Date: Sat, 03 Dec 1994 01:00:42 -0800 (PST) From: "John S. James" X-Lines: 925 AIDS TREATMENT NEWS Issue #212, December 12, 1994 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS 3TC Plus AZT: Important Treatment Advance? Vpr -- A Viral Protein Is Found to Activate HIV Untold History: Treatment Activism and Growth Hormone New Computer Communication for AIDS Agencies -- HandsNet AIDS/HIV Forum Threats to Ryan White, AIDS Funding? Call for Information ***** 3TC Plus AZT: Important Treatment Advance? by John S. James There has been much excitement among researchers and activists about the results of European trials, in over 300 patients, which compared the experimental antiviral 3TC (also called lamivudine), used in combination with AZT, to AZT alone. The results, as measured by blood tests at intervals for up to 48 weeks, were considerably better than researchers would have expected with approved antiviral drugs or combinations. Some questions remain, however, because these trials were not designed to detect differences in disease progression; and there have been well-publicized cases when smaller improvements in blood tests led to little or no improvement in disease progression or ultimate survival. But trials to confirm this ultimate benefit will begin early in 1995 and then will probably last well over a year; those who do not want to wait for definitive proof will need to make the best decisions possible from the information which is available. (Some confirmatory information -- but also based on blood-test improvements, not clinical disease progression -- will probably be presented at the Second National Conference on Human Retroviruses and Related Infections, January 29 - February 2, 1995, in Washington, D.C.) We were not at the Second International Congress on Drug Therapy in HIV Infection, in Glasgow, Scotland, where the 3TC results were released on November 20. This article is based on conversations with several people who were there, and on press releases which summarized the data presented. 3TC Background 3TC is a nucleoside analog antiviral -- in the same general class as AZT or ddI -- which has been in human trials as an experimental HIV treatment for several years; in addition, it is also showing promise as a treatment for hepatitis B. Since October 1993 (earlier in Canada), 3TC has been available through an expanded-access program, for persons with T-helper counts under 300 who cannot tolerate, or do not benefit from, approved anti-HIV treatment (AZT, ddI, ddC, or d4T). This program is still open for enrolling new patients; for more information, see below. 3TC is being developed by Glaxo, which licensed rights to the drug in 1990 from BioChem Pharma Inc., a biotechnology company located in Laval, Quebec. Glaxo had discussed development arrangements with Burroughs- Wellcome, but decided to develop the drug itself when the new results were announced. In laboratory tests, 3TC has been found to be synergistic with AZT, meaning that the two drugs in combination work better than would be expected by adding their separate effects. One theory holds that this is because 3TC reverses HIV's resistance to AZT -- that when the virus has the mutation which makes it resistant to 3TC, it will be susceptible to AZT even if it also has the mutations which normally would confer AZT resistance. But other researchers believe that this proposed mechanism -- reversal of AZT resistance by 3TC -- could not explain the new data, which suggests that the synergy of the two drugs starts immediately, and then is maintained over time. AZT alone does not produce the same immediate improvement, even in AZT-naive patients in whom resistance would not be an issue. (Burroughs-Wellcome, which makes AZT, favors the former theory, while Glaxo, which makes 3TC, favors the latter.) More studies of drug resistance and synergy are now being conducted, and some new information should be available at the Human Retroviruses conference early next year. 3TC results for chronic hepatitis B (in HIV-negative patients) were released recently at a Chicago meeting of the American Association for the Study of Liver Diseases. Hepatitis B viral DNA become undetectable in all 22 patients treated with either 100 mg per day or 300 mg per day of 3TC. But treatment was stopped after 12 weeks in this study, and then the virus returned in 16 of the 22 patients, and remained undetectable in the other six -- five of whom had already failed interferon treatment. (For HIV treatment, at least 300 mg per day of 3TC is likely to be used indefinitely, suggesting that this HIV treatment may also control hepatitis B for those with both infections.) Historically, an earlier version of 3TC was called BCH-189. BCH-189 is a mixture of equal parts of 3TC and a molecule which is a mirror image of 3TC. The molecule not used in 3TC does have anti-HIV activity, apparently less than that of 3TC, but with a different drug-resistance profile. The Glasgow Results The results just presented at Glasgow came from two multi- center trials in Europe. A French study, involving 129 patients, was presented by Professor Christine Katlama from Paris; it compared 3TC plus AZT to AZT alone, in patients