Subject: Toxoplasmosis, Chinese Herbs, Hypericin Date: Mar 10 1989 (887 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1989 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #75, March 10, 1989 CONTENTS: [***** appears here at each new item] Roxithromycin and Azithromycin: Toxoplasmosis, Cryptosporidiosis Experimental Treatments (Not in USA) Hypericin: New Dosage Information Chinese Herb Combination: Update KS: New Treatment Possibilities San Francisco: Chinese Medicine Expert to Visit, April 6-10 AIDS and Disability Rights: You Can Help Recommended AIDS Newsletters, Directories ***** Roxithromycin and Azithromycin: Toxoplasmosis, Cryptosporidiosis Experimental Treatments (Not in USA) by John S. James Roxithromycin is an antibiotic approved as a prescription drug in France; azithromycin, a similar drug, has been approved in Yugoslavia. They might be useful in treating toxoplasmosis, cryptosporidiosis, isospora (an infection which, like cryptos- poridiosis, causes severe diarrhea), and possibly MAI. Despite the need for better treatments for these conditions, we could find nothing being done or planned in the United States to learn whether these drugs might be useful. (We have heard that a trial for toxoplasmosis may start soon in France.) We publish this article to bring attention to these treatment possibilities, so that others can investigate further and organize clinical trials to determine whether these drugs are valuable for treating AIDS-related infections. Background: Toxoplasmosis Toxoplasmosis is typically a brain infection caused by the protozoan Toxoplasma Gondii (which can also affect the eye and other organs). Many healthy people are infected with the parasite, which is commonly present in cats, but usually the immune system keeps the organism controlled. At present, toxo- plasmosis is becoming an increasing problem because of AIDS, and also because of wider use of immunosuppressive drugs, for example by organ-transplant patients. Toxoplasmosis is also a threat to the fetus and newborn infant, even in healthy persons without immune suppression. Toxoplasmosis is usually treated with a combination of pyrimethamine and sulfadiazine (leucovorin must be given with the pyrimethamine). While the drugs are effective, they do not kill cysts of the parasite, so the treatment must be continued as a maintenance dose; often toxicity forces discontinuation of the drug, and relapses result. The statistics are not good, with reported death rates of about 70 percent and median survival of four months, although some people remain alive and healthy for many years after diagnosis. If pyrimethamine and sulfadiazine cannot be used, other drugs such as clindamycin or spiramycin may be used instead. It is important to start treatment early. One recent study found that one-year survival rates were greatly improved (58 percent vs 12.5 percent) in patients who were given AZT after starting the maintenance dose (Clumeck and others, 1988). But another paper presented at the same confer- ence reported that AZT interfered with the action of pyrimetham- ine and greatly reduced survival from toxoplasmosis in mice (Israelski and others, 1988). Possibly the important difference is that in the human study, the AZT was not used until after the acute therapy for toxoplasmosis had been successfully completed. A year ago (January 28, 1988) AIDS Treatment News mentioned the case of one person diagnosed with toxoplasmosis who rejected conventional treatments and used large amounts of garlic instead -- despite a physician's warning that failure to use the drugs would almost certainly result in death. This patient is still alive today. While rejecting the conventional drugs would seem to be extremely dangerous, this case suggests that there might be some value in using garlic in addition to the treatments recom- mended by physicians. It is clear that better treatments are needed. Note: due to publication deadlines we were unable to review all relevant articles before writing the background summary above. Roxithromycin and Azithromycin: Animal and Laboratory Studies At first glance, roxithromycin looks mediocre in animal stu- dies of toxoplasmosis (see discussion below). This appearance, which may be deceptive, may have discouraged wider interest in the drug. Several published studies have suggested that these drugs are worth trying for treating toxoplasmosis. Our review of these studies is in order by publication date, starting with the most recent. "Azithromycin, a Macrolide Antibiotic with Potent Activity against Toxoplasma Gondii" (Araujo and others, 1988) reported an experiment in which 10 days of treatment with azithromycin pro- tected mice after their brains were infected with Toxoplasma Gon- dii. Eight of ten of the treated mice were alive and well on day 30 after infection, while nine of the ten untreated mice were dead by the 14th day and the survivor remained ill. The researchers pointed out that compared to roxithromycin, azithro- mycin seemed effective in smaller doses. The authors concluded that azithromycin should be studied as an alternative treatment for toxoplasmosis. "Effect of Roxithromycin on Acute Toxoplasmosis