Subject: Carrisyn; Fusidic; Dextran; New Studies Date: May 2 1988 (736 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& TREATMENT ISSUES -- The GMHC Newsletter of Experimental AIDS Therapies &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Volume 2 Number 3 May 2, 1988 In this issue: Ampligen The Immune System and GM-CSF Dextran sulfate and the NIH New Studies In Brief Ampligen Encouraging initial results of a pilot study treating 7 ARC and 3 AIDS patients for about 4 months with Ampligen were reported last June in The Lancet (1). Recently reported ongoing results of the study continue to be promising (2). It appears that, at the least, Ampligen treatment can relieve common symp- toms such as fatigue, and perhaps halt or slow progressive deterioration of the immune system. A multicenter placebo- controlled trial is underway in ARC patients and an open label (no placebo) trial in AIDS patients is just starting at the Com- munity Research Initiative. The present article is an in-depth look at this potential AIDS therapy. Background RNA is one of the substances found in every cell which comprise the "genetic code" of the cell. The genetic material of HIV, the Human Immunodeficiency Virus, is also composed of RNA. When a cell is infected with a virus and foreign RNA is made, many responses are triggered to thwart the virus' replication. These responses include interferon synthesis, induction of cer- tain anti-viral substances, activation of natural killer cells and generally enhanced immune responses (3). Ampligen is a syn- thetic RNA which can be thought of as a "phony virus" and which stimulates these same components of the immune system. Thus, it appears to be both an antiviral and an immune-boosting drug. Furthermore, it appears to have no toxic side effects, crosses the blood brain barrier, and is synergistic with AZT against HIV. Ampligen's history Various double-stranded RNAs were investigated during the 1970's for their anticancer effect. Some beneficial effects were noted, but severe toxicity (fever, liver toxicity and coagulation problems) limited their use. By creating the "mismatched" regions, Ampligen was able to deliver the same therapeutic effect without side effects. Laboratory tests on cancer cells showed that Ampligen was active against certain kinds of cancer and that it had a synergistic effect when administered with interferon (that is, the combination produced greater effects than either agent alone). Overall, 42% of the tumor specimens (including Kaposi's sarcoma) showed a greater than 50% reduction in tumor growth (4). Studies in mice also showed that Ampligen readily crosses the blood brain barrier (5). About 50 cancer patients have received Ampligen in various studies, resulting in mixed responses but no significant side effects. Cumulative doses up to 10 grams have been well tolerated, with only occasional mild, transient flu-like symp- toms. In a study of 3 patients with chronic myelogenous leukemia (CML) and 10 with renal cell (kidney) carcinoma combining Ampli- gen with interferon, all 3 CML patients achieved remission and 8 of 10 with kidney cancer demonstrated stable disease or partial response (6,7). Ampligen was also tested against 2 different strains of HIV and was found to significantly inhibit replication of the virus and to induce key enzymes that "chew up" foreign RNA, an impor- tant natural anti-viral mechanism in the body. As previously mentioned, Ampligen was shown to be synergistic with AZT (8). At present, the only method of administration being used for Ampli- gen is intravenous infusion, but animal studies have shown some activity with intranasal (inhaled) or subcutaneous (under the skin) injections, which would make long-term administration easier. Given all these theoretical advantages of using Ampligen in HIV infection, let us turn to the results of Ampligen treatment in people with AIDS and related conditions. Results seen with AIDS/ARC In the original Lancet report, the investigators said most ARC/LAS (lymphadenopathy syndrome) patients showed "immediate and striking clinical improvement." They gained energy and appetites; swollen lymph glands, liver and spleen returned to normal size, night sweats and thrush cleared up. All subjects received 200-250 mg of Ampligen twice a week intravenously. Treatment was interrupted in 2 patients, who voluntarily stopped the drug. However, fatigue recurred over 2-3 weeks and they returned for further therapy; within 1-2 weeks of resumption of Ampligen treatment, their symptoms again abated. Clinical improvement was less striking in the 3 patients with AIDS. The 2 with Kaposi's sarcoma had more energy, but their lesions either remained stable or slowly progressed. The third, whose immune system showed the most damage, died of a second bout of PCP after 7 weeks treatment. He had not been on PCP prophylaxis. The earliest immunologic change was the return of normal skin test responses ("delayed hypersensitivity" or DHR) in