who had never taken AZT, or had taken it for less than four weeks. At entry, volunteers had a T-helper counts from 100 to 400 (median 256). They were randomly assigned to take one of the two drug regimens for 24 weeks, then they were allowed to take the combination for an additional 24 weeks (all 55 patients given the choice of switching to combination therapy chose to do so). The 3TC dose was 300 mg twice daily; the AZT dose was 200 mg three times daily. Those assigned to start the combination therapy had an average T-helper increase of 80 at week 24, and an average of 49 over their starting value at week 48. The level of plasma HIV RNA was reduced 86 percent at week 24, and 91 percent at week 48. The level of virus in blood cells (determined by a viral culture test, to show how infectious the blood cells were) was reduced 99 percent at week 24, and 99 percent at week 48. The comparison group, randomly assigned to take AZT alone for the first 24 weeks but then switched to the combination, had an average T-helper count decrease of 7 by week 24. By week 48, after 24 weeks on the combination, they had an average T- helper count increase of 40 above baseline. Plasma HIV RNA was reduced by only 36 percent at week 24, but by week 48 the decrease from baseline was 92 percent. The infectivity of the blood cells was reduced only 11 percent at week 24 (by AZT alone), but reduced 98 percent at week 48 (after 24 weeks on the combination). How do these results compare with those that might be expected from other combination treatments, such as AZT plus ddI? For T-helper count and plasma HIV RNA, the 24-week improvements are within the range one might expect from other successful combinations. What is important is that they were sustained at 48 weeks, with the patients appearing to be considerably better at that time than when they started. The best results, of course, were in the reduced infectivity of blood cells; but here we do not have similar values from other combination trials for comparison. A German study, testing the combination in AZT-experienced patients, was presented by Dr. Schlomo Staszewski from Frankfurt. This study compared AZT alone, AZT plus high-dose 3TC (300 mg twice daily, the same dose used in the French study), and AZT plus low-dose 3TC (150 mg twice daily). Like the French study, it required participants to have T-helper count between 100 and 400 at entry (the median entry value was 249 for the AZT-only arm, 232 for the combination of AZT plus high-dose 3TC, and 246 for the combination of AZT plus low-dose 3TC). These patients also had to have at least 24 weeks of prior treatment with AZT, but usually they had much more than that (mean prior AZT use, 24.9 MONTHS for the AZT- only arm, 22.1 months for the high-dose combination arm, and 24.4 months for the low-dose combination arm). A total of 223 patients were randomly assigned to one of these three treatment arms, and treated for 24 weeks. The 48- week data is not yet available; also, no virology data is available at this time. At 24 weeks, the T-helper count was 33 above the starting value in the high-dose combination and 36 above starting value with the low-dose combination. In contrast, those on AZT alone had an average T-helper decrease of 21 at week 24. All of the differences reported above for the French and German studies were statistically significant. And the drop- out rate in both studies was low, 12 percent at week 24 in the French study. The low drop-out rate, plus the fact that no one chose not to go onto the open-label combination treatment at 24 weeks, makes it unlikely that selection bias had much effect on the result. (A high drop-out rate can falsely make a drug look good, since those who find out that they are doing poorly are more likely to leave the study, while those doing well are more likely to stay.) Note: 48- week data was available on only 72 patients of the 129 in the French study. This difference is not due to drop-out, but to the fact that only some of the patients had reached the 48- week point at the time the data was analyzed for presentation at the Glasgow meeting. These studies were not designed to detect differences in clinical disease progression. In the French study, only one patient in the combination arm had a major opportunistic infection (esophageal candidiasis, which started five days into the study). In the German study there were 42 "progression endpoints," with no statistically significant differences between the arms, but a trend favoring the combination treatment for major opportunistic conditions at least, according to data presented in Glasgow. We have not seen a breakdown on the minor events. There were no unexpected toxicities of the combination treatment, and no statistically significant differences in side effects between the combination treatment and AZT alone. Future Results and Studies, and Prospects for Approval Two additional clinical trials in the U.S. and Canada are now finishing; results should be available early next year. These studies, in patients similar to those in the European trials presented at Glasgow, are comparing the 3TC plus AZT combination not only with AZT alone, but also with 