The Washington D.C. AIDS Conference: Part II (Part two of three parts)

Part I of this article (AIDS Treatment News, #34 June 19) cited the new optimism among scientists and physicians about the possibility of developing treatments for AIDS and ARC. The leading experts are now moving from seeing AIDS as a certain death sentence, to considering the possibility that it may become like diabetes -- usually controllable with continuing treatments, although still without a cure in sight.

The treatments which eventually will make HIV controllable probably exist now. But only the Federal government has the resources to move quickly and get testing underway for a wide range of plausible treatment options. Unfortunately, except for a handful of commercially attractive possibilities (mainly AZT), U.S. public policy has simply not included a serious effort to save lives through treatment development. So today dozens of treatments which could have been tested long ago are seeping out through the cracks of the system, often supported by tiny groups of researchers without the resources to make headway against a government and commercial structure so complicated, expensive, and ingrown that it systematically shuts out all but the best financed and best connected.

Our last article mentioned the treatments most discussed at the Conference: AZT, DDC, Ampligen, peptide T, Ribavirin, alpha interferon, and AME. Here we mention some of others, in alphabetical order. We have not obtained the tapes of the meetings or been able to review all the printed information; this listing is not comprehensive.

For more information on any of the treatments listed here, see below.

Aerosol (nebulized) pentamidine. A University of California San Francisco study presented results of inhaled
pentamidine as exclusive treatment for early stage pneumocystis (nebulized pentamidine is also used to prevent pneumocystis). The treatment was successful in six of the nine patients. Of the other three, one died after five days of treatment; the other two were taken off the study within 48 hours, because their pneumocystis had progressed until it was no longer considered mild enough for inhaled medication to reach the lungs properly. The researchers concluded that inhaled pentamidine deserves more study.

Note: in San Francisco at least, many leading physicians have much interest in nebulized pentamidine, both as a
preventive and as a treatment for pneumocystis. Primary-care physicians do not need to obtain the equipment required or learn how to administer the treatment themselves; instead they can prescribe preventive doses for patients at risk, such as those who have already had pneumocystis, those with low or rapidly falling T-helper counts, and those beginning certain kinds of chemotherapy. Several other preventives for pneumocystis are also in use; no one knows for sure which is most effective. The advantage of nebulized pentamidine is that virtually no side effects have been found, even from the much larger doses used to treat the disease after it has already started.

Unfortunately this treatment is not available in most parts of the country. In some cities patients have organized a
successful effort to convince physicians in private practice or in a hospital to learn how to administer it. Since patients
receive the preventive dose only once every two weeks, they may find it practical to travel some distance for it if necessary. At least one home-care service (Caremark, in Hayward, CA) can administer preventive doses at home, when prescribed by the primary-care physician.

For more information on aerosol pentamidine, see "A Breakthrough in Treating Pneumocystis", AIDS Treatment News #23, January 16, 1987.

AL 721. One talk and one poster session at the Conference were devoted to AL 721. In addition, Yehuda Skornick, M.D. of Tel Aviv, Israel presented results of treating 28 patients; his data wasn't ready until after the Conference deadline, so he spoke at an unofficial meeting in a church across the street.

No surprises came out of these meetings; instead they strengthened what we already knew. Usually AL 721 does not
raise T-helper counts significantly, at least not for several months. Apparently it stops further decline although we don't
have scientific proof. However, mitogen skin tests, as well as HIV reverse-transcriptase assays, improved dramatically in most patients, though not in all.

Dr. Skornick's report concerned the nine of his 28 patients who had been on AL 721 for five months or longer.
Platelets improved in all of them, in one case going from 16,000 to 110,000 in a month. In most, white blood cell counts
improved. Temperature improved after 20 days. The only side effect was mild diarrhea in some. Dr. Skornick noted that several of his patients had started with very advanced AIDS or ARC, and that even cases considered terminal had been reversed.

Avarol and avarone. These naturally-occurring substances from a marine sponge have shown good results against the AIDS virus in the test tube, and have low toxicity in mice. They do cross the blood-brain barrier. A clinical trial with AIDS patients is being planned.