all 10 patients. However, DHR has not been established as a useful measurement of the state of the immune system in AIDS/ARC patients. The ARC/LAS patients recovered DHR after only a few doses, while those with AIDS required 8 to 12. T cell counts stabilized or gradually increased in all 10, but the improvements were minimal. Evidence of antiviral activity included reduction of HIV in 8 of the 10 by two or more tests. Viral culturing techniques, tests to show the numbers of infected cells, and levels of p24 protein all showed a progressive reduction, a very encouraging observation. Recent results The initial results reported in the Lancet are being borne out over the longer term, according to principal investigator David R. Strayer of Hahnemann University. Most of the original patients are still on Ampligen and 15 had been added as of mid- March, with duration of treatment now ranging to 16 months. Dr. Strayer says they can stabilize ARC patients and over time see stabilization or gradual increase in the number of T4 cells, with a corresponding decrease in HIV load measured by the techniques described above. Mean T cell increases, however, have been rather disappointing: 4% at 4 months, 8% at 8 months, and 17% at 12 months (9). The latest published results reported that 83% of ARC and 75% of AIDS patients had improved skin tests (DHR). In two thirds, swollen glands reduced, and most or all got relief from diarrhea, night sweats and fatigue. However, Ampligen treatment did not halt Kaposi's sarcoma in the AIDS patients (10). The ARC study A double-blind, placebo-controlled study of Ampligen has been underway for about 7 months in Atlanta, and recently two New York centers have been added (Metropolitan Hospital Center and St. Lukes/Roosevelt -- see Treatment Issues, Vol. 2 no. 1, p. 10). This study is expected to last 9 months, studying 300-350 ARC and LAS patients. In the Atlanta arm of the trial, 70 patients had been enrolled as of mid-March and followed for up to 7 months. According to principal investigator Dr. Jim Braude, exactly half believe they are getting Ampligen and not placebo, either because they are feeling better or because they feel a slight flushing after infusion (11). It must be emphasized that even Dr. Braude does not know who is getting Ampligen and who is getting placebo. He is seeing many patients improve, but not a dramatic 50-50 split: "Perhaps a quarter to a third are looking and feeling better." Increased energy is common, and cases of hairy leuko- plakia have resolved without other therapy. Dr. Braude emphasizes that there have been no toxic side effects in his study. A very preliminary glance at T cell data on 32 patients fol- lowed for 5 months show 12 higher than baseline and 20 lower, of which 4 are only slightly lower. The increases, however, have not been impressive, and we cannot compare Ampligen recipients to placebo recipients until the trial is completed and the "code" is broken. Also disappointing is the fact that, in this study to date, the measurements of viral activity (p24 levels) have not dropped dramatically. This is in direct contrast to the observa- tions in the pilot study. The reason for the unfortunate discrepancy is unclear, and it has prompted DuPont to perform a blinded interim analysis of the data to assess Ampligen's effec- tiveness and the ethics of continuing the study. The AIDS study In a separate, open label (non-placebo) trial, 60 patients with full-blown AIDS will be treated with 1 of 2 dose levels, either 200 mg or 400 mg twice weekly, of Ampligen. This trial is enrolling patients now in New York through the Community Research Initiative (212-463-8981) and in Atlanta through Dr. Braude, but his study is full. Patients whose clinical condition deteriorates during the study will be switched immediately to the higher dose of Ampligen; if they were at the higher dose, they will be escalated even further. Patients cannot take AZT during the study period but will be allowed to take aerosolized Pentami- dine for PCP prophylaxis and other necessary medications includ- ing Zovirax and anti-Toxoplasmosis medications, but cannot take AL721, Dextran sulfate, naltrexone or Antabuse. Women will be accepted in the trial, but must practice barrier contraception, because testing on rabbits indicates Ampligen may have an adverse effect on the fetus. Ampligen's future Asked about plans for future trials of Ampligen in combina- tion with other agents, Dr. Strayer said that Ampligen-AZT tri- als cannot be started until animal toxicity studies are complete. Some work has been done on Ampligen-interferon combinations, but no clinical trials are currently planned. At least one Ampligen trial is on the drawing board with the AIDS Clinical Trials Groups (ACTGs) at the NIH, but it probably will not be underway until the fall. Treatment Issues will be reporting on the status of these trials. Summary Ampligen is a promising antiviral and immunomodulating drug, based on the results