3TC alone, and with AZT plus ddC. In addition, Glaxo's expanded-access program, for patients with T-helper counts under 300 who cannot successfully use approved treatments, has now enrolled over 6,000 persons. In North America they have been randomly assigned to receive 150 mg or 300 mg twice daily. This program is not expected to provide much information about the effectiveness of the drug, but the long-term experience with a large number of people should help provide assurance that there are no major unexpected toxicities. In early 1995, Glaxo expects to start large-scale studies to make sure that the positive blood-test results of the 3TC plus AZT combination do translate into slower disease progression and/or longer survival of patients. Glaxo has also taken the lead in testing 3TC in children in parallel with tests in adults, so that the drug can be approved for pediatric use without the delays which have been a major problem with other HIV drugs. Results of an early clinical trial of 3TC in children were presented as early as June 1993, at the International Conference on AIDS in Berlin. Assuming that the North American studies which are now finishing confirm the European results, Glaxo is likely to apply for approval for 3TC in early 1995, under the FDA's accelerated-approval regulations. Accelerated approval is intended for just this kind of situation: where a drug has shown good results in blood tests improvements, and long-term "clinical endpoint" trials, designed to confirm delay in disease progression, are underway. The Expanded Access Program The expanded-access program for 3TC is still open for enrollment. This program is for patients who have a T-helper count under 300, and cannot successfully use approved antiretrovirals (either because of toxicity, or because those drugs are not working for them). We do not know the details of what evidence is required that approved drugs have failed. Physicians experienced with the program would have the best information on this. In the current program, combining the 3TC with AZT or other antiretrovirals is "strongly discouraged" -- but apparently not cause for expulsion from the program. Glaxo is now considering changing the program to allow patients who have progressed on AZT, but are tolerant of it, to use the drugs in combination. We do not know whether or not 3TC could be used in combination with ddI, ddC, or d4T, but cross resistance with ddI and ddC has been reported. Individuals in North America who would like information on the open label program should have their physicians call 800/248-9757. [Note: AIDS writer Mark Mascolini, who attended the Glasgow conference, assisted with the research for this article.] ***** Vpr -- A Viral Protein is Found to Activate HIV by John S. James Vpr, a protein produced by HIV and found in the bloodstream of persons with HIV disease, has been found to activate HIV at low concentrations -- lower than those often found in patients' blood. A recent paper, by four University of Pennsylvania researchers, presented considerable evidence that Vpr may be involved in the development of HIV disease, stimulating latently infected cells to become productively infected when the body loses the ability to produce enough of the right antibodies to keep Vpr activity in check. Vpr also affects many kinds of human cells, so it could contribute to the damage cause by HIV, in addition to stimulating the virus itself. This is important because Vpr might easily be a target for antiviral therapy, for example by administering anti-Vpr antibodies. The evidence that Vpr may contribute to HIV disease appears in "Serum Vpr Regulates Productive Infection and Latency of Human Immunodeficiency Virus Type 1," by David N. Levy, Yoseph Rafaeli, Rob Roy MacGregor, and David B. Weiner, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, U.S.A., November 1994. The researchers tested the blood of eight persons with AIDS, and eight others with asymptomatic HIV infection, and found that Vpr was present in each. The levels found were correlated with the levels of p24, another protein produced by HIV. And in three patients, who had frozen blood serum collected before and after the development of late-stage disease, the Vpr increased greatly (about ten fold), comparable to the increase in p24. HIV negative blood was tested as a control, and no Vpr was found. Vpr was also found in the cerebrospinal fluid of five HIV- positive patients with neurological disease; the levels were about the same as in the blood. In laboratory cultures, Vpr greatly activated expression of HIV. The amount of the effect was dose dependent, with some activity found at concentrations as low as 50 times less than concentrations found in the blood. [The blood concentrations included Vpr which was bound to antibodies, and therefore would not stimulate HIV. These antibodies may be helping the body establish control of the virus after the initial primary infection, and keep control during the period of clinical latency of the illness. As immune-system damage accumulates, however, the ability to continue controlling Vpr may be lost.] Blood serum from rabbits immunized with Vpr greatly inhibited the