Being Alive Newsletter, Being Alive/Los Angeles - June 1992

Attendance at the working conference was by invitation only. To facilitate free exchange of ideas, there was an agreement to have no press, no direct quotations, and no release of specific data. To make the gist of the information available to the community, Project Inform's Martin Delaney gave a a long interview to John James, featured in the May 15, 1992 issue of AIDS Treatment News. If this summary and excerpts interest you, we certainly urge you to read the full interview at the Being Alive or another AIDS library or by requesting the issue from ATN.

BACKGROUND

Martin Delaney notes that two years ago, "Project Inform made an internal decision to direct its research efforts toward late-stage disease and restoration of immunity ... not out of any disbelief in the virus, but because everybody else was working on that, and there wasn't enough attention given to immune restoration. ... Over time everybody with the disease must confront the problem of the damage done to the immune system."

At PI's urging, the Institute of Medicine hosted a state-of-the-art review conference on immune restoration in December of 1990. From this and a subsequent meeting on disease pathogenesis [the process by which the immune system is damaged and HIV-related diseases occur], PI realized that the people in this field weren't talking to each other [as has too often happened throughout the epidemic]. PI decided that it must continue the process itself, with informal meetings guided by experienced facilitators who could help the group formulate the next stage of the research agenda as well as specific projects.

The conference was exciting for many reasons, among them that a relatively small group of top AIDS researchers met for two days of rare cooperative sharing and cross-stimulation of ongoing research, that it was convened by an activist/advocacy group, that it focused on immune system preservation and restoration, that the potential for helping people at the very late stages of disease was highlighted.

As Delaney observed, "Some of the researchers there said this was the first time in their ten years of working with AIDS that anybody had asked them to focus on the very late stage of the disease. They also admitted that the scientists and the government people had always been operating under the assumption that these people are written off. We've always suspected that; this is the first time I have heard them own up to it.

"But having said that, they then said, `That's an interesting challenge. Why is it all that different, say, from bringing somebody back after a bone-marrow transplant with cancer? It's not something that inherently dictates abandoning the patient.' It was a new thinking process for them, to begin looking at it in that way. ...[A] general consensus ... evolved among them ... that when people had gone down to the 50 or 100 T-helper cell levels, there was far more resilience in the immune system than any of them would have anticipated just a couple of years ago."

RESEARCH AREAS

Top researchers in different areas of immunology were invited; nearly everyone invited arranged to attend. The assembled scientists represented the cutting edge of research in the following areas:

Cell line expansion, including cryopreservation. This involves taking particularly CD8 or T-suppressor cells from a patient's body (perhaps freezing them for use later on at a more advanced stage) and cloning them or multiplying them outside the body before infusing them back in. "It is widely believed that these cells produce an unknown soluble factor which inhibits HIV. CD8 cells also appear to inhibit KS." These expansion techniques are new, having only been tested in a few people, but "got nothing but respect from the group....There was some discussion about whether to expand all the CD8 cells [or whether to expand] only the CD8 cells which make the antiviral factor, [i.e.] the...killer cells which will kill HIV-infected cells. At least the activists in the room thought there might be a problem with the selective approach, because it banks everything on combating HIV whereas the principal benefit seen from CD8 expansion so far was an anti-KS effect, which probably was not mediated through HIV. So wouldn't you want to expand all the CD8 cells ? There might also be cells specific to other diseases. The evidence was that there was no harm from expanding all the cells."

Gene therapy (using a vector to add new genes to cells in the body, such as T-helper cells, to make them immune to HIV, or for other purposes) and stem-cell research (the stimulation of embryonic cells in the bone marrow which can grow into many different kinds of immune system cells). "In gene therapy, we were struck by how far along it is farther than most people believe. Some of the groups at the meeting claimed to have something virtually ready for human testing; but they are nervous about the regulatory and policy obstacles. ... We will get behind them on this, and see if some regulatory pressure could be released, so they could start testing. ...Another US researcher was urging the opposite approach to go slow, for fear of a backlash if something went wrong from a premature experiment. ...We talked about willingness to take risks in the research process, and go forward. Some of them agreed, and even thought it was important that they be reminded of that regularly." [See also Being Alive Newsletter article, March 1991.]

The activists stimulated the researchers to think of combining gene therapy and stem cell research. "We pointed out that gene therapy efforts so far seemed to be devoted to one thing: producing an antiviral response inside the cell. We asked why not also use gene therapy to stimulate cell-line growth. The answer was, `Yes, we could do that.'"

Passive immunotherapy [see Mark Katz's Medical Update in this issue]. "We contacted the Veterans Administration in New York, which has conducted a small trial infusion of plasma which is rich in anti-HIV antibodies. They came to the meeting, but chose to talk about monoclonal antibodies instead, feeling that was more hopeful than the plasma-transfusion approach."

Soluble factors (proteins such as IL-2, alpha interferon, TNF or tumor necrosis factor, thymic humoral factor or THF which are found in the blood and which may have either helpful or harmful effects on disease progression). "...We had presentations from Italy on the thymosin study, from France on THF, and on IL-2. The IL-2 is probably the most thoroughly developed data, most intensively studied; it showed no evidence of boosting viral levels, as had been feared since it stimulates the growth of T-helper cells, some of which are infected. The drug produces a `sawtooth' effect, with T-cell counts rising rapidly after infusion of IL-2, then dropping again with time after the infusion. But over time, the trend remained above baseline....IL-2 alone is not the answer, but it may be a part of it....What is interesting about the soluble factors is that all are showing some activity. Then why not try them together? None alone is enough by itself."

Transplants. "There was also a review of the bone-marrow transplant data. That was a history of disappointment. For awhile the treatment seemed to show benefit; but then the growing cell counts would hit a wall and collapse, usually within a year. The researchers' explanation was that this must be happening because virus is still there. We suggested that the problem might be due to other factors suppressing cell growth, factors we haven't identified yet."

Therapeutic vaccines. "The roundup on the vaccine area was the commitment to consider therapeutic vaccines for persons with lower T-cells, and to combine the vaccines with soluble factors or antiviral medications. We will meet with the US experts to try to develop protocols. In Europe, the problem is funding, as well as scientific rivalries."

We applaud Project Inform and Jesse Dobson for their leadership and diligence in forging this type of collaborative arena to move HIV/AIDS research forward. The focus on giving realistic hope to those even in the advanced stages of disease, on rebuilding immune systems beyond the first goal of halting the damage, is overdue among top researchers and could prove historic. The discussions among key scientists working in different but related areas, focused by questions from skillful PWAs and advocates, immediately yielded promising ideas for fruitful collaboration. We need much more of this.

(Excerpted and summarized by Walt Senterfitt, based on John James, "Immune Restoration Conference: Interview with Martin Delaney, Project Inform," AIDS Treatment News, No. 151, May 15, 1992. P.O. Box 411256, San Francisco, CA 94141. 415.255.0588.)
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