seen with the patients described in the Lan- cet article. Preliminary results from the Atlanta ARC study, however, have been disenchanting in comparison. The reasons for this inconsistency are not clear and deserve swift scrutiny before large-scale trials begin. In the meanwhile, there is probably overall more encouraging data for Ampligen than for any other agent except AZT, which cer- tainly doesn't say much for the pace of AIDS research. All things considered, Ampligen deserves serious consideration, espe- cially by people who can't tolerate AZT. It may effectively buy more time until the "magic bullet" arrives. A point worth repeating: Ampligen, in the studies conducted so far, seems to have no appreciable effect on KS. The Immune System and GM-CSF, a Potential Boosting Therapy It is no fortuitous accident that people routinely avoid illness after exposure to the countless bacteria, viruses and protozoa teeming invisibly throughout the environment. A microscopic net- work of white blood cells and proteins sweeps our veins to rid the body of disease causing microorganisms, cancerous cells and other foreign substances. Study of this human cleansing mechan- ism, the immune system, has moved onto center stage in the arena of medical research over the last decade, largely in response to the AIDS epidemic. Three classes of white blood cells populate the immune sys- tem. Their common goal is to destroy anything that is recognized as non-self: pathogens (disease causing agents such as bacteria or viruses) and environmental debris like pollen, smoke, etc. Foreign substances are referred to generically as antigens, a class which includes anything capable of stimulating an immune response or causing an allergic reaction, the consequence of an overly zealous immune response. A well functioning immune system accomplishes its task in four waves: recognition of "non-self", mobilization of the appropriate defenses, attack and finally, slowdown of the coordinated response. To understand how HIV short circuits the exquisitely subtle protection provided by our immune system, it is necessary to be familiar with the key players and how they interact. Blood cells are born in the bone marrow, which churns out generic "pluripotential" stem cells. These adolescent cells are modified by various growth factors (hormones) circulating in the blood and can mature into one of the several specialized com- ponent cells of the immune system. A hardy class of white blood cells known as phagocytes elim- inates foreign substances by engulfing them and destroying them with enzymes. These "pac-man" cells are not particular; they will ingest just about any kind of debris they encounter, includ- ing damaged or dying cells. The most prominent of these cells is the macrophage. Usually the first to arrive at an infection site, macrophages approach and swallow foreign particles. However, they are not capable of killing the invader alone; they need the assistance of the specialized T4 cell, which they summon and "introduce" to the enemy. Together, macrophages and T4s demon- strate cell-mediated immunity in a partnership that will be described later on. As well as directly engaging foreign substances, macrophages and other similar cells are responsible for inducing fever and inflammatory responses. These reactions are stimulated by release of a monokine (an enzyme secreted by mononuclear cells) called Interleukin-1, one of approximately 100 secretions pro- duced by activated macrophages. Immature stem cells differentiate into one of two brands of lymphocytes, white blood cells that recognize and destroy specific antigens. Cells that follow the route to become B lym- phocytes form the backbone of the humoral immune system. B cells produce antibodies in the lymph nodes. When the body encounters a foreign substance for the first time, the contact may lead to synthesis of antibodies, which is an example of acquired immunity. Antibodies attack proteins or other antigens that are potentially harmful to the body by binding to the antigen and "flagging" it as foreign. Actual elimination of the antigen may be accomplished by another phagocytic cell. The other variety of lymphocytes continues the maturation process in the thymus gland, and they are therefore known as "T" cells. By secreting a whole host of substances known as lymphokines, T cells orchestrate the movement of many of the other white blood cells. Secretion of these lymphokines is deficient in AIDS, and several of them e.g. Interferon and Interleukin 1 and 2, are being investigated as potential therapies. In their role as coordinators of an immune response, T cells perform a critical function. T4 cells, also known as T helpers, are equipped with recep- tors that fuse with specific antigens. T4s normally work in tan- dem with macrophages. When summoned to the site of an infection by a macrophage, the appropriate T4 fits its receptor over the protruding antigen presented by the macrophage, much like a