activation of HIV by Vpr, in laboratory tests. Similarly prepared serum from non-immunized rabbits had no effect. As an additional control, in another experiment, another substance (PMA) -- not Vpr -- was used to activate HIV; in this case, the serum from the immunized rabbits had no effect. These experiments together show that the viral activation did result from the Vpr. Another test showed that Vpr produced somewhat more and longer-lasting viral activation than either PMA or PHA, two substances often used in laboratory tests to activate HIV. The authors mentioned the possibility that Vpr might particularly increase HIV activity in localized areas, such as the germinal centers of lymph nodes, where many infected cells are close to each other and, as a result, the level of Vpr may be high. A November 8 article in the PHILADELPHIA INQUIRER, based on an interview with Assistant Professor David Weiner, who headed the study, suggested that Vpr and antibodies to it might be part of a "regulatory loop" that is a major determinant of HIV disease progression. Dr. Weiner suggested that either antibodies or drugs could be used to block the action of Vpr. Comment The obvious way to find out whether this research lead has immediate practical value would be to prepare anti-Vpr antibodies and inject them into persons with HIV, to see if the viral load is decreased. Viral load -- plasma HIV RNA -- can now be measured with a simple, commercially-available blood test (either quantitative PCR, or branched DNA). Anti- Vpr drugs might take a longer time to discover and develop. A trial could use monoclonal antibodies, which are made by genetically-engineered cells. This approach has the disadvantage that it would first be necessary to find out exactly what antibodies are needed, and then engineer them. And the lack of money for producing new monoclonal antibodies has been a serious barrier to AIDS research in other projects. It might also be possible to obtain the antibodies from the serum of immunized animals -- a familiar, low-tech approach which has long been used in medicine. ***** Untold History: Activism and Growth Hormone by John S. James A glimpse of a largely untold history was published November 25 in the BAY AREA REPORTER, a gay newspaper in San Francisco. The article, "Activists Zap FDA Over Growth Hormones," by Jeff Getty of ACT UP/Golden Gate, looks at one treatment (recombinant human growth hormone for wasting syndrome) but illustrates a larger story -- the real determinants of whether or not critically important medicines ever get studied, and whether they get to doctors and patients who want them even when the studies have found that they work. The case of growth hormone shows how much effective medical care depends on quiet, behind-the-scenes work of activists from such organizations as ACT UP/Golden Gate, Healing Alternatives Foundation, and Project Inform in San Francisco, and others elsewhere. Before activists got involved, the major trial of human growth hormone was failing because it could not recruit patients. Activists diagnosed the problem -- the trial's exclusion criteria, which kept out the very people who needed the treatment in the first place. They got the criteria relaxed, and the trial filled quickly. Now the study has been successful, but red tape is keeping the drug from patients. A major problem today seems to originate in international political struggles around the European Economic Community, with patients being used as pawns. The plant to manufacture the drug is in Switzerland, and it is currently under construction to increase capacity. Apparently the FDA no longer accepts Swiss inspection, due to international politics, but must inspect the plant itself -- and it does not inspect plants under construction, leaving U.S. access to this particular source of drug on hold. (There are other potential sources, but they have problems of their own.) As we go to press, activists have forced meetings to try to get the plant-inspection problem resolved. These kinds of problems happen all the time. What is most astonishing is that there is no established system in place to deal with them. Still, after almost ten years of the epidemic, no one is responsible. The impact of this responsibility gap not only on AIDS, but on medical research for cancer, Alzheimer's, and other serious or life- threatening diseases, must be unimaginable. The opportunities to improve medical research for the benefit of everyone, just by applying the most basic principles of effective management which have long been developed for industry, must be immense. The November 25 article is the first in a series by ACT UP/Golden Gate in the BAR AREA REPORTER. We hope to see more on the hidden history of activism in drug development, so that the public will understand the importance of this work. Note: For a copy of "Activists Zap FDA Over Growth Hormones," send a self-addressed stamped envelope to: Bay Area Reporter, 395 Ninth St., San Francisco, CA 94103. ***** Computer Communication for AIDS Agencies -- HandsNet AIDS/HIV Forum by Tadd Tobias and John S. James A new computer communication system, designed for government and nonprofit AIDS