The Bay Area Reporter - July 16, 1996
Rob Sabados, ACT UP/Golden Gate Writers Pool

Who will get lymphoma?

Researchers are developing a potential blood test that may allow physicians to predict which patients are likely to develop lymphoma in the next 12 to 18 months (Abstract Mo.B.431). AIDS-lymphoma, a condition that affects three to ten percent of people with AIDS, remains an often terminal condition. One significant difficulty in the treatment of AIDS lymphoma is that patients frequently find out too late that they have lymphoma. Diagnosis can be delayed as lymphoma symptoms such as fevers, swollen lymph nodes and weight loss can be mistaken for symptoms of HIV or other opportunistic infections. As a result, treatment can be more difficult, and sometimes futile.

Researchers at the Multicenter AIDS cohort study site in Las Angeles compared blood collected from people later diagnosed with AIDS lymphoma with that of people with HIV and AIDS as well as with HIV-negative persons. They found that levels of blood levels of sCD23, also called B-cell growth factor, were twenty times higher in patients who developed lymphoma in the next 12-18 months compared with all other groups. They also found that significantly elevated levels of IgE (a class of antibodies linked to allergic reactions) and sCD27 (a molecule has a stimulatory effect on the immune system). This may also explain how lymphomas occur since most AIDS-lymphomas are caused by an over-proliferation of B-cells.

Researchers concluded that "significantly elevated levels of sCD23, IgE, and sCD27 were seen in those who developed AIDS lymphoma, when compared with others with AIDS (without lymphoma), or to HIV- or HIV+ subjects who did not have AIDS." In an earlier article (Blood, 85(7):1843-9), these researchers discuss sCD23 and IgE in more detail.

These tests may make it possible for physicians to determine which patients are at high risk for developing AIDS lymphoma, much as markers such as beta-HCG and alpha-fetoprotein are currently used to track possible tumors. Physicians and patients will then be able to watch for, and more aggressively evaluate, possible lymphoma symptoms.

In the future, it may be possible to prevent lymphoma by treating patients with elevated levels of these compounds with immune-modulators or antiviral agents that target HIV or lymphoma-linked viruses such as Epstein-Barr virus.

Interestingly, it is possible to get IgE measurements through many medical laboratories, including the clinical lab at San Francisco General Hospital. Similarly, kits to measure sCD23 levels are available from Cambridge, Massachusetts-based T-Cell Diagnostics, raising the possibility that interested commercial and hospital laboratories could provide this test to patients.

These tests are not approved for this purpose, however, which raises difficulties in reimbursement and interpretation of results.

Safer sex through chemistry?

In addition to reducing HIV viral load, antiviral therapy may also lower the amount of HIV in semen, thereby reducing the risk of transmission. One study (Mo.A.1083) found that use of reverse transcriptase inhibitors such as AZT, ddI, and delavirdine resulted in a 16-fold reduction in the amount of HIV RNA in semen. No HIV could be detected in the semen of two-thirds of the 15 patients studied.

Another study (We.C.334) found that the semen of patients not on anti-viral therapy was 4.1 times more likely to contain HIV RNA than those on combination therapy. It is important to note that the inability to detect HIV in the blood does not guarantee the absence of HIV from semen. While not a substitute for safer sex practices, effective anti-viral therapy may help reduce the risk of HIV-transmission.

Among women, use of birth-control pills (Tu.C.2965,We.C.333) and the presence of sexually transmitted diseases (numerous, including We.C.332 and We.C.333) led to increased amounts of HIV in cervical and vaginal secretions. These findings underscore the need for timely treatment of sexually transmitted diseases, as well as for further studies of the role of oral contraceptives in HIV-transmission.

A new class of protease inhibitors

During the conference, Pharmacia & Upjohn introduced a new class of protease inhibitors called dihydropyrones (die-hi-dro-pie-wrowns). These drugs were designed using computer modeling techniques to optimize their activity against the virus, an approach known as rational drug design. Structurally different from the other protease inhibitors, dihydropyrones are highly active against HIV, including viral strains that have developed resistance to other protease inhibitors. This provides a important option for patients who have failed or needed to stop taking the other protease inhibitors.

Based upon animal and in vitro studies of safety, anti-viral potency and absorption, Pharmacia & Upjohn has selected one compound, U-140690, for further study. The company hopes to begin human studies in January 1997.

Vaccine update

The Vancouver conference also addressed another important and often neglected area of AIDS research: the development of a safe and effective vaccine to prevent HIV-infection. Such a vaccine is the most effective way to end the nightmare that has decimated communities around the world. "People have begun to recognize that vaccines need to be a high priority since 90 percent of People with AIDS will never have access to the drugs that have been developed," commented ACT UP/Golden Gate member Bill Snow.

At the conference, Office of AIDS Research (OAR) director and former immunology researcher Dr. Bill Paul gave a Distinguished Lecturer speech in which he criticized researchers for still using 50-year-old science instead of the state-of-the-art vaccine technology that now exists. Prior to becoming director of the OAR, Dr. Paul proposed that researchers use cytokines (regulatory proteins produced by the immune system) to enhance vaccines. These vaccines would work with the immune system in a far more sophisticated manner than the vaccines that currently exist.

Considerable attention was also paid to possible trials of the DNA and "naked-DNA" vaccines being developed by Merck. These vaccines contain DNA fragments that enter the recipient's cells, causing them to begin producing a viral or bacterial protein. The body then produces an immune response against that protein, a response that should provide longterm protection. Some researchers, however, are concerned about the longterm effects of injecting patients with foreign DNA.

In the United States, the Pasteur-Merieux/Chiron vaccine that uses a technique called "prime and boost" has progressed rapidly to Phase II studies. This vaccine uses two parts: a viral vector (another virus that contains pieces of HIV) to prime the immune system for the second part, a sub-unit (part of the HIV-virus) to boost the immune response.

During the conference, researchers debated whether to test currently available vaccines in the third world as current vaccines fail to protect a significant fraction of persons receiving them. Dr. John P. Moore of the Aaron Diamond AIDS Research Center in New York City argued that more basic research should be conducted prior to testing vaccines, while Dr. Edward K. Mbidde of Uganda argued that the need for a vaccine in the third world is so intense that we need to move ahead with vaccines that protect even a fraction of those who receive it.

In order to expedite research and to ensure a globally-coordinated effort, the New York-based Rockefeller Foundation has developed the International AIDS Vaccine Initiative to coordinate research and funding. For more information, contact the International AIDS Vaccine Initiative; c/o Rockefeller Foundation; 420 Fifth Ave; New York NY 10018 or send a fax to (212)784-3468.

ACTion UPdate:

An open letter from ACT UP/Golden Gate

The members of ACT UP/Golden Gate would like to thank the gay, lesbian, and AIDS communities for making possible our attendance at the XI International AIDS Conference in Vancouver. As an all-volunteer non-profit group that accepts no pharmaceutical company money, we are entirely dependent on community donations and T-shirt sales. Your continued generosity makes possible our work on behalf of people with HIV and AIDS.

We would like to specifically thank the many individual donors as well as the San Francisco AIDS Foundation, Mobilization Against AIDS, and Re-Juice-A-Nation for their financial support.

In the coming weeks, we will report on our activities, experiences, and what we learned while in Vancouver and how they will benefit people with HIV and AIDS. To learn more, please read our weekly writer's pool columns or attend our Treatment Issues Committee meetings. These meetings are held every Tuesday night at 592-B Castro at 7:30 p.m. and are open to the public.

Sincerely,

The members of ACT UP/Golden Gate

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