in Mice" (Chang and Pechere, 1987) studied roxithromycin and other drugs, including the conventional treatments for toxoplasmosis, in mice given 500 times the 100 percent fatal dose of Toxoplasma gondii. The conventional treatment (pyrimethamine-sulfadiazine) worked well, protecting up to 100 percent of the mice, depending on the number of doses given. Roxithromycin worked less well, but it also protected up to 100 percent of the mice, depending on the dose. For spiramycin, however, only a 50 percent dose could be determined, because the mice died from toxicity of the drug before a 100 percent protective dose was reached. The authors concluded that roxithromycin might be useful for treating toxo- plasmosis, but that clinical studies would be necessary to see how it compared with other drugs. "Activity of Roxithromycin (RU 28965), a Macrolide, against Toxoplasma gondii Infection in Mice" (Chan and Luft, 1986) found that roxithromycin was effective in mice, but less so than the standard treatment, pyrimethamine and sulfadiazine. The authors suggested that roxithromycin might be a safe and effective alter- native treatment for toxoplasmosis -- presumably for use when the standard treatments fail or cannot be used because of toxicity. "In Vitro Effects of Four Macrolides (Roxithromycin, Spiramycin, Azithromycin [CP-62,993], and A-56268) on Toxoplasma gondii" (Chang and Pechere, 1988) tested the drugs in cell cul- tures in the laboratory. Roxithromycin was the most powerful, spiramycin the least. The authors suggested clinical studies of roxithromycin and other drugs. Human Experience with Roxithromycin (Not AIDS Related) Recently the British Journal of Clinical Practice published a special issue on roxithromycin (volume 42, supplement 55, 1988). This issue included several short reports of clinical trials or experience, mostly for lower respiratory tract infec- tions. These reports, from France, Austria, and Argentina, all found the drug effective. Roxithromycin is a "macrolide" -- an antibiotic in the same class as erythromycin, a prescription drug widely used in the U. S. and elsewhere for atypical pneumonias and certain other infec- tions. Roxithromycin is believed to have about the same antimi- crobial activity as erythromycin, but better bioavailability -- correcting an important shortcoming of other macrolides. Macro- lides are considered one of safest classes of antibiotics (Neu, 1988). Human Experience Relevant to AIDS In a study presented at the October 1988 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), rox- ithromycin was found to reach very high concentrations in the human brain (Manuel and others, 1988). Researchers in France and Switzerland, noting that roxithromycin had been effective in treating toxoplasmosis in mice, gave the antibiotic to volunteers who were scheduled to undergo brain surgery, so that levels in brain tissue could be determined. (These volunteers did not have toxoplasmosis or AIDS.) The four patients for whom concentra- tions were measured had much higher roxithromycin concentrations in brain tissue than in blood plasma; two had brain concentra- tions seven times as high, the other two had fifty times or more roxithromycin in brain tissue than in blood. These measurements were taken 12 hours after the last roxithromycin dose; since blood levels are known to remain high for 12 hours or more, the comparison is a fair one. This study suggests that roxithromycin is extremely effec- tive in crossing the blood-brain barrier. No other macrolides are known to behave similarly. In comparable tests in rats, roxithromycin was found not to penetrate well into brain tissue -- suggesting that the drug may be even more effective in humans than it was in the mouse studies cited above. The potential value for humans might have been missed. Another human study presented at the same conference (Kazmierczak and others, 1988) found that roxithromycin had much better blood concentrations, 12 and 24 hours after a single dose, than the two other drugs which were compared (spiramycin and trolandomycin). Taken together, these studies show that roxithromycin, a drug known to be effective against toxoplasmosis in mice, reaches a high concentration in human blood, and a much higher concentra- tion yet in the human brain, where it is needed for treating the disease. The obvious next step would be to test roxithromycin as a treatment for toxoplasmosis. We have only heard of one case where it has been tried. The physician thought that the drug (brand name "Rulid" in France) had been beneficial, but was not sure, pending study of before and after brain images. We have heard that a clinical trial of roxithromycin or azithromycin for toxoplasmosis is about to start in France, but we do not have any further information at this time. Other Opportunistic Infections A letter in the Journal of Infectious Diseases (Musey and others, 1988) reported that roxithromycin cured one case of Isos- pora belli infection, after several other treatments had failed. This infection causes severe diarrhea; the patient had had chronic diarrhea for two years. Isospora belli is closely related to Toxoplasma gondii, the