&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& Copyright 1992 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #165, December 18, 1992 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: [items are separated by "*****" for this display] Passive Hyperimmune Therapy: Data Leaves Questions Unanswered Acyclovir Annual Price Cap for Some Patients, $2500; Registration Required Reform of Federal AIDS Research Proposed to New Administration, Congress New Software Available for Physicians' Offices and Community- Based Research AIDS TREATMENT NEWS Selected Index Through 1992 ***** Passive Hyperimmune Therapy: Unanswered Questions by Dave Gilden In October the HemaCare Corporation of Los Angeles announced preliminary analysis of its completed 12-month phase I/II trial of passive hyperimmune therapy (PHT, also known as passive immunotherapy or PATH). The blood products company claimed, in its statement and presentation at the National AIDS Update Conference in San Francisco, that the data confirm earlier indications of benefit (see AIDS TREATMENT NEWS #148, April 3, 1992). AIDS TREATMENT NEWS recently obtained from independent sources an unreleased, detailed statistical analysis of the trial data, performed by members of the University of California Los Angeles Department of Biomathematics. That report raises questions about the completeness of HemaCare's summary description of the data collected so far. Conclusions about PHT's long-term therapeutic value must await the findings of planned two-year phase III studies. PHT aims to restore people's ability to control their HIV infections after immune deficiency has set in. Patients receive monthly infusions of blood plasma pooled from asymptomatic HIV- positive individuals who are continuing to produce high levels of anti-HIV antibodies. The data released by the company in October seemed promising. After a year on full dose PHT, volunteers who started with T-helper counts of 50 to 200 experienced an average T- helper cell loss of two per cent, compared to a 35 per cent reduction for those on placebo. The benefit from PHT appeared to be dose-related: Volunteers receiving half dose fell between the two values, with an average 25 percent T-helper cell loss. Five deaths occurred on the placebo arm, three on the half-strength arm and one on the full-strength arm. The company reported no significant adverse affects from the therapy, and no withdrawals because of toxicity. While not questioning PHT's safety, the full statistical analysis presents a more confused picture than do the sketchy press releases. Most of the trial volunteers yielding usable data -- 93 out of 155 -- had T-helper cell counts of less than 50. No significant benefits to volunteers with such low counts were detected. This result conforms to a past study by Abraham Karpas, Sc.D., of the University of Cambridge. Dr. Karpas' small study observed that the benefits of passive immunotherapy for people with people with ARC were much more long-lasting than for people with AIDS. [See Proceedings of the National Academy of Sciences, USA, volume 67, October 1990, pages 7613-7617). Joshua Levy, M. D., HemaCare's research director, told AIDS TREATMENT NEWS that the decision to focus on people with depleted T-helper populations was based on reasons of compassion as well as a desire to quickly obtain decisive data. The positive findings HemaCare reported are based on 62 individuals with T-helper counts of 50 to 200. This small sample size reduced the possibility of obtaining clear-cut, statistically significant findings. The full statistical analysis shows that average T-helper counts in the 50 to 200 segment of the trial did jump upward in the first six months. But the one-year data are not as good: T-helper counts on full dose in this group, up 33.7 percent above baseline at six months, had fallen back essentially to baseline by one year. The trend in the second six months raises the question of how well PHT preserves T-helper cells in the long run. An analysis carried out by the statisticians that gave greater weight to later T-helper counts revealed little significant treatment effect compared to the simple endpoint analysis HemaCare publicized. As for survival rates, only a trend considered largely lacking in statistical significance was found when other factors were taken into consideration along with T-helper count. These factors included AIDS or ARC diagnosis, weight loss and baseline p24 antigen level. An unexpected problem is that original T-helper counts are missing for 29 of the 203 volunteers in the trial as a whole. In the full-dose PHT arm, the baseline T-helper counts are unknown for 5 of the 17 deaths. This gap might have seriously skewed the results; adding just one more death to the full-dose, 50-to-200 helper T-helper segment of the trial would alter the announced results considerably. To get an independent view of PHT, we spoke with a staff member at one large AIDS clinic that is treating 30 patients with a passive immune technique similar in principle to PHT. According to this source, T-helper counts have not generally risen in treated patients, although skin conditions of all sorts have markedly improved. This benefit could be due to other antibodies in the plasma as well as to the anti-HIV ones, the source observed. He noted that enthusiasm for the therapy was waning at his clinic. As was largely true in the HemaCare study, passive immunotherapy is being applied in this clinic as a rescue technique for people with T-helper counts under 50. It is unclear what kills T-helper cells