Bestatin. This immune modulator has been used with cancer patients. A double-blind trial on 22 HIV-positive patients
apparently did not show any benefit in immunological tests in the doses used.

Castanospermine. This substance found in an Australian chestnut inhibits the AIDS virus in the test tube, by acting
against the enzyme glucosidase I. No human tests have been done. The researchers (from Harvard Medical School, Harvard School of Public Health, and the University of Washington in Seattle) are now conducting laboratory tests to find out if castanospermine is synergistic with other antivirals.

Diethylcarbamazine citrate. A study at the Harvard School of Public Health showed some success with this drug in treating feline leukemia in cats. The researcher suggested that these results "may have implications" for the treatment of AIDS and ARC.

This poster session, presented on the first day of the Conference, would have attracted more attention if scheduled
later. For a major talk on the second day of the Conference focused almost entirely on feline leukemia ("Vaccination
Against Retroviruses, W.F.H. Jarrett, University of Glasgow, Glasgow, Scotland, available on audiotape from InfoMedix,
Garden Grove, CA., 714-530-3454 tape number T205-T6). This talk pointed out that the disease in cats is very similar to
AIDS; what it causes is not really leukemia but rather an immune suppression.

D-Penicillamine. Two poster sessions reported on the use of this antiviral in patients with lymphadenopathy or ARC. The drug clearly can suppress HIV in patients, but the doses needed to be effective often reduce T-cell numbers or cause other serious side effects.

The researchers do seem to be finding dosage schedules which can suppress HIV in patients without causing serious problems. One protocol completely suppressed HIV replication in three of five patients -- for as long as 24 weeks after treatment was stopped. The published abstracts do not report whether the patients' overall clinical condition improved.

This work is important because D-penicillamine has long been used, in high doses, for treating other diseases such as rheumatoid arthritis. It is readily and cheaply available by prescription. Side effects are serious, but they are well
known, at least for persons without HIV. The drug deserves prompt study to see whether it can be clinically useful -- as
well as to discover its mechanism of action (chelation?) and see whether variations of the molecule, or other drugs which
produce some of the same effects, could be more valuable.

For background information on D-penicillamine, contact Project Inform at (415) 928-0293.

DTC (Imuthiol). This immune modulator now looks very good. A poster session at the Conference reported a double- blind, placebo controlled study of 90 patients with ARC or lymphadenopathy at five different medical centers in France; 80 of the 90 patients had completed four months of the study and their results were reported. Impressive improvements occurred in almost every measurement taken, with no significant side effects. For example:

* In overall clinical condition, 18 of the treated patients improved after the four months, 20 were stable, one
was worse. In the placebo group, two improved, 35 were stable, three were worse. The odds of getting results this good by chance are less than one in ten thousand.

* Three of the 40 placebo patients progressed to AIDS; one died. None of the treated patients progressed to AIDS or died.

* T-helper cells in the treatment group started at an average 393 and increased by 169. In the placebo group, the
average started at 398 and increased by 38. (The increase in the placebo group was not explained. Possibly some patients obtained their own DTC on the side.)

* DTC also has some antiviral properties. The new T- helper cells do not become target for the virus.

* The number of ARC symptoms decreased, from an average of 2.5 before treatment to 1.7 after. Meanwhile, in the placebo group the number went from 2.3 to 2.1.

* After stopping DTC, the benefits were progressively lost. This treatment appears to help in the management of HIV
infection, but it is not a cure.

* Trials at six U.S. medical centers, as well as in France and in Germany, are now studying the effect of DTC on survival of AIDS patients, optimization of dosage, and combinations of DTC with antiviral drugs.

Note: At this time DTC compares very well with other possible treatments for AIDS and ARC. We now have much better information about it than about other experimental treatments which are getting more attention (such as Ampligen and DDC). DTC appears to be completely safe, is taken orally, costs almost nothing to manufacture, has shown major clinical benefit in a well-controlled trial, and would probably work even better if combined with antivirals.

