New Treatments to Watch, 1989

Here are the potential AIDS therapies which we believe are most likely to become important in 1989.
This particular list only includes treatments for AIDS/HIV itself; therefore it omits other important new developments; for example, better antibiotics for opportunistic infections or treatments for anemia. All the AIDS therapies we selected as most promising turned out to be antivirals -- although we did not start out with that criterion.
We included only "new" treatments, meaning ones which were seldom or never available before, but might become accessible for the first time in 1989. Therefore we did not consider existing treatments such as AZT or dextran sulfate.
We based this selection mainly on "quality rumors", choosing those treatments which are generating enthusiasm among medical professionals familiar with them. A few were too new to have rumors; we included them because of the reputations of those involved in their development.
The best source for additional information about most of these treatments is the new AIDS/HIV Experimental Treatment Directory (December 1988, Volume 2 Number 3), published by the American Foundation for AIDS Research (AmFAR). The directory can be obtained from AmFAR, 1515 Broadway, Suite 3601, New York, NY 10036-8901, 212/719-0033.
* ddI (dideoxyinosine). ddI is a nucleoside analog (a drug in the same class as AZT), but appears much less toxic.
The first human trial, with 15 early AIDS/ARC patients who have now taken the drug for at least 14 weeks, started last summer at the U.S. National Cancer Institute. Another phase I (dosage and toxicity) trial is taking place at the New York University Medical Center in New York City, and the University of Rochester Medical Center, in Rochester, NY; a separate phase I trial is taking place in Boston. No human results have been published, although there are reports of patient improvements.
More importantly from our perspective, we have repeatedly heard rumors that the researchers working with ddI are very enthusiastic about it.
These rumors were indirectly supported by a dispute between top officials of the U.S. National Cancer Institute (NCI) and the Food and Drug Administration (FDA). Dr. Samuel Broder, recently appointed head of the NCI, and Dr. Bruce Chabner, director of the cancer treatment division at NCI, strongly criticized the FDA for not allowing NCI to begin tests of ddI in children under two with AIDS, before adult trials were finished. Dr. Broder himself had run the early NCI trial, the first human use of ddI; he must know as much as anyone about how to use the drug. He would hardly have made an issue of the FDA's refusal to allow immediate testing in children if problems had been encountered.
The new AmFAR directory (December 1988; see reference above) reports that ddI is believed to be ten times less toxic than AZT. "No substantial toxicity or bone marrow suppression have been noted in the NCI study; some patients have complained of mild headaches and lightheadedness. Because ddI is acid unstable, ingestion of an antacid is required prior to oral administration." The phase I clinical trial excludes persons with a history of heart disease or seizure disorder.
ddI appears to be effective in macrophages, and to be able to cross the blood-brain barrier to some extent. What will happen next? At this writing, the phase I trial in New York City and Rochester has only recruited 9 of 42 subjects. The problem is not lack of interest by patients; New York University at least has a long waiting list. The bottleneck is in the study design. Each dosage level, starting with the lowest, must be tested for several weeks before the next higher dose can be tried (in different patients); this process must continue until the maximum tolerated dose is reached. It is also rumored that limited hospital space has caused delay (each patient is hospitalized for the first two weeks of treatment, as is commonly done in phase I studies). It is possible that Bristol Meyers, which has rights to the drug, will begin a phase II trial without waiting to complete phase I, providing the FDA does not object.
ddI is easy to manufacture. If it is bogged down in red tape and institutional inertia, an underground will be inevitable.
For more information, see the latest AmFAR directory and the information cited there. For the best published report on the dispute between the NIH and the FDA, see the Chicago Tribune January 5, 1989, page 4.
* Passive immunotherapy. This treatment consists of transfusions of plasma from healthy HIV- positive donors, selected to have high levels of effective anti-HIV antibodies, to recipients who lack those antibodies because they have reached a stage in the disease where they can no longer produce them. The plasma infusions, commonly given about once a month, can be dramatically helpful even to some persons with advanced AIDS. Only about 20 people have received this treatment so far, but there is great interest among both professionals and patients.
AIDS TREATMENT NEWS has already covered passive immunotherapy, so we will not repeat the details here. For more information, see issue # 67, October 21, 1988, and issue #70, December 1, 1988. You can also call the Passive Immunotherapy Project, a patient support group organized to obtain access to this therapy, at 415/549-9137.
At this time the two major concerns about passive immunotherapy are (1) that FDA restrictions may delay access for as long as a year or more, and (2) that some physicians may offer the treatment but not do it properly, endangering their patients. These concerns may seem to be opposites, but in fact they are two sides of the same problem. For the FDA could seriously hamper the organized, professional effort to do passive immunotherapy right -- driving this treatment into the separate practices of individual physicians, where the FDA does not have jurisdiction. Excessive restriction could stymie the high- quality, organized efforts, pushing the treatment into settings where there is less quality control.