organism which causes toxoplasmosis. Both are also related to the organism which causes cryptosporidiosis. Isospora is easier to treat, however, and often bactrim is effective. We heard two anecdotal reports of treatment of cryptospori- diosis with azithromycin, a drug approved in Yugoslavia which is closely related to roxithromycin. In one, we talked to a U. S. physician who was convinced that the treatment had worked very well. In the other, we heard from a Project Inform hotline volunteer that a patient had called and said that azithromycin seemed to make his cryptosporidiosis worse; this patient did not leave his name or any way to contact him, so Project Inform can- not investigate further. It is possible that roxithromycin or azithromycin may also be useful for treating MAI, in combination with other drugs. Physicians are interested because these new macrolide antibiot- ics penetrate well into monocytes; MAI is often found inside these cells. FDA Roxithromycin Controversy On December 15, 1988, The Alternative, a Baltimore gay paper which often publishes important, original investigative stories on AIDS treatment research and public policy, reported that a major drug company had applied to the FDA for an IND (Investiga- tional New Drug approval) to study roxithromycin and azithromycin in clinical trials, but that the FDA had rejected the application due to lack of adequate animal studies -- even though roxithromy- cin was already approved and in human use in France. (Roxithro- mycin was later mentioned in U. S. News and World Report, Febru- ary 13, 1989, page 82.) We called the FDA and the drug company (Roussel, a French company which also has offices in New Jersey), and found that the agency and the company had different understandings of the facts of this case. The misunderstanding, which came to light by accident, may have helped cause the proposed research to be can- celled. Both agree that the company did apply for an IND (Investiga- tional New Drug approval, meaning permission to test the drug on humans), and that the FDA asked for animal studies. The IND application was to study roxithromycin for AIDS-related cryptos- poridiosis and isospora -- not toxoplasmosis. The animal studies were to answer certain questions concerning the rationale of the treatment -- not to test roxithromycin as if it were a new chemi- cal which had never before been given to humans. The question at issue is whether the drug was rejected because animal tests showed it was unpromising for cryptospori- diosis and isospora -- or whether it was dropped without any tests because of the expense or impossibility of obtaining the information requested. The FDA spokesperson we talked to believed that the company did do the studies, and based on the results decided it was unlikely that the drug would be effective, and therefore decided not to pursue human trials. He suggested a person at Roussel whom we could call for further information. We called that person, who needed to check further, as we had called asking about toxoplasmosis, but he had been prepared to reply about cryptosporidiosis and isospora. Our concern was that people were starting to use the drug, and if animal studies had suggested that it would be ineffective, it was urgent that the information be known. After checking with other people in the company, the Roussel spokesperson called us back and told us that no such animal stu- dies had been done. Instead, after the FDA asked for those stu- dies to confirm the activity of the drug, the researchers at Roussel found no good animal models to answer the questions asked, so the company decided not to pursue the project. The spokesperson also confirmed that the IND application had not con- cerned toxoplasmosis. Today we know of no plans in the U. S. to study roxithromy- cin for any AIDS-related condition. There may be a toxoplasmosis study soon in France. Roxithromycin -- the Next Step As many as 31,000 persons with AIDS may develop toxo- plasmosis by 1991 (Potasman and others, 1988); with conventional treatments only, most of them will die. Obviously clinical tri- als of promising treatments like roxithromycin are needed. Physicians, scientists, and regulatory officials may have missed the importance of roxithromycin, thinking that it could not be a major advance because in the test tube and in animals it is no more effective than the conventional treatment for toxo- plasmosis, and perhaps somewhat less effective. The implication that roxithromycin is therefore unimportant is probably errone- ous, for two reasons. First, it overlooks the strikingly high concentration of roxithromycin in brain tissue, where toxoplasmosis is located. This very good penetration into the human brain is not found in the rat, so animal experiments would not be expected to show the benefits which might be found in humans. The study (cited above) which found the high concentrations in human brain tissue was presented as a poster session at the ICAAC conference last October, and may not be widely known. Second, the comparative efficacy against Toxoplasma gondii is not the important question here. Both roxithromycin and pyrimethamine/sulfadiazine (the conventional treatment) are clearly effective, though neither kills Toxoplasma entirely. The problem with pyrimethamine/sulfadiazine is that toxicity develops, preventing long-term use and resulting in relapse when the drugs can no longer be used. Roxithromycin has very little toxicity, so it could probably be used for a long time. At the very least, roxithromycin should be tried in cases when there is no other option. The central problem seems to be that no one is making sure that even the most obvious and fundamental interests of persons with AIDS or at risk for AIDS are considered when drug-develop- ment decisions are made. We need leadership from the medical community, as well as from patient-advocacy groups. Until trials can be arranged, the second best option is to obtain roxithromycin from France, or send patients there, and collect anecdotal information. The PWA Health Group recently listed roxithromycin as one of the prescription drugs it wants to make available (see "AIDS Group Organizing Imports of Drugs Not Approved by F. D. A. ", The New York Times, March 6, 1989, page 1). References Araujo, FG and others. Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii. Antimicrobial Agents and Chemotherapy, volume 32 number 5, pages 755-757, May 1988. Chan, J and Luft, BJ. Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice. Antimi- crobial agents and chemotherapy, volume 30 number 2, pages 323- 324, August 1986. Chang, HR and Pechere JF. Effect of roxithromycin on acute toxo- plasmosis in mice. Antimicrobial Agents and Chemotherapy, volume 31 number 7, pages 1147-1149, July 1987. Chang, HR and Pechere JF. In vitro effects of four macrolides (roxithromycin, spiramycin, azithromycin [CP-62,993] and A- 56268) on Toxoplasma gondii. Antimicrobial Agents and Chemoth- erapy, volume 32 number 4, pages 524-529, April 1988. Clumeck, N. and others. The benefit of zidovudine on the long- term survival of AIDS patients with CNS toxoplasmosis.Program and Abstracts of the Twenty-Eighth Interscience Conference on Antimi- crobial Agents and Chemotherapy, abstract number 1474, Los Angeles, 23-26 October 1988. Holliman, RE. Toxoplasmosis and the acquired immune deficiency syndrome. J. Infect., volume 16 number 2, pages 121-128, March 1988. Israelski, DM and others. AZT antagonizes pyrimethamine in experimental infection with Toxoplasma gondii. Program and Abstracts of the Twenty-Eighth Interscience Conference on Antimi- crobial Agents and Chemotherapy, abstract number 349, Los Angeles, 23-26 October 1988. Kazmierczak, A and others. Roxithromycin pharmacokinetic com- pared with those of spiramycin and trolandomycin after a single oral dose. Program and Abstracts of the Twenty-Eighth Intersci- ence Conference on Antimicrobial Agents and Chemotherapy, abstract number 137, Los Angeles, 23-26 October 1988. Manuel, C and others. Penetration of roxithromycin into brain tissue. Program and Abstracts of the Twenty-Eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, abstract number 1224, Los Angeles, 23-26 October 1988. Musey, KL and others. Effectiveness of roxithromycin for treat- ing Isospora belli infection. The Journal of Infectious Diseases, volume 158 number 3, page 646, September 1988. Neu, HC. Roxithromycin -- an overview. The British Journal of Clinical Practice, volume 42 supplement 55, pages 1-3, 1988. Potasman, I and others. Intrathecal production of antibodies against Toxoplasma gondii in patients with toxoplasmic encephal- itis and the acquired immunodeficiency syndrome (AIDS). Annals of Internal Medicine, volume 108, pages 49-51, 1988. ***** Hypericin: New Dosage Information The last issue of AIDS Treatment News (#74, February 24, 1989) included a major report on human experience with hypericin, an experimental antiviral readily available in certain extracts of the St. John's wort plant. The following updates are based on information we received after the article was published. Dose Calculation Error In our February 24 article, we calculated equivalent doses for the Hyperforat tincture from Germany, and St. John's wort tablets (Yerba Prima Botanicals) which are more available and convenient, and less expensive (page 4 of that article). We cal- culated that the 120 drops of Hyperforat (the dose with the most human experience so far) would be equivalent to three and a half of the tablets, each of which contains 250 mg of 0.14 percent hypericin. (Both products are standardized for hypericin con- tent, so different lots should have the same strength.) Since the article was published, a chemist told us that our calculations were probably incorrect. According to his informa- tion, the correct dose would be about two tablets, not three and a half, to be equivalent to 120 drops of Hyperforat tincture. Our error was that when we converted drops to milliliters, in order to calculate the amount of hypericin in 120 drops of tincture, we used a ratio of 20 drops per milliliter, a standard conversion factor in medicine. However, the chemist explained that the 20 drops applies to pure water, but that a mixture of water and alcohol, as found in herbal tinctures, has different surface characteristics resulting