AIDS TREATMENT NEWS No. 051 - February 26, 1988

The biweekly newsletter AIDS Treatment news began as volunteer research and writing for an AIDS archiving organization in San Francisco. In little over a year it has grown to a circulation of over 3,500 almost entirely by word of mouth--an unexpected public response which illustrates the critical dearth of practical treatment information felt by patients and physicians alike. Researching treatment articles for AIDS Treatment News has provided an unusual opportunity to hear what this community would like to see happen, and where it sees the obstacles now.

People react to an AIDS diagnosis in different ways. Some resign themselves to dying and begin to prepare for death. Others ask their doctors to make the medical decisions for them, without their personal involvement. I do not have contact with these people and do not know what they feel about treatment research and access issues.

But very many persons with AIDS or other HIV infections choose to involve themselves in decisions about their health care. They often become experts in the disease and potential treatments.

And most of these people come to feel abandoned and betrayed by society. They believe that many physicians, researchers, and officials have been quick to write them off as already all but dead--despite all the unknowns about this disease which make it impossible for anyone to be sure that death is inevitable. The projected deaths of at least a quarter of a million Americans seem to have been accepted with surprising equanimity and surprisingly little sense of crisis or mobilization.

Oddly enough there seems to have been no professionally conducted survey asking the persons most directly affected by AIDS what they thought about the issues of treatment research and access now before this Commission. Certainly the people I know have never been asked how they see the situation, what problems they find in the institutional response to the epidemic, and what improvements they would suggest.

A Wish List Since we have no scientific survey information on what people with AIDS would most like to see done, we did the next best thing and interviewed Nathaniel Pier M.D., a physician with a large AIDS practice in New York City. We have found his statements about what is needed to be as close as anyone's to the beliefs of the persons with AIDS with whom we have communicated while writing AIDS Treatment News.

Dr. Pier proposed above all "That anybody diagnosed with HIV- related disease or immunodeficiency be given a full assessment of their situation and be allowed to choose to receive a therapeutic regimen or decline it. Theoretically, all five hundred thousand persons infected in New York should be allowed access to some form of therapy if they wished. To satisfy scientific needs, they could be enrolled in formal protocols. Otherwise clinicians should be allowed to use empirical regimens, with patients properly monitored.

"This way everybody would be given the optimal chance to save their lives and nobody would be allowed to twist in the wind. Furthermore, we could look at the results--and get a sense of what works much more rapidly than under the current system.

"Persons could use single drug treatments, or rational combinations based on the best judgment of experienced physicians. "What we propose here is what is already done with cancer patients. Almost no one diagnosed in the United States today with cancer is denied an opportunity to participate in potentially lifesaving therapy. There is in place a widely accepted system for providing these experimental and established therapies to cancer patients. This system advances our knowledge of the treatments for this disease but is also a humane and compassionate way of caring for patients.

"To the argument that there are no AIDS treatments except AZT because no others have proven effective, we would answer that we are currently capable of choosing safe, rational approaches to therapies. In addition, people are using therapies anyway. Our proposal would allow them to do so under supervision, so this can be done safely and the data developed can be critically evaluated and thereby be helpful to others instead of remaining anecdotal." Some Problems "It is clear that the best hope for people with immune deficiency or at risk for the illness is the rapid development and dissemination of safe and effective therapies. Until this goal is achieved, the most humane approach to dealing with AIDS and AIDS-related problems is to give people access to supervised therapeutic protocols. The main problem, therefore, is to develop such a system--a system that would allow rigorous scientific analysis of therapies and still incorporate anyone wishing to try to help themselves with experimental therapies.

"The present system for developing AIDS therapies has been painfully slow in starting. Access is so severely limited that the majority of people affected by this disorder are left without intelligent recourse.

"In addition it is unclear where the leadership for determining priorities in therapy development is coming from. It is also unclear how the decisions for prioritizing the various therapeutic approaches are being made. For people with AIDS it is unclear who is setting the timetable and who is supervising the large-scale effort to develop therapies.

"For the individual who must make decisions there is no centralized method of gaining access to the information that will allow him or her to choose the best course of action.

"How does the present system work? As an example, we submit correspondence relating to a potential therapy for AIDS which first was recognized in 1984. In spite of prominent AIDS researchers acknowledging the potential benefit of this therapy, no clinical trials on humans with HIV infection have been initiated since then. In addition, you will see that letters to the people vested with protecting the public health have gone ignored and unanswered. This has left the impression that they are inefficiently and callously dealing with this very important issue. We do not believe that this is truly the case. Nevertheless the letters have gone unanswered and the trials have not materialized." Other Concerns Lentinan. Dr. Pier's statement above concerns his two-year attempt to get this drug considered. We should point out that lentinan has long been used for cancer treatment in Japan, with complete safety. And a letter to The Lancet (October 20, 1984), signed by seven scientists including Robert Gallo M.D. describes its use in the successful treatment of two patients which retroviral infections (one with HIV, the other with HTLV-I).

In four years nothing has been done. Examination of Dr. Pier's correspondence with governmental authorities clearly illustrates the frustration and difficulty he experienced in attempting to get this potential treatment considered on its merits. Now we have heard that NIH has put lentinan into its highest priority category for investigation--without major new information, essentially on the basis of what was known four years ago. However the drug-selection process is secret so we only have hearsay and have not been able to confirm that lentinan has been placed into the high priority category, or that it was done without new information.

AL 721. The unhappy story of the repeated failures to test this drug properly and make benefits available is presented at length in the back issues of AIDS Treatment News, submitted into the record of this hearing.

