HIV is devastating because it attacks and destroys the body’s defense system against pathogens, leaving patients fatally exposed. So what would possess scientists to treat HIV-positive patients with drugs that suppress the immune system?
Such therapy may in fact offer a new approach in the battle against AIDS. An unexpected feature of HIV infection is that in the first few weeks after invasion, the virus hijacks the immune system and sends it into overdrive. Most significantly, the activated T cells—the soldiers that fight germs—not only produce large amounts of cytokines (chemical messengers that help to coordinate a counterattack) but also enter the cell cycle, a process that normally leads to cell division and proliferation. In HIV infection, however, a T cell subtype called the central memory CD4+ T cell appears to enter the cell cycle and undergo apoptosis—cellular suicide—in vast numbers. The activated CD4+ T cell population also helps the virus replicate.
Scientists are not exactly sure how HIV causes the CD4+ T cell population to activate and crash. They do know that the decline is characteristic of HIV infection and use it to make prognoses. They also know that if immune activation is absent, the outlook is very different.
Nowhere is this clearer than in the laboratory with monkeys. The sooty mangabey, found in West Africa, has somehow adapted to the simian immunodeficiency virus—the nonhuman version of HIV—so that even with a high viral load, it rarely gets sick. In contrast, the Asian rhesus macaque will commonly develop a syndrome resembling AIDS. The difference between these two primates is that the sooty mangabey experiences only low levels of immune activation, which presumably limits the T cell population crash and viral replication. In contrast, the rhesus macaque’s immune system, like that of humans, is highly activated in the early stages of infection.
This correlation led researchers to wonder what might happen if the human immune system behaved more like the mangabey’s when confronted by the virus. Experiments have already established that blocking viral replication with antiretroviral medication attenuates immune activation and boosts the number of CD4+ T cells. The next step would be immunosuppressive therapy, which could slow down viral replication by limiting the T cell activation and prevent the CD4+ T cells from committing suicide. “Maybe if we gave antiviral medications and blocked the downstream pathways that are driving T cell turnover, we might be able to enhance CD4+ T cell restoration and T cell function,” says Michael Lederman, director of the Center for AIDS Research at Case Western Reserve University.
Several teams around the world have been investigating this unusual approach, with mixed results. Lederman and his colleagues conducted trials in 2001 and 2003 of the corticosteroid prednisone in conjunction with antiretroviral therapy. The therapy succeeded in blocking immune activation but failed to affect CD4+ T cell populations.
A European team fared better with cyclosporine A. In a nine-patient trial—and later, in a study of nearly 80 patients—CD4+ T cell counts rose to normal levels after eight weeks of cyclosporine A and antiretroviral therapy, says immunologist Giuseppe Pantaleo of the University of Lausanne in Switzerland, a key investigator in the trials. “We were indeed surprised by the magnitude of the effect on the CD4+ T cells,” he remarks.
Pantaleo’s results stand in stark contrast to some previous attempts. In 1989 Canadian researchers attempted to treat patients with AIDS using cyclosporine, with unfortunate consequences. Not only did patients experience severe toxic symptoms from the treatment, but their T cell counts plummeted.
Hence, timing seems to be important with this kind of HIV therapy. “This is not, in my mind, an approach to take during chronic infection, because once infection has been established, the mechanisms of immune activation become much more complicated,” observes Martin Markowitz, staff investigator at the Aaron Diamond AIDS Research Center in New York City. “I don’t think that you want to intervene in a disease that is characterized by progressive immunosuppression with immunosuppression.”
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2 Comments
Add CommentI am afraid that these researchers have a conflict of interest. It is called having a job or being employed. The fact use of Prednisolone is now almost standard among many feline that have FIV. One book "Pets at Risk" uses it for FIV.
Reply | Report Abuse | Link to thisBut I do not use it and instead use licorice root something that the Japanese use but has the effect of suppressing HIV virus. And HIV trial lastest for 11 years success in its use.
I am afraid that the great fear is that drug companies will lose billions of dollars if their drugs are replaced and like every business tries to stop competition. This shows a problem with what goes on in the field of medicine when it should be concerned with saving lives instead of making money. NO don't this is getting off the subject of immunosuppression. But bias is a fact of life which is why alot of research is nothing more than nonsense in the hope of misleading. And not a search for truth.
On the subject of immunosuppression you do not quote two important studies which show differnet results. One from France and the other from Germany. The other is patent 5,846,961 by Knox Van Dyke "Multi-Facted Method to repress reproduction of latent viruses in humans and animals file June 7, 1995. It mostly has FIV but onlye one HIV trial.
The use of Prednisolone for HIV should be 5mg as what it really is doing is anti-inflammation more than suppression. But it does deal with overactation of HIV. In SIV which does not advance to AIDS the monkey immune system tolerates the virus instead of attacking it. The use of prednisolone is a method of trying to do something similar. The failure of researchers that you have shown is simply they had no idea what they were trying to do and likely were not motivated to successed for reasons I have stated. You really have to be motivated and not be concerned about money, career and all the other things causing failure
I myself have a FIV infected cat named tiger that I treat and has the FIV infection for ten years. He is in good health and likely to live many more years. I was the first to use three HIV drugs to treat FIV but these drugs have problems both in HIV and FIV. Instead I use supplements and herbs which are not very toxic and do not have HIV drug problem. Besides the cost is low. Recently, 18 month HIV trial of Immu-25 from India showed good results. Still what we get from press and government is silence. This also goes for Nobuto Yamamoto work on Gc-MAF. Anything that would effect money making from major drugs companies seems to produce silence even cures.
Reply | Report Abuse | Link to thisBook "Pet at Risk" shows the use of Prednisolone. Patent 5,846,961 by Knox Van Dyke also shows use of this drug for both FIV and HIV. Andrieu in France successful used if for HIV around 1993 for suppressing immune system.