in smaller drops. He estimates that there would be 40 to 45 drops per milliliter. We could not obtain the Hyperforat product by press time for a direct test, but two other hypericin tinctures we tested both fell within this range. If Hyperforat does also, then the 120- drop daily dose of that product would be equivalent to somewhat less than two of the tablets, instead of three and one half -- based on the specified hypericin content of the two products. Animal Studies Suggest Less Frequent Use We spoke again with the team at New York University which did the laboratory and animal studies published last July in the Proceedings of the National Academy of Sciences, USA. In further animal studies, they have consistently found that giving hyperi- cin less often than once a day has worked better as an antiretro- viral than giving it every day. For example, a single dose of ten micrograms was less effec- tive than a single dose of 100 micrograms. But ten daily doses, of ten micrograms each, worked less well than even the single 10 microgram dose. The animals were given larger doses relative to body weight than people have been using. The scientists emphasized that this information should in no way be interpreted as recommending any specific dose at this time. The researchers are now preparing their animal results for publication, but the paper will not be published for several months at least. They pointed out that there is no guarantee that findings in animal studies will apply to humans -- or to HIV, which in laboratory tests seems to be more sensitive to hypericin than the animal retroviruses they had been using -- and that only clinical trials can determine the best dose and schedule for human use. Editorial Comment: At this time there is no human experi- ence with a less frequent schedule. Everyone we have talked to who has used St. John's wort extracts has used them every day -- as recommended for antidepressant use in Europe. In the reports so far, clinical benefits have usually been found within three to four weeks of starting daily use of stand- ardized hypericin preparations (See AIDS Treatment News issue #74). Therefore within a month it might be clear whether or not the treatment is working for a patient. If not, the treatment might be discontinued; if it is working, then if the person decides to change to a less frequent dosage schedule, the bene- fits already seen can serve as a baseline for comparing whether or not the new schedule seems to be better. More Good News -- But Caution Needed Before going to press we asked Dr. David Payne, four of whose patients have been using hypericin for three to four months, if there was any new information in the two weeks since we published our last issue. All four of them have continued to improve clinically. T-helper count increases have remained disappointingly slow -- not surprising since these patients started with counts less than 10. In our last issue we reported that one of the four patients had gone from P24 antigen positive to negative while using hyper- icin. Results are now back on two of the others. One of them has also gone from positive to negative. The other has remained positive, but the antigen level improved, from over 400 to 117. The fourth patient was P24 negative from the beginning. Despite the continuing good results, the information so far available about hypericin is very preliminary. No one knows the best dose or dosage regimen, no one knows which patients may be most likely to benefit, and no one knows if the herbal extracts will prove effective or even safe in long-term use. It is impor- tant that some people try hypericin, so that we will find out soon whether or not it is useful; that is already happening. But it would be risky for this treatment possibility to come into widespread use before more is known. There is no great rush to start using hypericin. The larg- est buyer's club, the PWA Health Group in New York, received many calls about St. John's wort extracts, but sold only a few dozen bottles in the week after our article came out. The Healing Alternatives Foundation in San Francisco has also had only moderate sales. Fortunately, people are being cautious. Or perhaps a treatment which costs about 25 cents a day is unlikely to be taken very seriously. Because there have been many disappointments before, includ- ing some treatments which looked good at first but turned out to be harmful, we emphasize again that no one knows how hypericin will turn out, and therefore caution is important. Note: As we went to press we heard from a physician that one patient using St. John's wort tablets and no other treatment had a liver function test result four times normal -- which might or might not have been caused by the herbal extract. This case reinforces the suggestion, published in our last issue, to have one's physician monitor a blood-chemistry panel when using hyper- icin. The research team at New York University found small, tem- porary changes in liver function and other blood-chemistry values in some rhesus monkeys given the chemical. We do not know what tablets were used, or what dose, or how long. Dr. Payne checked the