at this stage of disease. Their further loss may not be due to current HIV activity at all, but to immune dysfunction springing from past infection. Also, HIV in advanced AIDS is reproducing rapidly and therefore can mutate to escape neutralization by particular antibodies. It would seem that passive immunotherapy's effectiveness would be limited under these conditions. Michael Roth, M. D., is a Santa Monica immunologist who has had six years experience administering passive immunotherapy in his AIDS practice. He thinks that the critical factor determining passive immunotherapy's effectiveness is clinical health. Some patients who have near-zero T-helper counts but no history of opportunistic infections have remained stable and in good health for years on passive immunotherapy, he told AIDS TREATMENT NEWS. Drs. Roth and Karpas both think that PHT and similar therapies would be most useful for extending the asymptomatic period by several years in persons with moderately affected immunity (T-helper counts of 200 to 400). But it is difficult to test PHT's effectiveness in this group because of its members slow rate of decline. HemaCare is now seeking a "treatment IND" from California's Food and Drug Branch (a state equivalent of the FDA) to try PHT in people with T-helper counts in the 200 to 400 range. The two-year, open- label treatment IND will allow HemaCare to administer PHT and collect data at its four California infusion centers. HemaCare also will attempt to recover costs from patients' insurance companies. (The company does envision some free distribution to those unable to pay.) Meanwhile, a double-blind, two-year-long phase III trial involving volunteers with T-helper counts of 50 to 200 will begin this winter if the FDB approves. Over 100 volunteers from the phase II trial will continue to receive PHT. This is important because one small French study indicated that discontinuing this therapy led to rapid deterioration in people with advanced immune deficiency. [D. Vittecoq et al., Journal of Infectious Diseases, Feb. 1992, 165(2):364-8] HemaCare expects to be administering PHT to 900 people soon and is actively seeking donors with sufficient HIV-neutralizing antibodies. Donors receive $25 per donation plus free blood tests. A beneficial rebound effect from the periodic plasma withdrawals may raise donors' antibody levels, indirectly making passive immunotherapy of benefit to them, too. In the completed HemaCare trial, about 90 per cent of regular donors maintained stable T-helper levels over the year. According to HemaCare, donor data revealed a statistically significant, overall slight T-helper increase when analyzed by a method that controlled for other factors. The meaning of such a result should be qualified, though, since there is no control group for purposes of comparison. It is possible that any carefully selected group of individuals with high anti-HIV antibody levels would spontaneously show stable or even increasing T-helper counts whether or not they donated plasma. Comment Tanya Youvan, M. S., HemaCare's PHT project manager, faxed us a five-page letter taking exception to some of the statements in a draft of this article. She wrote that HemaCare has hired a new statistician to redo the analysis. His report is due soon and, Ms. Youvan claimed, will provide most of the missing baseline T-helper counts. Ms. Youvan also argued that the just- completed PHT trial was only a phase I/II study that was not supposed to provide conclusive efficacy data. We welcome re-examination of the PHT data and further testing of this therapy. But people with HIV are now making decisions about trying PHT and they need as much information as possible. HemaCare's overly optimistic announcements of its trial results were made two months ago. They claimed improved survival and statistically significant maintenance of T-helper cell levels on the basis of an analysis the company now feels it has to redo. Ms. Youvan's objections did not touch two central points: (1) Average T-helper cell counts were not "maintained," but rose in the first six months and then starting falling. By the end of the 12 month period, they were about equal to baseline in the 50-200 T-helper group, suggesting that T-helper count increases may be temporary. (2) The missing baseline helper T-cell data make the survival findings uncertain. Ms. Youvan conceded that firm conclusions about who PHT benefits, and for how long, must wait for the larger study now being planned. But we should not be too critical of the optimistic publicity HemaCare generated. The blood-products company has taken on a very complex, neglected project beyond its normal area of expertise. The need for prolonged testing has proved extremely costly to the company, which has had to cover the testing expenses through internal financing. The focus on persons with low T-helper counts may have backfired, costing the company more in the long run. It nevertheless was a valiant move on moral grounds. It provided a plausible treatment alternative to people who had none, as most clinical trials exclude people with late-stage AIDS. HemaCare in the past has been faulted for releasing its results through press conferences and other non-research forums (such as the National AIDS Update Conference). It now promises to submit its findings in a peer-reviewed medical journal for publication -- which would help to resolve the remaining questions. ***** Acyclovir Annual Price Cap for Some Patients, $2500; Registration Required by John S. James On December 7, Burroughs Wellcome Co. announced