lock and key mechanism. In this way, the T4 "recognizes" the enemy. Once activated, the T4 reproduces and secretes its potent lym- phokines. These substances convey messages to the other com- ponents of the immune system stimulating B cell production of antibodies, signaling another class of T lymphocytes called Natural Killer, or cytotoxic T cells, and calling other macro- phages to the site of infection. Natural Killer cells directly attack tumors and virally infected cells, rupturing their outer membrane. Currently, it is not understood why these cells are not effective against cells infected with HIV. The final stage of an immune response is relaxation to a normal state. The control switch is operated by T8 or T Suppressor cells. These lympho- cytes are sensitive to high concentrations of circulating lym- phokines. T8s release their own lymphokines when an immune response has achieved its goal, signaling the other participants to cease their coordinated attack. If the response involved a substance encountered for the first time, a number of "memory" B and T lymphocytes will remain in circulation. Reinfection will be met with a swifter, stronger reaction from a prepared reserve of white blood cells. A healthy immune system is comprised of twice as many T4 cells as T8. In someone infected with HIV, however, this ratio often reverses. HIV distinguishes itself by specifically infect- ing one kind of cell, the crucial T4. The virus enters T4s through the characteristic protein that acts as a receptor. Infected T4s do not necessarily die; therefore, detectable T cells may actually be dysfunctional, clouding the significance of T cell measurement. The virus also encodes its genetic informa- tion into the host cell's DNA, thereby insuring its own survival and reproduction. HIV inhibits T4 growth, and indirectly affects the rest of the immune system. T4s are rendered incapable of secreting lymphokines and cannot signal B cells to produce anti- bodies or call in Natural Killer cells. They can no longer aid macrophages in destroying invaders. Infected T4s also secrete a substance known as "soluble suppressor factor", which inhibits T cell dependent immune functions, even in uninfected cells. In addition, healthy T4s perceive infected cells as "non-self", and attack them. Upon contact, HIV travels to the previously healthy cell, securing another foothold in its methodical campaign to shut down the immune system. The steady depletion of T4s eventually results in a converse proportion of T4s to T8 cells. The flurry of activity in response to HIV infection leaves high levels of lymphokines in the bloodstream. T8s respond to this state, as ususal, and move to dampen the immune response. The stage is set for infectious agents that are normally repressed, such as pneumocystis carinii, to proliferate unhindered and to cause disease. GM-CSF In the search for AIDS therapies, there have been two main focuses: antiviral drugs against HIV and drugs designed to enhance the immune system. A new drug, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), has been shown to increase the number of certain kinds of white blood cells and may turn out to be an important immune enhancer in AIDS. While it has not impressively stimulated production of the key T4 cell, it does effectively spur the development of neutrophils (phagocytic cells), which are the white blood cells hardest hit by AZT. Therefore, it may prove to be most useful as a therapy for those on AZT whose white blood cell count has been depressed by this antiviral. It may also be useful in conjunction with chemoth- erapy, which can also depress white cell counts (12). GM-CSF has recently been synthesized and is being used in clinical trials in an attempt to induce production of certain white blood cells. It has been discovered that GM-CSF may protect bone marrow and stimulate production of the so-called myeloid cells (neutro- phils, eosinophils, red cells and platelets). Clinical trials are underway in Boston, Tucson, Los Angeles, and most recently, New York with GM-CSF, which may also amplify the ability of phagocytic cells to rid the body of foreign substances. Dr. Jerome Groopman, affiliated with the New England Deaconess Hospi- tal in Boston, has administered GM-CSF to 16 AIDS patients (13). Patients received an initial IV dose of the drug, and 48 hours later began a 14 day continuous IV infusion at five different dosings. Increases in circulating neutrophils, eosinophils and monocytes were seen, in proportion to the dose administered, but these levels dropped to base-line within 3-9 days after the infu- sion was stopped. High doses of GM-CSF were well tolerated by patients; minor side effects included mild aches, chills and fever. The flulike symptoms may have resulted from the release of fever causing proteins by white blood cells fighting infec- tion. Four patients also experienced phlebitis and inflammation of the veins. One patient requested early cessation of treatment (day 13) due to muscle pains, decreased energy and diarrhea. These symptoms soon resolved (14). It is felt that eventually GM-CSF may not have to be given intravenously but might be effec- tive as a subcutaneous injection, like insulin, at daily or even weekly doses. Production of T helper cells was also stimulated in some patients, although these changes were small, and the ratio of T helpers to T suppressors was not affected. Whether or not a higher absolute number of T helpers is beneficial is open to question; some investigators feel that more T helpers will merely provide additional vehicles for HIV to proliferate throughout body. Groopman is starting a study combining GM-CSF, AZT and erythropoietin, a substance that stimulates red cell production. This trial will examine the mechanism by which GM-CSF may possi- bly increase absolute T cell counts. Some important shortcomings of GM-CSF should be noted. These hormones do nothing to restore normal functioning of T helper cells, which is a key concern in AIDS. Its ability to sustain higher levels of the phagocytic cells seems limited and the drug may be needed indefinitely. Also, Dr. Anthony Fauci found that GM-CSF actually spurred on HIV replication, (15) a sharp contrast to Groopman's findings. However, Groopman states that there is no evidence that GM-CSF has encouraged multipli- cation of HIV in the patients he has treated so far (16). Dr. Groopman plans to study GM-CSF in combination with AZT and antibiotics in patients with mycobacterium avium infections, a form of tuberculosis frequently seen in AIDS. This study will explore the possibility of protecting the bone marrow from AZT's toxic assault on the body's blood cell factory. Dr. Susan Krown is the chief investigator of the trial exa- mining GM-CSF with AZT planned at Memorial Sloane-Kettering. Details of the trial were not available when this issue went to print. Dr. Krown can be reached at 794-7426. Dr. Groopman's assistant, Dr. DeLeo, can be reached at (617) 732-8560. More on Dextran and More on the NIH At the recent meeting of the NIH-sponsored AIDS Clinical Trials Groups (ACTG) in Bethesda, there appeared to be a mysteri- ous about-face regarding Dextran. Last December, hopes were high for this drug, based on Dextran's good antiviral activity in the test tube (17). These results have since been confirmed by several groups (18,19). As a result, Dextran was quickly assigned a "high priority" status by federal researchers. Despite this apparent red carpet treatment, no clinical trials have been initiated, and in fact, it appears that Dextran will be caught up in red tape until July when the ACTGs next meet. Why has such a promising and widely used drug gotten stalled at the gate? Background Let's review how a drug goes from the test tube to a clini- cal trial at the NIH (for more detailed background information, see Treatment Issues, Vol. 2 no. 1: "Your Tax Dollars at Work: The NIH AIDS Effort"). Potential AIDS drugs (which are brought to the attention of the NIH either by pharmaceutical companies or by private researchers) are screened and assigned research prior- ity by a very influential body called the AIDS Clinical Drug Development Committee (ACDDC). The ACDDC is a group of 20 "experts in infectious disease, virology, immunology and oncol- ogy" who review the available data on various drugs and assign a research priority: low, medium, or high. Investigators desiring to conduct a study of a particular drug submit "concept sheets" which are reviewed at the quarterly general meetings of the ACTGs. Concept sheets are discussed and commented on at these meetings. Then, a rather mysterious decision-making process occurs, and wheels are set in motion to transform selected con- cept sheets into clinical trials. Clearly, concept sheets for "high priority" drugs will most likely get approval, but as NIH researchers are quick to point out, some "low priority" drugs (like AL721) have eventually come to clinical trials. In most cases, however, this seems to be more a result of public pressure than real NIH interest. Dextran's "high priority" status combined with investigator interest (at least one concept sheet was submitted for Dextran) should have been enough to get a rapid pilot study going after the December meeting. That didn't happen. In March, the Primary Infection and Pharmacology Committees (both deal with antiviral drugs) became cool and disinterested in Dextran. Their reasons were not made clear, although something was mentioned about need- ing more data on absorption and tissue distribution. Suddenly a drug that generated great interest three months earlier was uni- laterally scrapped without satisfactory explanation. This is most distressing, and seems to be out of sync with other recently-introduced policies, including the desire for an increased public disclosure regarding internal NIH decisions. Implications For the users of Dextran sulfate, indeed for the AIDS com- munity in general, an