records of his four patients who had used hypericin for three months or more, and found no such prob- lem. Two had elevated liver enzymes before starting hypericin; both have improved while they used it. A third had a slight elevation while on hypericin; however, he had done well enough to resume AZT, which could have been the cause. The fourth was nor- mal throughout. ********** Chinese Herb Combination: Update Six months ago AIDS Treatment News interviewed Keith Barton, M. D., a physician trained in acupuncture and Chinese herbal treatment as well as Western medicine. Dr. Barton had prepared a combination of six herbs traditionally used as anti-infection treatments in Chinese medicine, and which also had shown anti-HIV activity in laboratory tests. We reported that of the first two patients who used the combination, one had gone from P24 antigen positive to negative in three weeks -- a good early sign. Recently Dr. Barton told us that this particular herbal com- bination has not proved effective. The patient whose antigen had gone to zero had started at a very low value. Later, he went off the herbs in order to begin another treatment program, and his antigen level subsequently rose. Three other patients who took the same combination have not shown P24 antigen improvement. Some of them have a higher T- helper cell count than when they started the herbs, but the rises are not large enough to rule out laboratory error. The six herbs used in this combination were Lonicera japon- ica, Lithospermum erythrorhizon, Prunella vulgaris, Viola yedoensis, Epimedium grandiflorum, and licorice root. There are other Chinese herbal combinations which might prove effective and have not yet been evaluated. Also, Dr. Bar- ton pointed out that only a highly effective treatment would be identified by the protocol he used. ********** KS: New Treatment Possibilities by Denny Smith In January AIDS Treatment News (#73), reported on conven- tional treatments for Kaposi's sarcoma which have been adapted to HIV-related KS. Those included the careful use of radiation therapy, and chemotherapy administered intravenously or intrale- sionally. Recently, at least three more treatments have entered the field: the Prosorba column, interferon, and laser surgery. The Prosorba column, also known as a protein A column, and the interferons alpha and beta are systemic approaches to KS (like intravenous chemotherapy). The use of lasers (like Velban injec- tions or irradiation of specific lesion sites) is a localized treatment. Whether to consider a systemic treatment or a local- ized one depends on the growth and location of the lesions, as we described in the earlier article. Lasers are currently being used to remove lesions in the mouth and esophagus, tissues which can become severely inflamed if treated with radiation. Herbert H. Dedo, M. D., of the University of California at San Francisco has used lasers for fifteen years to treat cancer and to remove warts or scar tissue. He feels that treatment of lesions in the oral cavity is war- ranted if they have become symptomatic -- if they functionally impair swallowing or breathing. The procedure is done under gen- eral anesthesia and is usually followed by an overnight hospital stay. To gain access to the lesion, Dr. Dedo employs a retrac- tor he designed himself, and with an operating microscope as a visual guide he aims a laser at the targeted lesion for a dura- tion calculated in fractions of a second. The lesion is vapor- ized, and the surrounding blood capillaries are cauterized by the laser's action. The patient may experience some soreness at the site for a few weeks, but less than a surgical excision would cause. The Prosorba column was first developed to treat cancer, and then was found to be useful against HIV-related ITP (idiopathic thrombocytopenic purpura). Dobri Kiprov, M. D., director of the plasmapheresis unit at Children's Hospital in San Francisco, has had over four years of experience using the Prosorba device for KS. He has seen a response rate (lesion regression or stabiliza- tion) of about 42%. The response in patients with ITP was higher, between 50 to 60%, but the KS application may still be refined to obtain a better result. The Prosorba column appears to be a simple procedure, but operates on a mechanism of action not fully understood. The object of this treatment is to remove from the bloodstream substances called circulating immune com- plexes (CIC), and other "blocking factors", which some research- ers feel are an obstacle to a normal immune response. According to this logic, the removal of some CIC could trigger an effective attack against the antigens responsible for KS and ITP. To accomplish this, a unit of blood is drawn from the patient and processed in a centrifuge, where cells are separated from plasma. The cells are returned unaffected to the patient, but the plasma is run through a column of silica which has been coated with "protein A". This protein binds with a type of immu- noglobulin, the CIC targeted for removal. The plasma is then returned to the patient. Side effects appear to be slight but common -- mostly fevers and chills. The treatment can be