that it will cap the price of acyclovir (Zovirax) for patients who pay for the drug themselves. Those who use more than 730 grams (for which Burroughs Wellcome charges wholesalers about $2500) in a single calendar year will receive up to 730 grams additional at no cost for the remainder of the year. This program begins January 1; therefore patients who are using continuous high-dose acyclovir and paying for their own medication should immediately register, through their physician or other health-care provider, so that their acyclovir use can be monitored and credited toward the cap. Health-care professionals can call Burroughs Wellcome at 800/722-9294 for more information about this program and how to register patients. Unfortunately this program is only for patients who do not have third-party coverage for their acyclovir use. The cost of acyclovir has become an issue, especially during the last year, because more people are using high doses continuously after a major study in Europe and Australia reported finding survival benefit in some patients. (Youle, M. Double blind, placebo controlled trial of high dose acyclovir for the prevention of cytomegalovirus (CMV) disease in late stage HIV disease. VIII International Conference on AIDS, Amsterdam July 19-24, presentation number MoB 0056.) Most patients use acyclovir occasionally or temporarily. But the new use can cost $5000 per year or more, creating severe financial hardship or making the drug unavailable to patients for whom it was prescribed. The U. S. patent on acyclovir does not expire until 1997. AIDS treatment activists from several organizations had negotiated with Burroughs Wellcome for ten months seeking price relief; according to Andrew Zysman, M. D., of ACT UP/Golden Gate, the company rejected an overall price cut but agreed to a price cap. Activists were not told the amount of the cap, or that patients with third-party coverage for the drug were ineligible, until the day the program was announced to the press, so they were unable to advocate for important changes. "There are two problems with the policy," said Dr. Zysman. "The cap, while a start, does not go far enough. A workable solution would be an annual cap of $2000 per patient, which would continue to generate great profits, while making acyclovir more accessible. "Second and most disappointing, the cap only applies to people without insurance. Activists are concerned about the cost of AIDS care not only to uninsured individuals, but also to the bankrollers of health care in America, the government and private insurers. Many physicians, for example in public health settings, are unable to suggest the use of acyclovir because it would bankrupt their clinic's budget; hence patients will not be able to benefit. "We believe Burroughs Wellcome has made a grave error, acting neither in its own interests nor in the interests of the HIV community. A lower price cap, applied to all patients irrespective of insurance coverage, would affect physicians' attitudes about the cost-benefit ratio of acyclovir, and would create more widespread usage, generating greater, not lesser profits for Burroughs Wellcome." Dr. Zysman has heard that Burroughs Wellcome did plan for the cap to cover all U. S. patients, but that pharmacists' representatives argued that their prescription-monitoring software was not set up to track such use. He also heard that activists were kept out of these negotiations because the company feared running afoul of regulations on the disclosure of "inside information" which could affect stock prices. Note: Burroughs Wellcome replied that it already provides a 26 percent rebate to Medicaid, and effective January 1 will provide comparable discounts to state AIDS programs, sexually transmitted disease clinics, community and migrant health centers, homeless programs, public housing clinics, and mental health, tuberculosis, and family planning clinics. ***** Reform of Federal AIDS Research Proposed to New Administration, Congress by Keith Griffith A reform package that could lead to significant changes in the way the federal government conducts AIDS research at the U. S. National Institutes of Health is being given serious attention by the Clinton transition team. The reforms, which are still being developed before the convening of a new Congress in January, are viewed by proponents as critical if President-elect Clinton is to live up to his campaign rhetoric for a vastly more serious commitment to AIDS. AIDS TREATMENT NEWS has learned that representatives from Treatment Action Group (TAG), AIDS Action Council (AAC), and Human Rights Campaign Fund (HRCF) have conducted high level meetings at NIH regarding the reform package. These groups have also found significant support both on Capitol Hill and in the Clinton transition team. The reform package, actually a series of 24 proposals, would centralize all AIDS research programs at NIH under the authority of the Office of AIDS Research (OAR). "We want the OAR to have increased budgetary and administrative authority," TAG representative Gregg Gonsalves stated. "Right now there are 21 institutes, centers and divisions at NIH that supervise AIDS research, and we would like OAR to have a single budget line for themselves and to distribute money instead of going through 21 directors who decide where it goes. [The AIDS program at NIH] is a huge program, $1.2 billion. If that were reorganized well, run more efficiently, with some sort of strategic vision for what they were doing, we would have reason for hope." Gonsalves speaks confidently about