Antiviral herbs and extracts. This category consists of traditional medicinal herbs which have shown antiviral activity in laboratory tests. We listed the following three:
* Hypericin. This chemical, found in the St. John's Wort plant, appeared to be an excellent anti-retroviral when tested in animals (against retroviruses other than HIV). It also shows anti-HIV activity in the laboratory. (Since few animals can be infected with HIV, the obvious animal test against HIV infection could not be done.) For background information on hypericin, see AIDS Treatment News issue #63, August 26, 1988, and issue # 64, September 9, 1988.
So far we have received only one report of human use for AIDS/HIV, from a physician who has five patients who are using "Hyperforat", (a high-strength, standardized St. John's Wort extract available in Germany), with good to excellent results. It is generally believed that most of the St. John's Wort preparations available in the U.S. in health- food stores are worthless, because they do not contain enough hypericin, the active ingredient. Laboratory testing is now going on to see if any of the U.S. preparations appear likely to be useful.
* Compound Q. This experimental treatment (also called GLQ 223, and not to be confused with coenzyme Q), is a protein derived from Chinese herbs. It worked very well in stopping HIV in laboratory tests, but no human trials have yet been done. Apparently the drug must be given intravenously, so human experience with the herbs does not prove safety; toxicity tests are now being done in animals. The developer has applied to the FDA for permission to begin human testing.
Compound Q was developed by Genelabs in Redwood City, CA, with consultants from the University of California San Francisco, and the Chinese University of Hong Kong. The project is funded by the Swiss pharmaceutical company Sandoz Ltd., which will have exclusive rights to the product. Genelabs has previously worked with Stanford
University in screening chemicals for possible use in AIDS treatment.
For more information about compound Q, see the AmFAR directory. Or see the article on new patents in The New York Times, January 7, 1989, or U.S. patent number 4,795,739, which was issued to the researchers early this month.
* Chinese anti-infection herbs. A screening program conducted by researchers at the Chinese University of Hong Kong and the University of California at Davis tested 27 herbs and found that 11 of them showed anti-HIV activity; five of these almost completely stopped the virus in the test tube. For more information, see AIDS Treatment News issue # 61, July 29, 1988, and issue # 68, November 4, 1988.
We do not have any new results at this time. Anecdotal results seem good.

* FLT (fluorodeoxythymidine). In recent Swedish tests, FLT was found several times as effective as AZT both against HIV in laboratory cultures, and against SIV, a related retrovirus, in monkeys. The drug has previously been tried in humans, as it was tested and rejected as a cancer therapy 20 years ago in East Germany.
The recent Swedish results were announced by Professor Bo Oberg, a virologist at Sweden's Karolinska Institute. FLT is being developed by the Medivir research company, which wants to sell the patent rights to a large pharmaceutical company, probably one in the United States. Dr. Oberg previously headed an AIDS research team at Astra, the Swedish pharmaceutical company which also developed foscarnet, an anti-HIV treatment now also being used for CMV retinitis. The team screened almost 2,000 chemicals for anti-HIV activity.
FLT causes bone-marrow suppression like AZT, but it appears to have much less toxicity at an effective dose.
Dr. Oberg was quoted as saying that two years of laboratory and human testing would be required before the drug could be marketed. We suspect that this time- frame reflects the fact that FLT will probably be developed in the United States (Sweden does not have enough AIDS/HIV patients to run trials). In the past, Astra has had major problems trying to conduct AIDS research in the U.S.; see Wall Street Journal editorial of April 21, 1987 concerning Astra's frustration and withdrawal from U.S. trials of foscarnet two years ago.)
Many people would be willing to take the risk of trying FLT now, with doses based on what worked in monkeys and on human toxicity data from the earlier cancer studies. We could know in weeks or months whether or not this drug could make a substantial contribution to AIDS treatment. Red tape alone -- or rather the empires and vested interests which benefit from it -- will extends that time to years, unless the public insists that AIDS be treated as an emergency instead of business as usual.
* Azidouridine (AzdU). Formerly called CS-87, azidouridine showed no toxicity when given orally to animals in high doses. In laboratory tests, it is effective against HIV in macrophages as well as in blood cells.
The first human trial is planned for early 1989.
For more information, see the AmFAR directory.
* D4T. Animal and laboratory studies have found this nucleoside analog considerably less toxic than AZT, and about as effective in stopping HIV. Human trials are planned for early 1989. For more information, see the AmFAR directory.
* CD4. Despite the publicity about CD4, we put it last in this list of best treatments because so far we have not heard much enthusiasm from those with direct experience with the drug However, the current trials were not designed to test for efficacy, and they started with very small doses. CD4 may prove effective in further testing.