repeated periodically. Dr. Kiprov feels that circulating immune complexes may play a role in the development of ARC or AIDS, and that the Prosorba column, in addition to filtering out CIC, might potentiate the body's immunity by stimulating production of interleukin, and other components of the immune system. This treatment is still under investigation and is done under a research protocol. Interferon is a protein naturally secreted by cells in response to viruses, bacteria, and other antigens. Occurring in three distinct classes, alpha, beta and gamma, interferon stimu- lates surrounding cells to manufacture other proteins which in turn inhibit antigen growth or replication, and which enhance an appropriate immune response. It is the body's most rapidly pro- duced defense. In related experiments, all the interferons demonstrated in vitro anti-HIV activity, and interferons alpha and beta were shown to have anti-tumor activity. At least 12 studies presented at the IV International Conference on AIDS in Stockholm last June discussed the value of interferon as a treat- ment for KS. The results were uneven, but several reports sug- gested that interferon is more effective if given when T4-helper cell counts are over 200, and may work in synergy with AZT. Last November the FDA approved the use of recombinant alpha interferon for treating KS, based on a lesion-reduction response in 40 to 45% of patients receiving a high dose. In December, AIDS Treatment News (#70) spoke with Mathilde Krim, Ph.D., found- ing co-chair of of the American Foundation for AIDS Research, who felt that the dose upon which the FDA based its approval was unnecessarily high: 20 million units or more daily. (The dose is usually lower when administered concurrently with AZT). Tri- als are still in progress which will hopefully determine the optimum therapeutic index (the ratio of an effective dose to a toxic dose). In any event, the side effects of large doses almost always include persistent flu-like symptoms. Meanwhile, other potential KS treatments are being investi- gated, and we will watch for any good results. They include beta interferon, tumor necrosis factor, cryotherapy, colony stimulat- ing factor, CL246,738 and interleukin-2. ********** San Francisco: Chinese Medicine Expert to Visit, April 6-10 Dr. Wei Bei-Hai, Director and Chief Physician of the Beij- ing Research Institute of Traditional Chinese Medicine, will give lectures, workshops, and consultations in San Francisco, April 6- 10. Dr. Wei was trained in Western medicine and has been work- ing with the integration of Western medicine and traditional Chinese medicine (TCM) for 30 years. Lecture topics include: Chinese medicine and the theory of immunity; treatment of chronic viral infection through combina- tion of Western and TCM therapies; TCM treatment of diabetes; and TCM treatment of physical weakness in the elderly. Dr. Wei will also give individual consultations. These would be especially valuable for local TCM practitioners who want to bring a patient to see Dr. Wei. For more information or to schedule an appointment, call Ann Rosencranz, Quan Yin, 861-4964. Quan Yin Note Quan Yin Acupuncture and Herb Center, Quan Yin Healing Arts Center, and Quan Yin Herbal Program, are moving a few blocks to larger quarters, at 1748 Market St., San Francisco, starting April 2. The phone numbers will stay the same. The public is invited to a grand opening party at the new location, Saturday, April 8th, 8-10 PM. ***** AIDS and Disability Rights: You Can Help Congress will soon consider the Americans with Disabilities Act, a landmark bill to protect all disabled persons against discrimination. Disability activists have commendably insisted on including all disabled persons equally, instead of allowing different disease constituencies to be split by political trade- offs. The AIDS community owes a debt to the larger disability community, which has refused to abandon persons with AIDS to appease bigots. We can begin to repay the debt when the Act is introduced, by working all-out for its passage. However there are still attempts to exclude persons with HIV from legislation to protect other disabled persons. To resist these attempts, the delegate from NAPWA (the National Association of People with AIDS) to the Congressional Task Force on the Rights and Empowerment of Americans with Disabilities wants to hear about cases of AIDS- or HIV-related discrimination -- in medical care, employment, public accommodations, or otherwise. If you or anyone you know has experienced such discrimina- tion, write a short account -- half a page is usually enough -- and send it to David Bodenstein, National Association of People with AIDS, 2025 I St. NW, Suite 415, Washington, DC 20006. Please include a phone number or address where you can be con- tacted. Your name will be kept confidential; or you can write anonymously if you prefer. ***** Recommended AIDS Newsletters, Directories We have found the following newsletters and directories (listed alphabetically) among the best sources of current AIDS treatment information. * The AIDS/HIV Experimental Treatment Directory is compiled and published quarterly by