agencies, was announced October 31 at the National Skills Building Conference in Atlanta. This project uses HandsNet, already a major tool for electronic communication among nonprofit organizations, for a new project to improve communication and coordination among agencies working in AIDS. About two dozen agencies and organizations have joined so far, including (partial list in alphabetical order): AIDS Action Council, AIDS Project Los Angeles (Sacramento office), AIDS Treatment News, Beth Israel Hospital (Boston), Center for AIDS Prevention Studies, Centers for Disease Control National AIDS Clearinghouse, Funders Concerned about AIDS, Gay Men's Health Crisis, Kaiser Family Foundation, National Minority AIDS Council, Office of the National AIDS Policy Coordinator, Project Inform, Robert Wood Johnson Foundation, San Francisco Black Coalition on AIDS, San Francisco General Hospital AIDS Program, and Upper Midwest AIDS Coalition. Also, 51 Ryan White Special Projects of National Significance (SPNS) have now been funded to come online, and in addition the National Community AIDS Partnership will fund several sites. Hopefully, "The AIDS/HIV Forum will eventually link thousands of AIDS service organizations throughout the United States with the latest prevention, policy, treatment, funding and resource information. HandsNet will provide support and training to facilitate the flow of information between participating organizations." (Quote from October 31 press release from the Henry J. Kaiser Family Foundation.) The Kaiser Family Foundation funded this project with a $300,000 two-year grant, and Apple Computer provided $50,000 in equipment. This article will outline how the system is used, note its principal strong points and limitations, and examine the controversy over whether this project has unnecessarily duplicated other work. Background: What is the HandsNet AIDS/HIV Forum? HandsNet is a nonprofit organization which provides a computer communication system designed for human-service agencies, in areas such as housing, education, rural issues, legal services, substance abuse, and other health services. HandsNet has over 3,500 users; and many forums already exist for agencies in various fields, but so far this system has had little use in AIDS. The AIDS/HIV Forum is a new project to improve communication and information flow among AIDS agencies, by providing them with training and technical support to facilitate their use of HandsNet, and to coordinate the development of information resources on that network. What is now being done for AIDS is similar to what has previously been done for other human-service areas. HandsNet provides electronic mail between its users, who can also send and receive mail to non-HandsNet users on the Internet; it allows users to create their own mailing lists, to automatically distribute email to anyone reachable through the Internet. Also, the various forums (such as the AIDS/HIV Forum) contain public areas in which users can post information. This allows agencies to post action alerts, discuss policy issues, explain their projects, network with people in the same or other fields, etc. And it also means that most of the information in these public areas is contributed by others working on the front lines of the field, increasing its currency and relevance. Many other systems provide similar email facilities. HandsNet is especially easy to learn to use, because it does an unusually good job of shielding users from computer details which they do not want or need to know about. HandsNet also provides an effective and flexible way of posting information coherently in public areas; and it includes a keyword search to find any reference to a topic of interest, no matter where it was posted. An important advantage of HandsNet is that it is already heavily used by nonprofit human-service agencies. HandsNet encourages communication across the different interest areas -- for example, between AIDS and other health issues, children and family, housing and community development, hunger and nutrition -- by sending a Weekly Digest (a selection of policy, program, and resource articles posted that week) to all HandsNet members. By scanning this weekly summary -- usually about four single-spaced printed pages in length -- one can learn what is happening now in human- services areas other than one's own, and easily communicate with those involved. (Now that AIDS has a presence on HandsNet, activists in other areas are being exposed to AIDS news and issues they might not otherwise have seen.) John Laird, a former mayor of Santa Cruz, California, who has also served as executive director of the Santa Cruz AIDS Project, has been hired by HandsNet to coordinate the development of the AIDS/HIV Forum. Individuals can get accounts on HandsNet -- you do not have to be an organization. However, HandsNet is designed for nonprofit agencies; individuals seeking AIDS information by computer will generally find other systems more suited to their needs, and less expensive. What's On the HandsNet AIDS/HIV Forum? On November 23 we spent about an hour exploring part of the AIDS/HIV Forum. Here are some of the items which caught our