the need to centralize AIDS research at NIH because earlier this year he and colleague Mark Harrington, both of TAG, conducted an exhaustive study of the NIH AIDS program (see AIDS TREATMENT NEWS issue # 156). What they found was a billion dollar investment with no one in clear command. In the study by Gonsalves and Harrington, they documented what many have suspected all along: that NIH is plagued by gaps in research, that redundancy is far too common and that there is virtually no strategic planning. OAR, which was created by Congress in 1988 to oversee federal research at NIH, was never given enforcement powers to carry out its mission. The TAG report calls it all "an elaborate charade." "OAR has no teeth at all," is the belief of Derek Hodel of AAC. "The reforms we are circulating are designed to give OAR the teeth to do the job they were mandated to do in the first place: to coordinate AIDS research, to devise a strategic plan with broad research goals, and to coordinate research among the NIH institutes." This would be accomplished by giving one office, the OAR Director, authority to oversee budget decisions and enforce both short and long-term planning. OAR would report directly to the NIH Director and would work with the newly created Special Assistant to the President on AIDS (frequently referred to as "AIDS Czar") to assure a continued pro-active stance from the White House. Will These Reforms Work? The critical question, we think, is whether these reforms would actually make a significant enough improvement in the development of meaningful treatments, a cure for persons living with HIV today, and eventually a vaccine. Additionally, many scientists will wonder how these reforms will impact on them. There has been little community discussion over these reforms recently since very few people are aware just how seriously they are being taken, now that the Bush Administration is on the way out. This lack of public discourse is not because of some desire to hide these proposals. It reflects the sad state of affairs regarding how few people are advocates for treatment research within the network of community-based organizations which deal primarily in AIDS care giving and prevention. Nevertheless support is growing and supporters on Capitol Hill may place the reforms into legislation as early as January. Senator Ted Kennedy and Congressman Henry Waxman are expected to include the package in bills that will also remove the ban on fetal tissue research and strengthen women's health research funding. AIDS TREATMENT NEWS, looking to find expert opinion about whether this particular reform package could succeed in improving research at NIH, spoke at length with a senior professor at one of the nations most respected schools of public health. This person, who did not wish to be identified, has significant experience working within large institutions engaged in protecting the public health. Our source has had little experience in the field of AIDS research and was relatively unaware of the current situation at NIH. After studying the reform package, we went through each proposal separately. Concern was voiced only around issues of how some points would not likely be acceptable to a bureaucracy or to existing government hierarchies. There was concern that the OAR Director would be in a position of advocating publicly against the policy of the Administration. Another concern was voiced about the implications of creating a budget bypass (allowing OAR to report directly to the president on budgetary issues, rather than going through NIH; the National Cancer Institute at NIH has had a similar bypass since 1972), though there was agreement that oversight and enforcement of a budget would work better if direction comes from one office. Even with these reservations, our expert source stated, "The idea of having an (OAR Director) who is in charge of coordinating across all the institutes and having a lead role in running various task forces, not only within the Public Health Service, but also outside, would be very healthy and helpful and I think ought to be possible." Those pushing these reforms are in the process of winning scientific support, as well as seeking out diverse views about how to strengthen the existing package. A large list of names, both in AIDS research and in other areas, has been assembled and will be consulted in the coming weeks. Derek Hodel with AAC worries that some scientists might see these reform efforts as a way to interfere with what researchers can do in the lab. "I don't think that our plan would impede the kind of creative thinking needed to fight AIDS," Hodel said. "The types of direction we are looking for are very broad, thematic directions." The reform package is coupled with a push for a fifty percent increase in federal spending on AIDS research in 1993. Activists believe the two together will provide the significant jolt needed to open up the pipeline to new research and speed along projects already in development. Another crucial part of the strategy, being developed jointly by TAG, AAC, HRCF and others, will be obtaining the president's support. One document, "Confronting HIV/AIDS: Initiating Change," a 24 page outline of what is needed from the new Administration, which came out of a recent meeting of 75 community leaders convened by AAC, calls upon President-elect Clinton to deliver a major televised address to the nation on AIDS during the first 100 days of his Administration. Hodel described what the President should do in such a national address, to add the sense of urgency