AmFAR ( the American Foundation for AIDS Research), and includes a comprehensive list of antivirals and immune modulators for which clinical trials are currently ongoing or are planned. Treatments for opportunistic infections are described more briefly. The directory also includes informa- tion about the current status of clinical trials, such as the purpose and duration of the trial, the criteria for being included or excluded, and the names of the manufacturers and investigators. It often has information not otherwise published or available, obtained from interviews with researchers. A sin- gle copy is $10 -- free for persons with HIV who cannot afford it. Annual subscription is $30. To order the directory by phone, call 212/719-0033; by mail, send a check to: AmFAR, 1515 Broadway, Suite 3601, New York, NY 10036. (Note: the February 1989 issue is a special edition titled A Practical Guide to Clin- ical Research. It is a handbook for people considering volunteering for clinical trials.) * AIDS Medical Report, published monthly by American Health Consultants is a journal of in-depth articles on the treatment of HIV-related disorders. Articles are written for physicians but are usually quite readable by patients. To subscribe, write AIDS Medical Report, 67 Peachtree Park Drive, NE, Atlanta, GA 30309; subscriptions are $109. per year. Note: We do not recommend the "special reports" also sold by the publisher. The ones we have seen seem overpriced, and not as useful as the newsletter itself. * AIDS Targeted Information Newsletter (ATIN) is a monthly collection of abstracts selected from recent medical literature. Many are highly technical, written for scientists and physicians. They are grouped into eight areas: molecular, virological, immu- nological, epidemiological and clinical research, treatment and assay methods, and ethical/legal concerns. To order ATIN, call 800/638-6423. In Maryland call 528-4105 collect. Subscription price is $125.00 per year individual, $275.00 for institutions. * Bulletin of Experimental Treatments for AIDS (BETA) is published by the San Francisco AIDS Foundation. Two issues have appeared to date; the first focused on AZT, the second on other, experimental antivirals, with an update on AZT. They provide a very good overview of promising options for HIV intervention. BETA is free to residents of San Francisco. To subscribe, call 415/861-3397. * The Directory of Antiviral and Immunomodulatory Therapies for AIDS (DAITA) is published by CDC AIDS Weekly (a privately published AIDS newsletter not connected with the Centers for Disease Control). This directory aims to be complete, to review "current published research on every drug or therapy that has been presented as a potential treatment for AIDS" -- but as the name implies, it does not include treatments for opportunistic infections. DAITA differs from the AmFAR directory (see review above) in several ways. It includes all antivirals or immune modulators (AmFAR often omits those which appear unpromising), usually reviews published information only (AmFAR also includes original reporting), and does not have the detailed information about clinical trials which AmFAR's directory does. We find DAITA a handy reference for basic information when we hear about proposed treatments with which we are not familiar. DAITA costs $26 for the current issue. For ordering information, call CDC AIDS Weekly, 205/991-6920. * P. I. Perspectives is a quarterly journal from Project Inform. It often covers public policy issues (drug access, FDA regulations), as well as treatment information. Project Inform has long endorsed early intervention for HIV infection, and has developed a "treatment strategy" to help people who are HIV- positive make choices about monitoring and treatment to stay healthy. To receive the treatment strategy information, P. I. Perspectives, and in-depth writeups of several popular treat- ments, people outside of California can call 800/822-7422; from California outside of San Francisco call 800/334-7422; from San Francisco (and from outside the United States) call (415)558- 9051. There is no charge, but a donation is requested. * Treatment Issues is published ten times a year by the Gay Men's Health Crisis. A wide range of excellent articles has covered new anti-HIV drugs, immunomodulators and treatments for all the major opportunistic infections. Articles are useful for both patients and physicians. To subscribe, write to GMHC, Dept. of Medical Information, 129 W 20th St., New York, NY 10011. A $20 donation is requested for those who can afford it. ***** Statement of Purpose AIDS Treatment News reports on experimental and complemen- tary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists physicians, and other health practitioners, and per- sons with AIDS or ARC. Long-term survivors have usually tried many different treat- ments, and found combinations which work for them. AIDS Treat- ment News does not recommend particular therapies, but seeks to increase the options available. We also examine the ethical and public-policy issues around AIDS treatment research. ***** [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display