all-too-familiar situation arises: a promising non-toxic substance surfaces as a potential AIDS therapy. It is readily available and thereby captures the atten- tion of the AIDS community. It is in the "window of opportunity" that the NIH has aptly described as the point in time when a drug must be investigated, before it is in such widespread use that a good clinical trial is difficult or impossible. As has often been the case in dealing with AIDS drugs, the "window of oppor- tunity" for Dextran has been missed by the very people who coined the term. Valuable data is being lost. We are left ourselves to determine Dextran's worth through our own anecdotal observations; unfortunately, little useful data has accumulated (or is likely to accumulate) since our last report. Over a two to three month observation period, New York physicians have not seen striking clinical benefit or increases in T-cells, but this may be too short a period to make definitive statements. The necessary tests to determine antiviral effect (p24 levels, viral culturing, etc.) are not available to community-based physicians, so we are not able to make this key assessment for Dextran. The San Francisco General Hospital study is following people in whom an antiviral effect cannot be demonstrated. All but one are p24 antigen negative which presumably means HIV is dormant in this group. The only useful data that we will likely obtain from the San Francisco study concerns the low level of toxicity, and this was already reported in Treatment Issues (Vol. 2 no. 2). Therefore, no informed recommendations can be made regarding Dex- tran, and it is unlikely that any authoritative data will be forthcoming. The mismanagement of Dextran by the NIH certainly has a sobering effect on our enthusiasm with the new procedures and policies implemented last December. Designed to "encourage investigator innovation", increase public disclosure, and leave no stone unturned in the fight against AIDS, one may well wonder if they are mere window dressing on the same bureaucratic system that has been in place for years. Other NIH developments As for updates on ongoing studies, little new data was presented. Two key studies, the half-dose AZT study and the AZT plus acyclovir study, will be not reported on until June at the International Conference in Stockholm. Also, early studies of AZT plus interferon for Kaposi's sarcoma will be presented at that time. Many ideas ("concept sheets") were proposed for future tri- als. They included: 1. A large-scale trial with alternating therapy of AZT and ddC; 2. A larger trial of the AZT/acyclovir (Zovirax) combination; 3. Continuing studies of the AZT/interferon combination in a wider group of ARC and AIDS patients; 4. A small trial of the CD4 protein; 5. Trials combining GM-CSF (Granulocyte Macrophage Colony Stimu- lating Factor) with AZT; 6. A multiple-dose study of Ampligen; 7. Studies of the forgotten immunomodulators AS101 and Isoprino- sine; 8. Studies of Ribavirin in asymptomatic seropositives, ARC and AIDS patients. Remember, these "concept sheets" are proposed studies and must meet the approval of the various scientific committees at NIH before they can get underway. The concept sheets selected to go into trials will be announced at the July meeting. Finally, an important outcome of the March meeting was the long-awaited recognition that withholding PCP prophylaxis from ARC/AIDS patients enrolled in clinical trials is unethical. All forthcoming trials (and some current trials) will allow aerosol- ized pentamidine for PCP prophylaxis. We applaud this decision. New Studies Researchers at Cabrini Medical Center are conducting a trial of the immunomodulator drug Thymopentin in patients who are HIV Positive but who do not have AIDS. The trial, which will last 24 weeks, is double blind, and half will receive placebo. Patients must be HIV Positive and have T-cells greater than 200. Prior studies with Thymopentin in children with full-blown AIDS were disappointing, showing only transient clinical and immunologic improvement. Similarly, Thymopentin treatment in adult AIDS has been disappointing, although this may be because the treatment was given too late when there were not enough T-cells to stimu- late. There is, therefore, a good rationale for studying Thymo- pentin in earlier stages of HIV infection. A placebo-controlled study of such short duration in asymptomatic individuals seems ethical. No side-effects have been observed during Thymopentin treatment. Interested physicians may call Alfred Giosa, RN at (212) 995-6872. In Brief The San Francisco Department of Public Health has prepared some excellent pamphlets dealing with Nutrition and AIDS, includ- ing tips on food preparation, boosting calories and protein, and improving food intake. Contact the Public Health Nutritionist, San Francisco Department of Public Health, 101 Grove St. Room 118, San Francisco, CA 94102 or phone (415) 554-2572. The World's Fair Pharmacy & Surgical