needed as well as reforming NIH and providing additional funding. "It is hard to know for sure, because we have never had presidential leadership, but I think in the case of AIDS, a signal from the President would do it. If the President tells NIH, 'move this stuff,' it will happen. President Clinton needs to say that AIDS research is a top-priority of this administration. It needs to be that clean and that simple and that public a signal." ***** New Software Available for Physicians' Offices and Community-Based Research by John S. James A medical-office and research software system, developed over the last five years by the nonprofit National Community Research Initiative (NCRI) in Washington, D. C., is now available for community-based research organizations and for medical- records management in physicians' offices and clinics. The system, called Medsys*, is remarkably easy to use; it largely automates the maintenance of patients' charts, produces custom patient flowsheets on demand, and assists in other functions including prescriptions, laboratory, specialists and referrals, and scheduling. In addition to its use in daily clinic management, the system supports research in several ways. It keeps almost all patient data in a compatible, computerized form, so that records can be combined from different practices and clinics for retrospective studies. It enables physicians with large HIV practices to quickly check all of their patients' records to test hypotheses as they come up -- usually prohibitively difficult with the usual paper-based medical records. And it greatly reduces the work of identifying patients within a practice who are eligible for a prospective clinical trial. Medsys has been tested in daily use in the practice of Larry Bruni, M. D., for about two years. Dr. Bruni, the leader in the development of Medsys, has a large HIV practice, currently over 1300 patients, in Washington, D. C. (An interview with Dr. Bruni on treatment strategies appeared in AIDS TREATMENT NEWS #124, April 5, 1991.) This article will outline some of the highlights of the system, the computer environment in which it runs, and the business and practical arrangements to install it for community- based research, or for use in other clinics. The next step for interested medical professionals is to talk to persons who have used Medsys, or to see a demonstration, which provides a better feel for the system than a printed article can, and a better sense of its potential uses and importance. System Overview Medsys runs on a local area network of DOS (IBM-compatible) computers. As many terminals as needed can be connected; they can be in patient examining rooms if desired, in physicians' private offices, where blood is drawn for laboratory tests, and in the reception or accounting areas. (Passwords can prevent administrative employees from viewing patients' medical data.) In addition, physicians can access the system by telephone from home or while traveling, using portable computers, giving them complete access to patient records in an emergency, even during nights or weekends when no one is in the office. To use Medsys, physicians or staff at any available terminal can select a patient by typing a few letters of his or her name, or by using a patient identification number if available. The patient's name, address, demographics, and insurance information appears, and menus guide the user to appropriate parts of the electronic chart, including laboratory tests, radiology, pathology, problem list (of all current and resolved medical conditions diagnosed), medication list, and physical exam information. Data can be added or changed, and a patients' medical history can be displayed immediately, in various tabular or graphic forms, either on the screen or on paper. Many clinical laboratories now transmit results automatically by telephone to the offices of the physicians who ordered the tests. Usually the results are printed on paper as they come in, but with Medsys they go directly into the database as well; no retyping is required. (A person must intervene, however, before the data goes into the patients' charts. Since there can be incompatibilities or errors, such as slight differences in the spelling of a patients' name by the physicians' office vs. the laboratory, or notes to the physician from the laboratory, human examination is required to assure accuracy. It takes only a few minutes a day to post the labs in Dr. Bruni's 1300-patient practice.) Laboratory tests include chemistry panels, drug levels, endocrinology, hematology, immunology, microbiology, p24 antigen and antibody, serology, T-cell subsets, and urinalysis. Some of these categories (such as chemistry and microbiology) have submenus which are selected for display or editing of the data. Normal ranges for the same test (e.g. T-helper count) often differ between laboratories. Medsys records the normal values for each test used in the clinic or physicians' practice, and marks high or low patient laboratory results to call attention to them. New tests or new laboratories can be added, or existing values changed, by the physician's staff when necessary. Patients' records also include the pharmacy at which they usually fill prescriptions, and formatting information for specimen labels, which are printed as needed by Medsys. The problem list is kept by ICD-9 codes (International Classification of Diseases). The ICD-9 directory is included in Medsys, so users can search it for keywords and do not need to have the printed volume available to look up the codes. Usually