DTC (Imuthiol): Science and Underground

Published in SAN FRANCISCO SENTINEL, April 10, 1987; also published as AIDS TREATMENT NEWS #29, same date.

UPDATE JULY 1987: Important new information from a major French study was released at the III International Conference on AIDS, Washington D.C. June 1-5. See AIDS TREATMENT NEWS #35.


DTC, also called imuthiol, an immune modulator developed in France, has shown encouraging results in early tests for treating persons with AIDS and ARC. Placebo-controlled clinical trials are now running at six U.S. medical centers,
and all these trials are open to accept new patients at this time. (The six U.S. centers are San Francisco General
Hospital, USC and UCLA in southern California, University of Arizona, Institute for Immunologic Disorders in Houston, and Duke University.)

Meanwhile, a few persons with AIDS or ARC have obtained their own DTC, which is a commonly available chemical costing about $40. a pound -- enough for a ten-year supply. Although the highly purified DTC, prepared by the French pharmaceutical company Merieux, Inc., has a near-perfect safety record, there may be other dangers in unsupervised use of the reagent-grade chemical, which was not prepared for human use.


DTC Background

DTC (an abbreviation for diethyldithiocarbamate), has long had various chemical and agricultural uses, and in addition has been used in humans for treating nickel poisoning. It first came to attention as an immune modulator when French scientists, guided by certain chemical properties of DTC, selected it as a candidate for an immune modulator likely to be better than the other ones then available (Renoux and Renoux, 1984).

Yet despite this rational selection process, no one knows for sure how DTC works. It is believed to cause the liver to
produce a substance which causes the growth of T-cells. A laboratory study indicated that DTC may also have activity
against the AIDS virus, and might be helpful for that reason in the early stages of AIDS (Pompidou, Zagury, Gallo and others, 1985), but we know of no published test of antiviral activity of DTC in humans. One French study treated six persons with ARC with DTC, and found clinical improvement in all of them, laboratory improvement in most measures with none getting worse, and no evidence that the increased T-4 counts encouraged growth of the virus (Lang and others, 1985).

The immune modulating action of DTC may start in the brain, causing it to affect the liver and then the T-cells
(Renoux and others, 1984).

Toxicity is low. Animal studies have found that the fatal dose in rodents and dogs is over two hundred times the usual
human dose, adjusted for body weight. Long-term toxicity studies have found that rodents, dogs, and monkeys could tolerate up to twenty times the weekly human dose, every day for three months, without side effects (Renoux and Renoux, 1984). Apparently no one develops allergic reactions to DTC, even if they are allergic to other drugs. There are no known problems in combining DTC with any other AIDS/ARC treatments (but see "Interactions", below). Patients must avoid alcohol for at least 24 hours before and after taking the weekly dose, as DTC is similar to disulfiram (Antabuse), a drug used to help alcoholics stay sober by making them sick if they drink.

DTC may possibly be useful in treating autoimmune conditions. French physicians reported one case of successful
treatment of lupus, a disease known to be autoimmune (Delepine and others, 1985). It is rumored that a number of other people with lupus have also been treated successfully, but we have not been able to confirm this account.


AIDS/ARC Background

Two studies, one in France and one at the University of Arizona but both unpublished so far, have found preliminary
encouraging results.

All this writer knows of the French study at this time is contained in one sentence in the "Clinical Trial Abstract" used
at San Francisco General Hospital: "Initial study in AIDS/ARC showed significant improvement in sx's, decrease in LAS and KS was noted in treated patients compared to the control group." An earlier French study of six ARC patients was described above.

A UPI press release of March 18, 1987 quoted the chief of infectious diseases at the University of Arizona Medical Center concerning the study of 26 patients there. DTC was found to prevent the progression of ARC, although it was not a cure. The researcher suspected that combining DTC with AZT could produce dramatic results, although combined trials will not start until Fall. (Some patients now enrolling in the DTC trial at San Francisco, and probably the other five U.S. centers also, will be allowed to use AZT simultaneously if they want to, now that AZT has been approved and is no longer considered "experimental". But we have heard that only those with AIDS will be allowed to use AZT during the DTC trial -- not those with ARC, even if they meet the Burroughs-Wellcome requirements for obtaining AZT.)

At San Francisco General, physicians Donald Abrams and Robert Gorter are running the DTC trial. Dr. Gorter explained that they decided to join the Arizona study after learning of the preliminary results in France and in Arizona.

