Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
The Bay Area Reporter - Friday, January 24, 1999
Jeff Klausner and Larry Hanbrook, ACT UP/Golden Gate Writers Pool
Researchers have shown that HIV infection causes chronic immune activation. This means that people have increased levels of activated or "turned on" T cells in the blood, increased number of cells programmed to die, increased levels of cytokines (chemical messengers between cells) and decreased responsiveness of the immune system. In fact, HIV-positive people frequently exhibit typical clinical signs of chronic immune activation: low energy, weight loss, fevers, poor appetite, swollen glands, and poor immune responses to common environmental agents (anergy). This immune over-activation undermines the immune system's ability to respond to infections.
Rejection protection
If HIV causes AIDS by chronic immune activation, then treating HIV infected individuals with an inhibitor of immune activation might block the underlying disease process. One novel approach to treating HIV infection is - rather than to target the virus directly - to reduce the over-activation of T cells. One of the oldest and best studied drugs that blocks activation of T cells is cyclosporine.
Cyclosporine is an agent widely used to suppress the immune system, and is used primarily during organ transplantation and as a treatment for psoriasis. When a person receives an organ from someone else, the natural response of the body is to reject that organ. Cyclosporine blocks the rejection by preventing immune activation and T-cell proliferation.
Several studies have described cyclosporine use in patients with HIV infection. Published studies have suggested that cyclosporine is safe in HIV-positive persons without AIDS. HIV-positive persons without AIDS have received cyclosporine without an increase in harmful effects and have had some benefit. A French study in 1991 demonstrated that cyclosporine-treated HIV-positive patients had improvement in symptoms, increases in CD4 cells and a slower progression to AIDS when compared to untreated controls. A German study in 1993 showed that HIV-positive patients without AIDS who received cyclosporine during kidney transplantation progressed to AIDS slower than HIV-positive patients who did not receive cyclosporine.
However, not all HIV-positive persons who have received cyclosporine have done well - as was shown in a Canadian study in 1989 and in the French studies. In one study, AIDS patients had worsening of symptoms and decreases in CD4 cells. In another study, patients with CD4 cells less than 300 did not have substantial improvements in CD4 counts or resolution of symptoms. These negative results in HIV-positive persons with AIDS led to a cessation of research with cyclosporine.
More recent studies in the U.S. have shown that cyclosporine can influence primary SIV (simian immunodeficiency virus) infection in animals and may actually increase dormant immune responses. As well, cyclosporine may also have direct antiviral effects by blocking the binding of HIV to its cellular receptor, as some in vitro studies seem to show. Drug companies are currently exploring the antiviral effects of cyclosporine. Clearly, further research in the use of cyclosporine in treating HIV infection is warranted.
Transplants
Aside from a being a potentially new treatment for HIV, cyclosporine, as noted, is frequently used during organ transplants. HIV-positive patients, just like anyone else, have the right to receive organ transplants. But one of the key problems is that patients who receive organ transplants must go on therapy that prevents rejection and use drugs like cyclosporine. The medical and insurance communities are reluctant to offer organ transplants to HIV-positive patients until they know that drugs like cyclosporine are absolutely safe.
Community participation in these studies is very important, not only to understand how HIV causes AIDS but also to advance the rights of HIV-positive persons for organ transplantation. t
ACTion UPdate:
There are two studies currently enrolling patients in San Francisco using cyclosporine to treat immune activation in HIV-positive individuals who are and who are not on antiviral therapy. One study is at San Francisco General Hospital (ACTG 334, please call (415) 476-4082, x360) the other study is at a private research center, Virx (please call Debbie Hildebrandt at (415) 474-4440).
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