data is entered by selection from lists (of diseases, medications, tests, findings, etc.), instead of by typing in text. This system saves time, avoids spelling errors or incompatible synonyms, and facilitates research by helping to make the computerized data compatible between different physicians' practices. When the physician decides on tests, specimen labels are automatically printed at the appropriate departments. The system also computes the bill for the visit, which is usually ready by the time the patient gets to the front desk. Not everything in the database is patient information. Other sections record consultants, pharmacies, hospitals (which works like "consultants," except that it also has menu choices for departments and staff, including the best persons and phone numbers to call during any shift), vendors, drugs and companies, services, and friends. Another section keeps the appointments and other schedule information for physicians and staff. Research and expanded-access protocols can also be entered into the system. For research use, data can be transmitted (by telephone if desired) without patient identifiers to other sites, to be combined for community-based research. Also, an interface between Medsys and SAS (a standard statistical analysis software package) is now being developed. Business Arrangements Medsys was created by the National Community Research Initiative (NCRI), a nonprofit organization. Medical Office Management Systems (MOMS), a for-profit corporation, sells Medsys commercially. MOMS owns Medsys, while NCRI has an unlimited license for HIV research. MOMS is also customizing Medsys for oncology and cardiology, which requires adding additional laboratory tests, and other minor modifications. MOMS sells Medsys for $25,000, which includes installation and training; there is also a $2500 per year maintenance fee. This does not include the cost of the computers; usually these are ordered in advance, before the MOMS staff travels to the site for installation. NCRI is providing Medsys free (except for the cost of computers and the maintenance fee) to HIV practices and clinics which support community-based research and agree to certain restrictions -- the main one being not to provide data collected through this software to third parties without the permission of NCRI. MOMS is working with Curaflex, headquartered in Ontario, California, to set up a national network of community-based research sites which use the Medsys software. The (anonymous) patient information from all these sites will be combined to quickly identify patients eligible for new clinical trials. Later, data from the trials will be sent to a biostatistical center for analysis. Such a system has considerable commercial potential, since the FDA is moving toward earlier approval of drugs for life-threatening conditions, while requiring that more research be done in postmarketing studies. Community-based trials, which are conducted through physicians' offices, are ideal for such studies, since the drugs are already in standard use and available by prescription. Software such as Medsys should enable pharmaceutical companies to get answers faster and less expensively, when the FDA asks for particular information. Technical For those interested in the system internals, Medsys is programmed in Foxpro, a commercially available database language, and uses the SQL query language. The software is table-driven and easy to modify, which allowed its rapid evolution in Dr. Bruni's practice; when he wanted a change, the programmer could quickly provide it. Recommended equipment for running Medsys is a 486 computer (it can run on a 386); a mouse is optional. Medmodem*, the part of Medsys which controls the modem (for receiving laboratory test results, allowing remote access to patients' records by the physician, and sharing research data) can use a 286. The computers are connected with a Novell local area network. Comment Before publishing AIDS TREATMENT NEWS, this writer developed computer software, and was particularly interested in making it easy to learn and use. In this respect Medsys has done very well. Medical staffs are already oriented to the system before training begins, because they are familiar with its elements -- the individual patients in the practice, clinical and laboratory findings, medications, prescriptions, pharmacies and other vendors, specialists and consultants, calendars and appointments, etc. At every point the screen shows what the user's options are, so it is seldom necessary to consult the manual. And with proper hardware the system is fast, usually responding immediately to user choices, even with 1300 patients in the database in the practice where we saw the software demonstrated. The benefit is not only in saving staff time, but also in allowing people to work at their own rhythms, instead of having to change to accommodate the computer. We believe this system can contribute significantly to the computerization of medical records, which would greatly facilitate both retrospective and prospective community-based research. For More Information For more information about the Medsys system, contact Peter H. Anestos, President, NCRI, Suite 201, 801 Pennsylvania Ave., S. E., Washington, DC 20003-2167, phone 800/466-0854. ***** AIDS TREATMENT NEWS Selected Index Compiled through 1992 by Denny Smith and Thom Fontaine This index lists selected topics from past issues of the newsletter which still seem relevant -- and obviously the more recent the issue, the more current will be the information. Note