I asked how DTC might compare with DNCB, also an immune modulator possibly relevant to the autoimmune component of AIDS. Dr. Gorter had heard that DNCB would raise the number of T-cells in the blood, but that after eight to 12 weeks the number could drop again. With DTC he expected that the effect would last longer, and with much less of a dip.

The San Francisco study will test DTC for six months; 30 patients will get the treatment, 30 will get placebo. Twenty
percent of the patients in each group will be persons with AIDS; the other 80 percent will have ARC. KS is OK if stable,
but persons with MAI are excluded from this test. Blood tests must show HIV antibodies, as well as other indications such as a T-helper count under 500. Because of a Federal rule that patients can only use one experimental drug at a time, patients will not be able to simultaneously use other such treatments.

The French manufacturer of DTC, Merieux, Inc., is financing this study. The U.S. government is not contributing.
Perhaps because of financial constraints, extensive blood tests are being done only at the beginning and the end of the six- month treatment.

At San Francisco General Hospital, places are still open for about 20 more people. Those interested in participating
can call Lillian Kaufman at 821-5531. The other five U.S. centers also have openings at this time.


"Underground" DTC

If all goes well, DTC could be approved sometime in 1988. First, the six different centers must finish recruiting
patients. Then the course of treatment itself lasts six months. Then the data will be analyzed and submitted to the
FDA, which will make its decision. Of course additional delays could occur.

Some people have chosen not to wait and have obtained the chemical DTC. But several problems have slowed the development of a widespread "guerrilla clinic" movement such as the one using DNCB. At this time there is a surge of public interest in DTC, and the problems seem close to being resolved.

DTC is usually taken orally. But the acidity of the stomach would destroy it, so capsules must be "enteric coated",
designed to pass through the stomach and dissolve in the intestines. People have made enteric-coated capsules at home, but the process has been somewhat difficult to learn and do. Fortunately the medicine is taken only once a week. It may be necessary to put the DTC into several capsules so that they will be small enough to enter the intestine undigested.

Besides enteric capsules, other methods are being tried:

(1) People have neutralized the acidity of the stomach so the DTC can get through. This method has been reported to work but it is unpleasant and may be dangerous, as normal stomach acidity may prevent the entry of microorganisms which could be particularly dangerous to someone with immune deficiencies.

(2) In recent weeks, several underground researchers have found that DTC can be administered rectally, in suppositories or by enema. Successful absorption has been inferred from the chemical taste and smell often characteristic of DTC after it has entered the bloodstream. This discovery may make "guerilla clinic" use of DTC feasible.

(3) The drug disulfiram (Antabuse), used to keep alcoholics from drinking, is metabolized in part to DTC inside
the body. Theoretically it might be possible to obtain DTC by taking disulfiram -- a well-understood prescription drug
readily available to physicians. We don't know anyone who has tried doing this yet.

Interactions

Note the warning on alcohol, above.

The Nursing87 Drug Handbook (available for about $20. in medical bookstores) suggest that disulfiram should not be combined with certain other drugs, including isoniazid and flagyl. It is possible that DTC might also interact harmfully
with these drugs.

Underground Notes

The industrial DTC is only rated to be at least 99 percent pure, and at this time we don't know what the impurities are. It is important to find out if there are any dangerous contaminants, and if so how to get them removed. If you can help this research in any way, please call Joe Brewer at Project Inform, at one of the phone numbers listed below.

The FDA will probably ban the sale of DTC once its use for AIDS/ARC becomes well known. We have heard that the FDA already banned the sale last month after a press report of the Arizona results, then lifted the ban in 72 hours when it
appeared that the news would get little publicity; we could not reach anyone in the FDA to confirm or deny this report.
Fortunately DTC is widely used, and quite easy to make in a laboratory; an organized community can easily get around a ban.

Almost nothing is happening with DTC as an AIDS/ARC treatment in any country except France and the U.S. As far as
we know, the pharmaceutical grade is not for sale in any country, although the chemical would remain available abroad
even if U.S. sales are banned. Since the cost of the chemical is negligible, DTC could be particularly important for poor
countries where the cost of other treatments could be prohibitive.

In the U.S., the best way to handle DTC would be to change the rules to allow prescription sale of the
pharmaceutical product. Recently the FDA proposed such a change. If adapted, the new rules will allow limited sale of
drugs for life-threatening conditions, when they are known to be safe and show evidence of being effective, but have not yet achieved final approval. Unfortunately at least one gay political organization has opposed this proposal, apparently fearing that drug companies might abuse it.