attention. Since they included email addresses, the people involved can be reached by electronic mail from HandsNet or from other systems connected to the Internet. * Background on the AIDS/HIV forum itself, including a list of the 39 people at more than two dozen organizations currently online, and explanations of how to post different kinds of messages in different public areas. * A Treatment Forum containing the last two years' issues of AIDS TREATMENT NEWS, treatment fact sheets and other information from Project Inform, and other treatment information which is now being prepared and added. "The Treatment Forum will be managed by the National AIDS Treatment Information Project, funded by a Kaiser Family Foundation grant and consisting of staff members from Boston's Beth Israel Hospital, the Gay Men's Health Crisis in New York, and the AIDS Program at San Francisco General Hospital...(It) will be part of a larger national project, which will include the development and distribution of treatment information through a fax-back system as well as these electronic means." * Background on TAN (the Treatment Action Network), Project Inform's "national network of activists who contact elected officials, government administrators and drug companies on critical HIV treatment and research issues." (For more information, call Tom Wonsiewicz, TAN coordinator, at Project Inform, 415/558-8669 ext. 205.) * A Policy Forum, maintained by the AIDS Action Council. It includes advocacy and coalition-building tips for AIDS service organizations and for community-based organizations. It has sections for Budget, Housing, Care, Research & Treatment, Prevention, Women's issues, Ryan White, Civil Rights and Immigration, Federal Agencies, and State Policies. There is a weekly AIDS Action Update, and an Election Update. * The Republicans' Contract with America. The HandsNet Weekly Digest for November 25 was replaced by a summary of information about the Contract with America which is available on HandsNet. An overview, and four analyses of various aspects, are listed -- as is a December 13 telephone conference on welfare reform. There is a growing concern that "low-income households would be the clear losers, as they would gain little from the Contract's tax proposals and bear most of the burden from the resulting budget cuts." [We also note that people with AIDS, cancer, and other serious diseases are especially affected. Private insurance increasingly finds ways to dump those with serious illnesses onto Medicaid and other public health care, which will be targeted to finance simultaneously huge tax cuts, deficit reduction, and major prison and military spending. Already many people with AIDS -- probably thousands -- have been forced to live on the streets; the new proposals are likely to make things worse.] * The November 19 HandsNet Weekly Digest. It notified readers of a new report on AIDS in New York City -- now the leading cause of death of city residents between the ages of 25 and 44 -- with analysis concerning children, orphans, recent immigrants, and the homeless. Non-AIDS issues include: summer youth employment; new child and family resource centers now being established; where to go with health-care reform, including state programs; the new Congress and housing programs; agriculture worker pesticide protection; domestic violence; expanding free electronic access to government information; substance abuse treatment; and a California guide on how to get food, health, and other services for low- income people. * The AIDS Daily Summary, written by the U.S. Centers for Disease Control and summarizing AIDS news stories each business day. (This useful service is available on many computer-communication systems.) Here we found references to international press coverage on the new information about the combination of AZT plus 3TC, which will lead us to the original articles. And we learned of a November 21 WALL STREET JOURNAL report that Russia's consideration of a law to test all foreigners entering the country for HIV has caused "a flood of cancellations of trips," with an estimated decrease in tourist and business trips of up to 40 percent if the bill becomes law. We believe that the HandsNet AIDS/HIV Forum addresses an urgent need for better coordination among AIDS agencies. But in order to be successful, it will need to achieve a critical momentum of use, since new people will join only if those they need to communicate with are already there. Fortunately electronic mail itself is now achieving this momentum in AIDS work, with many, perhaps most, AIDS professionals and activists now having an email address on some system. This makes it easier for HandsNet, since the big initial hurdles of equipment, setup, and training have already been crossed. HandsNet can be used with either Macintosh, Windows, or MS- DOS compatible computers. Limitations, Disadvantages * Cost. HandsNet is more expensive than other systems; the minimum fee is $35 per month for one user's account, and most organizations actually spend about $35 to $40. (Organizations with more than one user can get substantial discounts.) Users get two bills: One is from HandsNet, and