that the entries listed here will be found in the text of one or more articles in the issue(s) listed, but not necessarily in the table of contents. TOPIC ISSUE NUMBER(S) 3TC 140 5-fluorouracil/5-FU 122, 129 566C80 (atovaquone) 123, 129, 133, 139, 160, 164 acemannan 157 ACT UP 146, 147, 165 activism 147,151, 164 acupuncture 130, 157 acyclovir (Zovirax) 83, 108, 115, 132, 133, 143, 165 adrenal glands 140 aerosol pentamidine 114, 129 AGM-1470 (see TNP-470) albendazole 129 alpha APA 159 alpha interferon 87, 119, 122, 133, 154, 155 alternative treatments 153, 157, 158 amikacin 109 amphotericin B/liposomal AmB 117 Ampligen 119 anemia 82 angiomatosis 129 Antabuse (disulfiram) 132 anti-angiogenesis 117, 122, 135, 141 anti-idiotype antibody therapy 93, 110 antioxidant 152 antisense 141 antivirals 158, 164 aphthous ulcers 133 Asacol 109 aspirin 109, 118 atovaquone (566C80) 123, 129, 133, 139, 160, 164 azithromycin 113, 124, 132, 133, 136,139, 152 AZT(zidovudine,Retrovir) 143, 144, 145, 150, 154, 155, 158 bacillary angiomatosi 129 bacteremia 129 bacterial infections 120 Bactrim (co-trimoxazole, TMP-SMX) 114, 123, 129, 147, 152, 161 benefits 74, 76, 105, 144 beta carotene 134, 158 BHT 10, 71 BI-RG-587 117, 125, 127 biological response modifiers 120, 122 bitter melon 155, 157 bleomycin 122 blue-green algae (sulfolipids) 87, 99 breast cancer 145 buyers' clubs 143, 144, 145 cancer 122, 126, 135, 139, 162 candidiasis (thrush) 133 capsaicin (Axsain, Zostrix) 121 CD4 (recombinant soluble) 158 CD4-PE40 130 CD8 expansion 151 CDA (chlorodeoxyadenosine) 110 chemotherapy 122, 135 children/infants 120, 123, 124, 130 Chinese medicine 68, 126, 153, 158 chiropractic 130 cholera 152 Chronic Fatigue Syndrome (CFIDS) 132 cimetidine (Tagamet) 122 ciprofloxacin 152 clarithromycin 113, 124, 129, 137, 139 clindamycin 111, 129 clinical trials 116, 141, 142, 144, 149, 154 clofazimine (Lamprene) 141, 149 CMV 124, 129, 133, 138, 146, 149 coenzyme Q-10 (ubiquinone) 119, 124 cofactors 119, 124 colitis 133 combination therapies 115, 119, 145, 149, 150, 154, 155, 156 community research 105, 143 compound Q (trichosanthin) 119, 155 computer resources 114, 116, 124, 154, 165 cortisol 140, 150 CPFs 108 cryotherapy (liquid nitrogen) 122 cryptococcal meningitis 117, 129 cryptosporidiosis 95, 107, 111, 113, 124, 129, 133, 139 cytarabine(ARA-C) 129 d4T 158, 159, 161 dapsone 114, 125, 129 daunorubicin 117, 122 ddC 115, 132, 141, 144, 145, 149, 150, 154 ddC/AZT 115,132, 145, 150 ddI 125, 131, 137, 141, 149, 150, 160 dementia 97, 101, 156 desensitization 147, 161 dexamethasone (Decadron) 79, 88, 93 dextran sulfate 89 DHEA (EL 10) 140, 150 diagnosis accuracy 119 diarrhea 133,141 diclazuril (Clinicox) 107, 157 disability regulations 144 doctor/patient relations 100, 111 doxorubicin (Adriamycin) 122 doxycycline 119, 124, 129 dronabinol (Marinol) 131, 133, 141 DTC (Imuthiol) 114, 131, 132 eflornithine (DFMO) 94, 95 encephalitis 79, 97 endocrine problems 140, 150 enteritis 133 eosinophilic folliculitus 161 epidemiology 124 EPO (erythropoietin) 150 Epstein-Barr Virus (EBV) 93 erythromycin 129 esophagitis 133 etoposide (VP-16) 122, 149 exercise therapy 157 FAACTS 119 Fansidar 108, 114 fetal tissue research 164 FIAC 94 FIAU 129, 133 Flagyl (metronidazole) 129 FLT (fluorothymidine) 119, 145 flu shots 138 fluconazole (Diflucan) 129, 133 folic acid (folate) 134 foscarnet (Foscavir) 71, 83, 94, 108, 110, 129, 133, 136, 138 fumagillin 122, 135 funding/lobbying 97, 99, 145, 146, 151, 156, 157 G-CSF 122 gall bladder 124, 133 gamma globulin 119, 120, 124, 129, 152, 155 ganciclovir (DHPG, Cytovene) 108, 124, 129, 133, 138 gastritis 133 gene therapy 158 gentamicin 109 germanium 90 glutathione 88, 92, 93, 119, 121, 138, 141, 152, 157 glycyrrhizin 17, 103, 115 GM-CSF 122 gp120 (vaccine) 130, 149 gp160 (vaccine) 130 health care politics 120, 125, 126, 132, 135, 136, 137 hemophilia 102, 103, 132, 137 heparin, substitutes 122, 146 herpes/shingles 83, 115, 133, 138, 146, 149 HGP-30 (vaccine) 130 histoplasmosis 96 HIVIG (hyperimmune globulin) 148, 153, 154 HPMPC 149 human papilloma virus (HPV) 146 Humatin (paromomycin) 107, 111, 129 hydrogen peroxide 132, 134, 152 hypericin 91, 96, 117, 125, 138, 141, 146, 155 hyperimmune milk (colostrum) 49, 95, 107 hyperthermia 104, 122 ibuprofen (Advil) 109 idarubicin 122 IGF-1 146, 150 immigration politics 114, 120, 125, 128, 129, 134 immune globulin (IVIG) 119, 120, 124, 148, 152 immune restoration 151 immunomodulators 119, 151, 158 immunotoxins 140 Imuthiol (DTC) 114, 131, 132 indomethacin 109 insurance 120, 136 interferons 87, 101, 108, 114, 119, 122, 132, 151 interleukins (IL-2, etc.) 119, 122, 151 international conference, Amsterdam 153, 154, 155, 156, 157, 158, 159 international edition, ATN 155, 159 international travel 128, 152 Iscador (mistletoe compound) 92 isoprinosine 106 ITP 48 itraconazole (Sporanox) 96, 161 IVIG 119, 120, 124, 148, 152 Kaposi's sarcoma (KS) 117, 122, 129, 135, 162 Kemron 97, 101, 114 ketotifen 158 L661 & L229 139 L671,329, L687,781 114 L697,639, L697,661 118, 125 labor unions 123 lacquered mushroom 157 laser treatments 75, 96 lentinan 19, 73 letrazuril 133 leucovorin 49, 52, 79, 108 levamisole 122, 124 lignins 158 liposomes 109, 117, 122 liquid nitrogen (cryotherapy) 122 lithium 119 liver problems 103, 133 Lyme disease 132 lymph tissue 153 lymphoma 93, 110, 136, 140 MAI/MAC 132, 136, 137, 139, 141, 149, 152, 158 marijuana 131, 133, 139, 141, 148, 156 Marinol 131, 133, 141, 148 mebeciclol 95 medical research funding 163 Megace (megestrol acetate) 133, 150 MEK 99 melanin 107, 139, 141, 144 Mepron (atovaquone) 123, 