This writer believes that any underground use of DTC should follow the lead of the DNCB "guerrilla clinics" in never
charging for the medicine, always giving it free. Free distribution may not change the technical legal status, but politically it makes a guerrilla clinic movement much stronger by removing the issue of profiteering. It also prevents
fraudulent sale of counterfeit, inactive substances.

But note that we should not insist that all alternative treatments be free. AL 721, for example, represents a
different situation, because it costs over a dollar a day to manufacture, and also because it legally qualifies as a food.
It could not be effectively distributed free; but as a nutritional supplement it could be handled by buying clubs or by health-products companies. Many other alternative treatments, such as acupuncture, require professional practitioners. Each situation is different.


For More Information

You may be able to learn more about DTC from Project Inform, (800) 334-7422 from within California, (800) 822-7422
from other states, or (415) 928-0293 from anywhere. You could also try the San Diego AIDS Project, (619) 543-0300. Or call Ron Ringer at (213) 452-2478, or Steve Gavin at (201) 677-2795.


References

Delepine, N., Desbois, J., Taillard F., Allaneau C., Renoux G. Sodium diethyldithiocarbamate inducing long-lasting
remission in case of juvenile systemic lupus erythematosus. The Lancet, November 30, 1985, p. 1246.

Lang, G., Oberling, F., Aleksijevic, A., Falkenrodt, A., Mayer, S. Immunomodulation with diethyldithiocarbamate in
patients with AIDS-related complex. The Lancet, November 9, 1985, p. 1066.

Pompidou, A., Zagury, D., Gallo, R., Sun, D., Thornton, A., Sarin, P. In-vitro inhibition of LAV/HTLV-III Infected
Lymphocytes by Dithiocarb and Inosine Pranobex. The Lancet, December 21/28, 1985, p. 1423.

Renoux, G., Guillaumin, J., Renoux, M. Favorable influences of imuthiol on mouse reproduction and immune system
of offspring. American Journal of Reproductive Immunology and Microbiology, July 1985, p. 101-106.

Renoux, G., and Renoux, M. Diethyldithiocarbamate (DTC); A Biological Augmenting Agent Specific for T Cells. In
Fenishel R. and Chirgis M., editors, Immune Modulation Agents and Their Mechanisms, Marcel Dekker, Inc., New York and Basel, 1984.

Renoux G., Renoux M., Biziere K., Guillaumin J., Bardos P., Degenne D. Involvement of brain neocortex and liver in the regulation of T cells: the mode of action of sodium diethyldithiocarbamate (imuthiol). Immunopharmacology, April
1984, pages 89-100.




********** AL 721 ALERT

Physicians familiar with AL 721 have found four cases of persons who used this treatment and stopped, and developed additional illnesses after stopping.
Two ARC patients in the AL 721 study at St. Luke's/Roosevelt Hospital Center developed AIDS four to six
weeks after discontinuing use of AL 721. In addition, two other persons (not in the study) became less seriously ill, one
with anemia and one with fevers, shortly after stopping.
These cases could be coincidence, due to the progression of untreated ARC. Or they could indicate a "rebound" effect when protection provided by AL 721 is removed. Physicians are recommending that persons not begin AL 721 (including the PC-55 "home formula" or the other substitutes now becoming available) unless they plan to continue the treatment, at least until more is known.




******** URGENT: FDA RULE CHANGE -- PUBLIC COMMENT DEADLINE
APRIL 20

The FDA has proposed a rule change to make it easier for persons with serious or life-threatening conditions to be
treated with investigational new drugs. The change would allow sale of investigational drugs, under rules to prevent
profiteering or premature commercialization. For example, companies could charge for the drugs used in clinical trials
only if the price was not "manifestly unfair", and also if they could show that they had to charge for the drug in order to do
the trial at all. A company could sell an investigational drug for treatment only for serious or life-threatening conditions
when no satisfactory alternative was available, and the company was actively pursuing full approval.
This writer supports the change. It could allow persons with AIDS or related conditions to obtain ribavirin without
going to Mexico. Safe, rational treatments like AL 721 or DTC could be used now; people wouldn't have to wait for months or years, or obtain these medicines underground.
Unfortunately at least one gay lobbying organization has opposed the change, apparently from fear that drug companies could profiteer at the expense of persons with AIDS, while giving them drugs not proven safe and effective.
Written comments can be sent to: Frank E. Young,Commissioner of Food and Drugs, Dockets Management Branch (HFA- 305), Food and Drug Administration, Rm. 4-62, 5600 Fishers Lane, Rockville, MD 20857. Comments must be received by April 20. For more information, you can call Steven H. Unger, Center for Drugs and Biologics, Food and Drug Administration, 301-295- 8049.