the other is from CONNECT, the company which provides the computer and software with which HandsNet runs. Cost goes up if one spends more than two hours per month online, or downloads more than about 20 single-spaced pages of information per month. The system is designed to allow users to minimize online time, so the average user's cost is not much more than the minimum. * Limited Internet access, at least for now. HandsNet users can send and receive email through the Internet; this means they can also subscribe to electronic mailing lists. But they cannot use Internet services such as World Wide Web or Gopher -- let alone set up their own information on these services for other people around the world to use. These Internet services are rapidly becoming more important, and they are available from other vendors for much less than the $35 per month minimum for using the HandsNet system. But it means opening another account, and setting up and learning different software. HandsNet plans to offer World Wide Web and Gopher access by mid 1995. But at current prices for online time and downloading of information, using the Internet through a HandsNet account would be considerably more expensive than alternatives. If Internet use turns out to be too expensive or otherwise not feasible, then the AIDS community could move onto HandsNet and still end up behind the computer- communication learning curve in two or three years. * Proprietary software. HandsNet can only be used with CONNECT's proprietary software -- not with the standard terminal programs which most systems use. This can be inconvenient -- for example, when checking one's email while traveling. Controversy: Duplication of Effort? There has been controversy about the decision by the Kaiser Family Foundation to start a new AIDS communication system, instead of building on the work which had been done before. Many of those familiar with computer communication in AIDS think that the new system should have been built around AEGIS (AIDS Education General Information System) a low-budget international network which is widely considered the best single source of AIDS information for individuals. Sister Mary Elizabeth, who started the AEGIS system, expressed the concerns of many of the AIDS activists who have been using computer communication for years: "HandsNet has received substantial funding to develop services which are otherwise available free of charge. HandsNet and CONNECT will benefit by having more paying customers, but what happens when the two-year Kaiser grant ends? Will the AIDS/HIV Forum continue to offer organized and moderated information and conferencing resources? Or will it be left to volunteer effort to maintain the Forum? "The end result, the quality and accessibility of information, will be largely dependent on the ability of AIDS/HIV Forum organizers to secure ongoing funding to maintain and expand outreach and training, as well as information management. You can bet that HandsNet and CONNECT won't foot the bill. I'm certain John Laird will do a good job, to the best of his ability, but it is a gamble that his position will continue. I don't understand why funds weren't dedicated to further develop existing AIDS information systems which grew out of the grassroots response. These systems have an excellent track record and user base, and operate for much less expense than do commercial and government ventures. "For less than $20,000 per year, AEGIS makes high-quality AIDS information available through state-of-the-art computer technologies. A $300,000 grant would have gone a long way, for years to come, to further expand our world-wide network and build on our active user base of over 1,500 persons. It would only take $25,000 to develop full Internet access for AEGIS, and $15,000 a year to support it thereafter. Instead of spending $300,000+ over two years for an inferior service, doesn't it make sense to spend that money more wisely by cooperating with existing AIDS information providers to support their ongoing efforts for the coming decade? "How will community access be assured? People who need the information the most don't have the money to subscribe to a commercial system, especially when the free services currently available offer much more comprehensive information in a user-friendly, supportive environment." Comment Computer communication is moving and changing so rapidly that no one can predict what will be most successful. If it had been our choice, we might have chosen the Internet and AEGIS as the basis for an AIDS communication system, instead of HandsNet. But there are also strong arguments for choosing HandsNet. It has a proven track record in supporting agencies and working groups; AEGIS evolved more for providing AIDS information to individuals. Agencies are usually most interested in policy, program, and funding information, as well as easy-to-learn email and other facilities. Also, John Laird noted, "The basic points for me are that we are designed to serve AIDS service agencies and provide an across-the-board array of information in an easy-to-use system... One of the strengths of the whole project is the capacity building of AIDS