In yesterday's hearings one of the Commissioners asked FDA Commissioner Dr. Frank E. Young if a therapy might be developed to help overcome drug abuse, which is becoming so important in the spread of AIDS. AL 721 was in fact first developed primarily for that purpose. Theory, laboratory, and animal studies have suggested that it might be effective in reducing the symptoms of opiate or alcohol withdrawal, thus helping abusers to overcome their habits permanently. However to our knowledge no human study has been done--not even a small, quick, inexpensive pilot study which would give some sense of whether it was worth proceeding with this potential medical intervention against drug abuse.

Trimetrexate. The important news about the approval of the first AIDS-related treatment IND has failed to acknowledge a major concern. Theory and laboratory studies suggest that the trimetrexate with leucovorin therapy now approved for pneumocystis pneumonia (when standard therapies have failed) would very likely also work against cryptosporidiosis, a severe and often fatal diarrheal illness of persons with AIDS. Cryptosporidiosis presently has no satisfactory treatment.

We have heard that even a leading gastroenterologist has been unable to obtain trimetrexate for compassionate use for treating cryptosporidiosis. We have also learned that the manufacturer, Warner Lambert, has no plans to develop the drug for this condition.

The result is that this drug, already proven so safe in persons with AIDS that almost none of the (pneumocystis) patients had to have the therapy terminated, will never be tested for cryptosporidiosis under the current system, despite the immense benefit the discovery of a successful therapy for this opportunistic infection might bring.

Salk Polio Vaccine. The "old" Salk killed-virus polio vaccine (not to be confused with Salk's current work on an HIV vaccine) has recently been tried as a possible ARC or AIDS treatment. Although it is far too early to be sure it is effective, this therapy has generated considerable excitement among the physicians who have seen the results. In addition, according to an overview article which appeared in The Wall Street Journal on January 27, 1988, this possible therapy has also attracted unusual attention from some NIH scientists, who have determined that persons receiving repeated treatments with this vaccine have produced neutralizing antibodies against the AIDS virus. We have heard that Dr. Pitts is now collaborating with a university and a county board of health on a formal study, approved by his IRB--but that Dr. Pitts and a colleague must pay for the vaccine out of their own pockets.

We have also heard two reports that Connaught Laboratories Inc., the only company able to sell the Salk polio vaccine in the United States, has recently made it difficult for physicians to obtain supplies for use in treating AIDS--even though it is perfectly legal for physicians to use it for that purpose. One internist told us that the company refused to ship the vaccine unless he signed an affidavit that it would only be used to immunize against polio. And we also heard that Dr. Pitts' group had to th reaten a lawsuit in order to obtain supplies for the study cited above.

We have been unable to confirm these reports because Connaught has refused to discuss them. It is widely believed in the AIDS community that companies do not on their own resist the development of new markets for their products. It is generally presumed that these cases reflect fear by the company of making enemies at the FDA, which may fear damage to the regulatory process from the development of a public demand for a drug outside of normal channels. Bureaucratic interests may be best served if the usefulness of a valid AIDS treatment is never discovered in the first place. Patients' interests differ. All this in conjecture, of course, as in these cases no one talks, and unless an insider reveals information nothing can be proved.

The polio-vaccine case is not at all unusual. In case after case, too numerous to list here, deliberate roadblocks and obstacles have impeded patients in obtaining treatments, and prevented research which could serve as early pilot studies to indicate whether or not an idea deserved further, more formal trials.

Recommendations 1. That either the Commission or another body investigate the problems cited above, and dozens of similar ones which we can bring forward, to find out what did happen, if there are indeed roadblocks to treatment and treatment research, and how these roadblocks could be overcome.

2. That the Commission arrange for a survey to ask persons with AIDS, ARC, and asymptomatic HIV infection what they think about current public policies regarding the epidemic, and how those policies might be improved.

3. That the Commission ask the FDA to provide guidelines to researchers outlining what studies would be required to qualify a drug for treatment IND or for approval. These guidelines should specify when it is and is not ethical to use placebos in persons with life-threatening disease, or to withhold use of previously proven therapies such as pneumocystis prophylaxis.

4. That the Commission recommend the creation of a public, computerized and printed registry of all human trials for treating AIDS and related disorders. This registry should include pertinent information about each drug, and the protocols, in language that can be understood by a lay person. Registration in this database should be required for all government-funded protocols, and voluntary registry of all others should be encouraged.

5. That the Commission recommend steps to make access to therapeutic trials equally available to all qualified persons. A system must be established for insuring fair access to everyone in need. A lottery might be suggested.

6. That the Commission suggest the creation of a confidential, voluntary registry of individuals affected by AIDS and related disorders, whereby these individuals can be notified automatically when there are new trials for which they can qualify. (This system could also help researchers recruit for their trials.) 7. That the Commission recommend the immediate expansion of funding for experimental trials organized and run at the community level, using the resources of private and community physicians, such as the Community Research Initiative in New York, and the County Community Consortium in San Francisco.

8. That the Commission encourage the current attempts to share and disseminate reagents, materials, and scientific data within the scientific community, to speed the discovery of safe and effective therapies for AIDS.

9. That the Commission recommend the development of a system such as compulsory licensing which would prevent proprietary restrictions on data and access to drugs from impeding development of AIDS treatments.

10. We urge the Commission to recommend that individual patients and their physicians be allowed to choose to use safe experimental therapies under supervision, even before efficacy has been confirmed, if informed consent is obtained.