-10's effect helped the animals overcome their infection.

By extension, it's possible that this form of anti-cytokine therapy could have an impact in people with HIV/AIDS. But this idea needs to be tested in monkeys with simian immunodeficiency virus for at least two reasons: first, to explore its potential efficacy; and second, to highlight any toxicities that might occur if it's tested in people. It may be possible that regular doses of anti-IL-10 could help shift the immune system to a state resembling that of long-term non-progressors.

Sean R Hosein is the Science and Medicine Editor at the Canadian AIDS Treatment Information Exchange (CATIE).