organizations. They are trained as electronic publishers, adding a capability that none presently has... When the grant runs out, this capacity will be what carries the network -- as it is these organizations, not HandsNet, that place the information online. Also, one of the strengths of HandsNet is the ability to provide toll-free support and phone tours to new groups coming online to build their knowledge." HandsNet has a point-and-click "graphical user interface," which many people prefer. AEGIS will soon have a graphical user interface. [Our own view is that if a system is well designed for its users, a graphical interface is a matter of personal preference, not a fundamental advance.] Both HandsNet and AEGIS have excellent keyword search facilities. Our biggest concern is that the cost of HandsNet, over $400 per year for a single account no matter how little it is used, may limit the AIDS/HIV Forum to better-funded agencies. In theory, this cost can be shifted from other expenses such as overnight express, faxes, and periodical subscriptions. And email uses staff time very efficiently; one just types a message and off it goes, without the need to prepare an envelope, or feed papers through a fax. But local, underfunded agencies that rely mainly on volunteers may not be able to justify the expense this way. There are now projects in several cities to develop free AIDS computer systems with email and full Internet access. These may become the communication medium for smaller agencies, as well as individuals. If a two-tier system develops, it could increase the problem of well-funded, well-connected agencies and professionals talking mostly to each other, losing contact with the grassroots support they need to be successful. Computer communication is changing very rapidly, and no one knows which software will prove useful in the future. Therefore, experimentation is necessary; there is no such thing as an ideal choice today. We strongly support both the HandsNet AIDS/HIV Forum, and AEGIS, and other computer communication systems now being used or developed for AIDS work. These are the practical choices today, and no one knows what will ultimately prove best. For More Information (1) For more information about the HandsNet AIDS/HIV Forum, call John Laird at HandsNet, 408/257-4500. Or send email to him at hn3187@handsnet.org. (2) For more information about AEGIS, you can log on without prior arrangements by calling its central hub in San Juan Capistrano, California, 714/248-2836 (modem). Or send email to Sister Mary Elizabeth at mary.elizabeth@aegis.hivnet.org, or call her at 714/248-5843. AEGIS also has "mirror" systems in a number of other cities, allowing free access with a local call; you can get a current list by logging on to the central system at the number above. We will not list the many AIDS-related databases offered by AEGIS, because this system deserves an article of its own. AEGIS has done excellent work with a small budget; we urge those who can to send contributions, which can be mailed to: Sisters of St. Elizabeth, ATTN: AEGIS Network, P.O. Box 184, San Juan Capistrano, CA 92693-0184. Make checks payable to Sisters of St. Elizabeth (tax deductible), with AEGIS in the memo field. (3) For additional pointers to AIDS information available by computer, see the 14-page "Guide to Selected AIDS-Related Electronic Bulletin Boards and Internet Resources," published by the U.S. CDC National AIDS Clearinghouse. To order a copy, call 800/458-5231; to get through the voicemail, press '1', then '2', then '3' (this may change). Ask for publication number B-313. ***** Threats to Ryan White, AIDS Funding: Call for Information On November 22, the WASHINGTON POST mentioned a Republican proposal for "dismantling the Ryan White program to care for AIDS patients (and) reexamining the Americans with Disabilities Act." The San Francisco-based Mobilization Against AIDS called the reporters, but they could not identify the staff person they talked to, nor the member of Congress for whom that person worked. The Ryan White CARE Act supports clinics, drug assistance programs, counseling, and many other kinds of services, in heavily impacted cities and states. In some areas, it is the only AIDS funding available. It has had strong bipartisan support in Congress. Its current five-year term will expire in September 1995; until it is reauthorized, organizations cannot apply for new funding, threatening continuity of service. If you know of any threats of major funding cuts in AIDS research, prevention, or care, which have not already been widely publicized -- or, on the other hand, about proposed improvements in medical research and drug development, such as reducing the "entry cost" for innovative treatment ideas to reach the market -- please contact AIDS Treatment News, 800/TREAT-1-2, or P.O. Box 411256, San Francisco, CA 94141, or aidsnews@igc.apc.org. ***** 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 fax: 415/255-4659 Internet: aidsnews@igc.apc.org Editor and Publisher: John S. James Reader Services and Business: 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 1994 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.