Supply Co. has recently announced extended professional services to PWAs. Besides accepting as payment-in-full the amount paid by insurance com- panies, they will accept a "Temporary Medicaid Authorization" form and ADAP (New York State AIDS Drug Assistance Program). They will also dilute pentamidine into individual vials for aerosol- ized use. Prices are competitive and delivery free to PWAs regardless of where they live. For a full description of services, contact them at (718) 358-1300. Corrections Mogus Availability Despite earlier statements to Treatment Issues, Vince LaRocca informed us that he does not sell WoBe-Mogus enzymes directly to the public. The enzymes are available from two dis- tributors in New York City: Willner Chemists, 330 Lexington Ave., (212) 685-0448 and The Vitamin Shop, which has 9 locations in Manhattan, (201) 866-7711. Willner has the enzymes on the shelf and charges less than The Vitamin Shop, which will ship it upon order from the warehouse in New Jersey. Make sure to ask for Polyzym 021 and Polyzym 023. AL-721 and AZT Studies In our New Studies section last month, we reported two clin- ical trials being conducted at Memorial Sloane-Kettering and Beth Israel Medical Center. Contrary to what we printed, the AZT study for asymptomatic seropositives is recruiting candidates with a T4 count of greater than 500. Also, the AL-721 study is open to patients with Persistent Generalized Lymphadenopathy or other ARC symptoms and a T4 count of less than 200. More infor- mation about either of these studies is available from Cynthia Vassallo, RN or Delia Brown, RN at (212) 794-7164. Dr. Donna Mildvan is coordinating the same AL-721 study at Beth Israel: (212) 420-4005. We apologize for any confusion resulting from these inaccuracies. Treatment Issues is GMHC's newsletter devoted to experimental AIDS therapies. Describing an experimental therapy should not be construed as recommending it. All new treatments should be done under a physician's care. Treatment Issues is published ten times yearly. Copyright 1988 Gay Men's Health Crisis, Inc. All rights reserved. Non-commercial reproduction is encouraged. Subscription lists are kept confidential. Editor: Barry Gingell, M. D. Associate Editor: Kevin Armington GMHC, Department of Medical Information, 132 West 24th Street, Box 274, New York, NY 10011 Footnotes: 1 Carter WA et al. Clinical, immunological and virological effects of Ampligen, a mismatched, double-stranded RNA, in patients with AIDS or AIDS-related complex. The Lancet: 1887, 6/6/87. 2 Strayer DR. Personal communication. 3 Greene JJ et al. Chapter 26: Therapeutic applications of double-stranded RNAs, in: Interferons and Their Applications, Came PE and Carter WA, eds. New York, Springer Verlag, 1984, p. 535. 4 Strayer DR et al. Antiproliferative effect of mismatched double-stranded RNA on fresh human tumor cells analyzed in a clo- nogenic assay. J Interferon Res 6: 373, 1986. 5 Hearl WG et al. A misaligned, double-stranded RNA, poly (I): poly(C12U) induces accumulation of 2',5'-oligoadenylates in mouse tissues. Biochem Biophys Res Commun 138: 40, 1986. 6 Strayer DR et al. Complete clinical responses in solid tumor patients without side effects or toxicity using mismatched double-stranded RNA (Ampligen), abstract 943. ASCO Proc 6: 240, 1987. 7 Carter WA et al. A phase I-II study of mismatched double- stranded RNA (Ampligen) in combination with interferon-a(Le), abstract 1513. AACR Proc 28: 382, 1987. 8 Mitchell WM et al. Mismatched double-stranded RNA (Ampligen) reduced concentration of AZT required for in vitro inhibition of HIV. The Lancet: 890, 4/18/87. 9 Strayer DR. Personal communication. 10 Strayer DR et al. HIV-related immune dysfunction: clinical improvement and immunological/virological effects of Ampligen therapy, abstract 363. Blood 70(5 suppl 1): 127a, 1987. 11 Braude J. Personal communication. 12 Brandt SJ et al. Effect of recombinant human granulocyte- macrophage colong-stimulating factor on hematopoeitic reconstitu- tion after high-dose chemotherapy and autologous bone marrow transplantation. NEJM 318(14): 869, 1988. 13 Groopman, JE et al. Effect of recombinant human granulocyte- macrophage colony stimulating factor on myelopliesis in the acquired immunodeficiency syndrome, NEJM 317 (10): 593, 1987. 14 Groopman J. Personal communication. 15 Folks TM et al. Cytokine-induced expression of HIV-1 in a chronically infected promonocte cell line. Science 238: 800, 1987. 16 Groopman J. Personal communication. 17 Ueno R et al. Dextran sulphate, a potent anti-HIV agent in vitro having synergism with zidovudine. The Lancet: 1379, 6/13/87. 18 Ito M et al. Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro. Antiviral Res 7(6): 361, 1987. 19 Nakashima H et al. Sulfation of polysaccharides generates potent and selective inhibitors of human immunodeficiency virus infection and replication in vitro. Japan Jour Canc 78(11): 1164, 1987. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display