But without initiative from the AIDS, medical, gay, and/or other affected communities, DTC will not become widely
available soon. This treatment, developed by Institut Merieux, a French pharmaceutical company, does not have the political clout of AZT or DDC. Notice that the preliminary report of the French study -- a double-blind trial of 90 patients at five medical centers -- rated only a poster session at the Conference in Washington, easily overlooked among a thousand other poster sessions. Also notice that the U.S. government is not helping to finance even the trial at six medical centers within the U.S., apparently because Merieux chose not to apply for U.S. funding. DTC hardly has the inside track so necessary in the U.S. drug-approval process.

How can we help to make DTC available? At least three strategies deserve to be considered.

(1) New FDA rules allowing more liberal access to experimental drugs -- providing the manufacturer is willing to
make them available for compassionate use. DTC appears to be an ideal test case. Physicians who want to get the drug may need the help of an advocacy organization or a skilled staff person or volunteer, to help them through paperwork or bureaucratic logjams.

(2) A grassroots movement could distribute DTC -- probably on the model of the DNCB "guerrilla clinics", which have
provided DNCB to about 4,000 people. DTC is fairly easy to buy, or to make in a laboratory. It appears to be both safer
and more effective than DNCB; certainly we have more scientific information about it from scientific trials.

Only one bottleneck has held back DTC so far: the difficulty of administration. The official studies use "enteric coated" capsules, which pass through the stomach and release DTC in the intestines. DTC would be destroyed by the
acidity of the stomach, and might produce toxic byproducts.

Four means of homemade administration have been proposed; at least two are in use.

(A) Enteric-coated capsules. These are quite difficult to make, but it has been done. There have been some reports of stomach irritation from these capsules.

(B) Administration by enema. This writer has heard of four persons using DTC this way; all report good or very good
results. The effects seemed to start rapidly, with people feeling better within one day. Only one enema per week is used.

(C) DMSO. This readily available solvent carries other chemicals through the skin. But one expert thought that DTC
would break down too rapidly for this method to work.

(D) Disulfiram (Antabuse). This prescription drug, given to alcoholics to prevent them from drinking by making them sick if they do, is very similar to DTC. Apparently the two chemicals exist in equilibrium in the body, meaning that if
either one is taken, a portion of it will turn into the other. For this reason, some physicians suggest that taking disulfiram
could be a way to use DTC. If so, the availability and administration problems would be largely solved. But we have
not yet heard of anyone trying disulfiram as an AIDS/ARC treatment yet.

The key to the development of a guerilla-clinic movement is the existence of instructions which enable people to use the treatment successfully. We would need a few people who would keep the instructions up to date.

Project Inform in San Francisco (415-928-0293, or toll free 800-334-7422 from California, or 800-822-7422 from other
States) is preparing an information packet on DTC.

(3) One or more organizations could start tracking the development, approval process, and accessibility of DTC, AL
721, and other drugs which deserve far more attention and official support than they are getting. Such efforts could
model themselves on environmental organizations, which study the details of natural habitats, corporate plans, and
government regulations and procedures, in order to intervene with publicity, litigation, legislation, or private purchase as
appropriate, to prevent environmental destruction. With thousands of lives already lost, and major logjams clearly visible in drug development and approval, it is surprising that no one has yet given AIDS treatments the same kind of attention and advocacy commonly received by forests, seashores, and wildlife.

Note: AIDS Treatment News previously reported on DTC in issue #29 (April 10, 1987), before the new results above were available.

In that article we reported that patients in the clinical trial at San Francisco General Hospital were told not to use
aspirin or nonsteroidal anti-inflammatory agents while they were using DTC. Since then we have heard from several sources that this restriction was not required for medical reasons. Apparently the purpose of excluding these drugs was to improve the data.


For More Information

For a copy of the Conference abstracts about treatments discussed in this article, send two dollars to: John S. James,
P.O. Box 411256, San Francisco, CA 94141. For a packet of articles by this writer on AL 721, send one dollar to the same address. For background on DTC, send a self-addressed stamped envelope to the above address.