129, 133, 139, 160, 164 mexiletine 121 microsporidiosis 129, 133, 139 mitoxantrone 93, 122 molluscum contagiosum 133 monoclonal antibodies 129 mycoplasma 95, 108, 124, 129 myopathy 119 N-butyl-DNJ 149 N-of-one trials 153 NAC 88, 92, 93, 119, 121, 138, 141, 152, 157 naltrexone 16, 52, 119 National Commission 154 nausea 131, 139, 141 neopterin 86, 100 neupogen (G-CSF) 122 neurology 156 neuropathy 121, 130, 156 neuropsychiatric concerns 97, 101, 126 neutropenia 94 NIH, report on 156 nonsteroidal anti-inflammatories 109 nutrition/malnutrition 133, 134, 141, 152, 158, 163 octreotide (Sandostatin) 95, 127, 141 on-line computer systems 154 Oncolysin B 136 oral interferon 97, 101, 114 ozone 80 p24 (vaccine) 130 p24 antibody 100, 119 p24 antigen 100, 119 pain medication 154 parasites 133 passive hyperimmune therapy (PHT) 67, 92, 148, 149, 151, 158, 165 passive immunotherapy 67, 92, 148, 149, 151, 158, 165 pathogenesis 147, 156 patient/doctor relations 100, 111 PCR 62, 144 peliosis hepatis 129 pentamidine 114, 129 pentosan polysulfate 117, 122 pentoxifylline (Trental) 133, 145, 156 people of color 86, 99, 121 peptide T 84, 119, 126 Persantine (dipyridamole) 79 pets (infection hazards) 79 PF4 (recombinant) 122 pharmacies 64, 86 physician interviews 106, 119, 124, 126, 132, 135, 142, 143, 149, 160 piritrexim 122 PMEA 156 PML 115, 129, 153, 156 pneumocystis 114, 115, 123, 129, 139, 147 pneumonias, bacterial 119 policy 127, 136, 140, 146, 155, 156, 157, 158, 164, 165 polio vaccine 147 political funerals 157, 158, 160 polyadenylic polyuridylic acid 158 poppers 160 prednisone 150 pregnancy 90, 112, 153, 154 primaquine 113 prisons 106, 125, 126, 130, 149, 151, 161 probenecid 86 procysteine 152 programmed cell death (apotosis) 156 prophylaxis/prevention 114, 119, 123, 129, 158, 161 propolis 37 Prosorba column (protein A) 75, 122 protease inhibitors 117, 156 psychological health 161 PWA coalitions 117 pyrimethamine (Daraprim) 104, 108, 114, 129 R 82913 131 radiation therapy 73, 93, 110 recreational drugs 119 resource list 143, 144 reverse transcriptase inhibitors 117 ribavirin 141 ricin-A 140 rifabutin (Ansamycin) 149, 158, 160 rifampin 102 Ro 24-7429 141, 142, 153 roxithromycin 95 Salk vaccine (HIV) 98, 130 San Diego CRG 143 Sandostatin (octreotide) 95, 127, 141 scabies 98 SCH 39304 99 Septra (co-trimoxazole, TMP-SMX) 114, 123, 129, 147, 152, 161 shiitake 19 SP-PG 135, 141 sparfloxacin 129, 132, 152 spiramycin 79, 95, 107 stem cell research 151 steroids 114, 115, 133, 150 sulfadiazine 104, 108, 129 sulfolipids (blue-green algae) 87, 99 sunlight 58, 124, 161 superantigens 151 surrogate markers 119, 144 symptoms 100, 119, 124 syphilis 124 T4-helper (CD4) cells 119, 144, 147 tat inhibitors 127, 128, 132, 141, 142, 153 tests (blood values) 119, 144, 151 thalidomide 133 THF (thymic humoral factor) 151 thymopentin (TP-5) 123, 149 (and Jan. 1993) TI-23 108, 129 TIBO derivatives 97, 131 TLC-G-65 109 TNP-470 (formerly AGM-1470)) 135, 141, 162 toltrazuril (Baycox) 111 toxoplasmosis 109, 113, 123, 124, 129, 139, 152 TP-5 123, 149 (and Jan. 1993) TPN feedings 133 transfer factor 47, 119 travel 152 treatment access 115, 116, 118, 119 treatment information sources 121, 162 treatment strategy 100, 111, 119, 124 trental 133, 145, 156, 158 tretinoin (Retin-A) 122 trifluridine (Viroptic) 115 trimetrexate/leucovorin 49, 52,79, 108 tuberculosis 106, 161 tumor necrosis factor (TNF) 88, 145, 156 ultraviolet light 161 vaccines 130, 149, 151, 152, 164 valley fever (coccidioidomycosis) 41, 96 Velban (vinblastine) 73, 122 vidarabine (Vira-A) 79, 94 vinblastine, vincristine 73, 122 viral quantitation 144 vitamin A 134, 152, 158 vitamin B 134, 152, 158 vitamin B-12 158 vitamin C 111, 152, 157, 158 vitamin D3 analogs 122 warts 112, 118, 146 women 90, 112, 115, 118, 130, 153, 154 yohimbine 159 zinc 134, 158 Zovirax (acyclovir) 83, 108, 115, 132, 133, 143, 165 ***** AIDS TREATMENT NEWS Published twice monthly Subscription and Editorial Office: P. O. Box 411256 San Francisco, CA 94141 800/TREAT-1-2 toll-free U. S. and Canada 415/255-0588 regular office number 415/255-4659 fax Editor and Publisher: John S. James Medical Reporters: Jason Heyman John S. James Nancy Solomon Reader Services and Business: David Keith Thom Fontaine Tadd Tobias Rae Trewartha Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. We interview physicians, scientists, other health professionals, and persons with AIDS or HIV; we also collect information from meetings and conferences, medical journals, and computer databases. Long-term survivors have usually tried many different treatments, and found combinations which work for them. AIDS Treatment News does not recommend particular therapies, but seeks to increase the options available. Subscription Information: Call 800/TREAT-1-2 Businesses, Institutions, Professionals: $230/year. Nonprofit organizations: $115/year. Individuals: $100/year, or $60 for six months. Special discount for persons with financial difficulties: $45/year, or $24 for six months. If you cannot afford a subscription, please write or call. Outside North, Central, or South America, add air mail postage: $20/year, $10 for six months. Back issues available. Fax subscriptions, bulk rates, and multiple subscriptions are available; contact our office for details. Please send U. S. funds: personal check or bank draft, international postal money order, or travelers checks. VISA, Mastercard, and purchase orders also accepted. ISSN # 1052-4207 Copyright 1992 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used. &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&