The Bay Area Reporter - July 14, 1998
David Mahon, ACT UP/Golden Gate Writers Pool
The experiment was the idea of the researchers, led by Mike McCune, M.D., Ph.D. at the Gladstone Institute of Virology and Immunology at San Francisco General Hospital (SFGH). These researchers have been looking at the functioning of the thymus in people with HIV. The thymus is the organ in your body that stimulates undifferentiated immune cells to become T-cells. It is situated behind your sternum (or breast bone). It was traditionally thought that the thymus was a fully functioning organ only in children, that when people became adults the thymus shrank and didn't have any more use.
The researchers at the Gladstone Institute have been using CT scans to try to visualize thymus tissue in HIV-negative and HIV-positive adults. They have found that there is indeed functional thymus tissue in adults and that interestingly enough, many HIV-positive people had a larger thymus than corresponding HIV-negative controls of the same age. The findings from this study were published in the June 1998 Journal of Clinical Investigation (Vol. 101, No. 11). These findings led the researchers to believe that the thymus was still able to play an active roll in creating more T-cells in adults, especially in T-cell-depleted HIVers.
This is exciting news, as triple combination therapies are able to kill off most of the old infected T-cells, the thymus was able to regenerate a new batch of T-cells. This would leave the body with mostly new uninfected T-cells. One problem existed in that there always seemed to be a reservoir of infected T-cells that were hidden away in the lymph nodes, that only "came out" when they were stimulated by a particular antigen presentation. When these T-cells became stimulated they multiplied, spreading HIV infection into these new cells, which could then go forth and infect any other newly created T-cells.
This problem of a reservoir of latent HIV-infected cells has concerned scientists since the theory of an HIV "cure" was first postulated by David Ho two years ago. Dr. McCune and his associates at the Gladstone were interested in this problem and came up with an idea to specifically attack this reservoir of sequestered HIV-infected cells. They were familiar with the work of Dr. Steven Deeks, a colleague at SFGH, who had performed the famous baboon bone marrow transplant on AIDS activist Jeff Getty in 1995. Before Jeff had received the transplant, Deeks had used radiation to make room in his long bones for the new bone marrow and to suppress his lymphocytes (white blood cells) so that they would not attack the foreign bone marrow. As it turned out, the baboon bone marrow did not have any effect on Getty's immune system. But another surprising result did occur. After years of next-to-no T-cells, Getty's T-cell numbers moved up to 100 and above. His viral load had been detectable before the radiation, but became undetectable within weeks following the radiation. All this was happening with no change in his drug therapy.
The explanation for this seemed to be in the radiation treatment. His infected T-cells may have been killed off and afterwards new T-cells were regenerated that were not infected. Using the newly available combination therapies, Getty was able to suppress infected T-cells from proliferating and infecting these new T-cells. The folks at the Gladstone Institute, who had a pool of HIVers whom they had thymus data on, wanted to directly evaluate the possibility that radiation might indeed kill off infected T-cells and permit new T-cell production from the thymus.
I was in their thymus study and volunteered to be one of the candidates for radiation. I was chosen last summer because I was on stable triple combination therapy and also because my thymic size and function had been previously studied. They planned to experiment with 3 different doses of radiation: 450 rads (a dose similar to the one which Jeff had received), 300 rads and 150 rads. For comparison, someone with cancer might receive 3,000 rads total during their treatment. The researchers wanted to use only the lowest dose (150 rads) on me as they wanted to make sure that the experiment would not be harmful in any way. They explained to me that there was little likelihood of harm, but also because they were using such a small amount of radiation, there would also likely be little benefit.
I figured, since I'd already lost my hair due to family genetics, what did I have to lose besides infected T-cells? So I underwent a battery of examinations. I was all set to go, when the radiologist stopped the proceedings as she said I was "too healthy." On the triple combination therapy for over a year, my viral load was below 500 and my T-cells were continuing to rise from the low 100s into the 400s. She explained that we wouldn't be able to determine if any subsequent increase in T-cells would be due to the radiation or the drug therapy. So my entry into the study was put on hold.
I was approached again about the experiment this past spring. My T-cells had stabilized in the low 400s over the past half year, while my viral load remained below 500, so any dramatic change could be better related to the radiation treatment. They zapped me with the radiation April 21 in a most protective environment: they had devised a way to shield my thymus, my long bones with their bone marrow tissue, and my other vital organs from the radiation. The process took about an hour, where I had to lie as still as possible. The radiologists were extremely careful to radiate only the desired lymph tissue. Afterwards I spent an overnight at SFGH for observation. They had given me an anti-nausea medication the day of the radiation and I felt no side effects either right after or since the treatment.
My first blood test following the treatment revealed that my helper T-cells had dropped into the low 200s. McCune and his associates expressed surprise that the small amount of radiation to my lymph nodes had effectively destroyed so many T-cells. My T-cells remained in the low 200s for about a month. In the first two months after the radiation treatment my T-cells leveled off in the mid-300s. I go in for blood work monthly and will be monitored for a year. I have nothing but good things to say about everyone involved in this project, each of them was personally caring and concerned for my welfare all the way through the project. I was told that I could back out of the study if I had any concerns, even up to the last minute. The staff and researchers were always ready to address any questions or concerns that I might experience throughout the whole process.
With the initial success of my experiment, McCune is looking to evaluate this treatment on a few other PWAs. They have a list of potential recipients, but are also looking for others who are interested in this study.
Anyone who is interested in finding out more about this experiment or others trials that are being done at the Gladstone Institute is invited to call Diane Schmidt at (415) 695-3820.
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