Gay Men's Health Crisis: Treatment Issues, Volume 8 no. 4 - June 1994
Dave Gilden and David Gold

In 1992, the National Institute of Allergy and Infectious Diseases (NIAID) reviewed thirteen different LDAI studies here and abroad. The Institute concluded, "The initial claims which have been made on behalf of Kemron ... have not been confirmed.... People with HIV infection will be best served if they receive treatments which have been shown efficacious in well controlled studies."[1]

At the 1993 International Conference on AIDS, Elly Katabira, M.D., of Uganda announced the results of a 560-person placebo-controlled trial.[2] The study, which was sponsored by the World Health Organization, found no difference between Kemron and the placebo. There was no evidence of any effect on CD4 cells, viral load, disease progression, survival or "quality-of-life" indicators.

Nevertheless, officials at NIAID, the division of the National Institutes of Health (NIH) that receives almost half of all U.S. government AIDS research dollars, are proceeding with plans for another large oral alpha interferon trial. Taking the lead in planning and funding the study is the Community Programs for Clinical Research on AIDS (CPCRA), a unit of NIAID.

Why Another Trial?

Even those planning the study do not believe that oral alpha interferon works. Dr. Lawrence Deyton, Director of the CPCRA, readily admits that "scientific evidence proves [the LDAI] products give no benefit in fighting HIV or in improving the immune system of persons with HIV infection."[3] Why then proceed with an expensive new test that only prolongs uncertainty over the substance? Dr. Deyton argues that continued community use of LDAI, particularly in the African- American community, requires yet more definitive testing of the substance.

Why not just publicize the results of the WHO/Ugandan study then? "We accept the immunological and virological data from the WHO/Ugandan study," Deyton told Treatment Issues, "but the quality of life issues are clouded. The Ugandan people were very sick to start with." Additionally, deficient care may have obscured the results. The new LDAI trial will primarily investigate whether the therapy causes any reduction in clinical symptoms related to the HIV-associated decline in immunity.

Small trials in Los Angeles and New York did find some slight symptomatic relief, mainly in terms of restored energy and weight. But with enough studies, some positive data will always appear, just from random variation. These results are specifically countered not by just the WHO/Ugandan study, but by a trial conducted through the Community Research Initiative of Toronto in 149 HIV-positive individuals,[4] in addition to all the other oral alpha interferon studies that found no significant effect from the drug.

Most researchers do not believe that oral alpha interferon can have any effect because the interferon protein is broken down and rendered useless by fluids in the stomach. That is why all interferons approved for therapeutic use are injected subcutaneously (into the skin). The conjecture that alpha interferon directly affects immune cells in the mouth and sparks an improvement in immune system responsiveness remains highly speculative with no supporting data.

Wasting Precious Dollars and Goodwill

The new trial, which will enroll 800 people and compare three versions of LDAI, is to begin later this year. The cost of the study may be in the millions (not including the cost of NIAID staff time in planning and overseeing the trial). Dr. Deyton claims the cost will be less, but refused to be quoted on a specific figure.

In addition, the smaller and more difficult a drug's benefit is to measure, the larger and more extensive a clinical trial must be to document that benefit. There is no reasonable assurance that this trial will prove large enough to show any quality-of-life benefits from the drug. Failure of this trial to document an effect from LDAI may only elicit calls for another, still larger trial.

Besides consuming valuable research funds and staff time, the proposed trial will waste human resources. People who enroll in a clinical trial are contributing the most valuable thing they have - their bodies. It is unconscionable to enroll people in a clinical trial, particularly one sponsored by the U.S. government, when there is no reasonable evidence that the therapy being tested is of benefit. Individuals participating in this study may forego other therapeutic options, or render themselves ineligible for more appropriate clinical trials. They also may become further disenchanted with the clinical trial system when the false hopes played upon to draw them into the trial are dashed.

Rather than improve relations between the scientific and African-American communities through this trial, as has been hoped, the gap between the two may only grow more insurmountable.

Making Sense of Research Priorities

Many observers, including The New York Times, report that LDAI is being kept alive by political pressure, especially from medical clinics connected with the Nation of Islam, which has helped popularize LDAI in the African-American community.[5] But LDAI has also received support from the National Medical Association, the well-established organization of African-American physicians in the United States.

The chair of the LDAI protocol team, Lawrence Brown, M.D., of Brooklyn argues, "Things are not driven by pure science, there's politics on all sides: Who believes in what data? Look at all the effort put into AZT, and with such little yield."

Dr. Brown is exactly right. Too much government funding has gone towards studying AZT and its sister drugs, ddI and ddC (although these drugs at least can reduce viral load and provide modest increases in CD4 levels - oral alpha interferon does neither). Let's not do the same with LDAI, while leaving promising experimental therapies and areas of basic virological and immunological research starved for funds. LDAI keeps reappearing precisely because the medical establishment has nothing really effective to offer people with HIV - especially those in disenfranchised and poor communities, who have the least access to care and promising therapies.

The LDAI saga sums up much of what is wrong at NIAID: endless trials of mediocre drugs without any clear insight into what strategies could yield effective therapies and an all too pervasive acceptance of wasteful and redundant clinical studies. Let people take Kemron - if they want it. NIAID resources should be used for more productive lines of research.

This is the first in a series of commentaries that will appear in Treatment Issues on AIDS research at the NIH.

References:

1. National Institutes of Health. Interim Report: Low-dose oral interferon alpha as a therapy for human immunodeficiency virus infection (HIV-1): completed and on-going clinical trials. April 1992.

2. Katabira E, et al. IX International Conference on AIDS, 1993; abstract PO-B26-2056.

3. Deyton L. Letter to CPCRA Steering Committee. October 5, 1993.

4. Hulton, MR et al. Journal of Acquired Immune Deficiency Syndromes, 1992; 5(11):1084-90.

5. The New York Times. March 4, 1994.

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