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AIDS Treatment News
December 5, 1997

Contents:


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Viral Immunology Advances Suggest Treatment Strategies

by John S. James


A study published November 21 in Science1 is generating considerable scientific interest, and suggests possible treatment strategies for both early and more advanced HIV infection. While this study itself is one small building block among a number of important advances toward the understanding of how the body first controls HIV infection but later usually fails to do so, its publication seems to mark a time of change toward integration of virological and immunological approaches, away from the relative neglect of immunology and domination of HIV research by virology.

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The picture emerging from this and other studies is that in most cases of HIV infection, the T-helper cells which respond specifically to HIV (and help to bring down the very high viral load which develops during primary HIV infection) seem to be lost or stop working early in the disease process. The new study examined long-term nonprogressors, and found that in them, this specific T-helper response against HIV remained strong. In other persons with HIV who were tested, this response correlated strongly with low viral load (much more strongly than CD4 count correlated with viral load), suggesting that specific T-helper response to HIV is important in the body's control of the virus. Why the specific anti-HIV activity is lost is unknown; it is possible that the cells which recognize HIV are activated and therefore easily infected at the time of high viral levels during primary infection.

Two practical consequences have been suggested by a number of researchers:

(1) Effective antiretroviral treatment early enough -- probably during primary infection with a regimen including protease inhibitors -- may allow the specific anti-HIV responses to be preserved, as they seem to be in long-term nonprogressors. Early experience from treatment of patients during primary infection supports this possibility.

(2) Later in HIV disease, antiviral treatment which results in undetectable viral load generally does not lead automatically to the return of these specific anti-HIV T- helper cells. However, there is reason to believe that they still could be induced by vaccination while the infectious virus is suppressed by antiretrovirals. Several approaches -- killed-virus vaccine, certain HIV antigens produced by genetic engineering, or DNA vaccines -- are feasible to try now.


References

  1. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, and Walker BD. Vigorous HIV-1-Specific CD4+ T Cell Responses Associated with Control of Viremia. Science November 21, 1997, volume 278, pages 1447-1450. Also see commentary in the same issue, "How does HIV overcome the body's T cell bodyguards?," by Michael Balter, pages 1399- 1400.


New Meeting on Immune Surrogate Markers

Baltimore, January 9-11


A new meeting on "the identification of meaningful surrogate markers of immune reconstitution" will be hosted next month by the Institute of Human Virology and the University of Maryland Foundation. This conference has been called on short notice, so help is needed in getting the word out. The steering committee of about 20 leading researchers includes Larry Fox, Robert Gallo, Alan Landay, Michael Lederman, Robert Redfield, Nara Sarver, Fred Valentine, and Bruce Walker. Cosponsoring organizations are the Harvard AIDS Institute, Pacific Oaks Medical Group, Project Inform, and Search for a Cure.

The "First Annual Immune Function and Surrogate Markers: Setting the Goal Line" will take place at the University of Maryland, Baltimore campus; rooms have been reserved at the Hyatt Regency Baltimore. Conference registration is $200 for academic registrants, $300 for corporate. Registration is requested if possible by December 15.

For more information, including the program and the registration form, contact Jeffrey Meshulam, Institute of Human Virology, 410-706-8614, fax 410-706-1952, email ihvinfo@umbi.umd.edu.


FDA Approves New Kind of Lymphoma Treatment

by John S. James and Greg Dubs, Ph.D.


On November 26 the FDA approved rituximab (Rituxan), a monoclonal antibody, for treating certain kinds of non- Hodgkin's lymphoma. While not a cure, it appears to be an important treatment advance; also, it is the first monoclonal antibody approved to treat cancer, at least in the U.S. It has not yet been tested in persons with HIV, but such trials are now being organized. The official approval is only "for the treatment of patients with relapsed or refractory low- grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma"; however, the drug is likely to be useful for some other lymphomas as well. (HIV-related lymphoma is usually high grade.)

Rituximab works by killing B-cells, both normal and cancerous; the body can replace the normal cells after several months. B-cells produce antibodies for fighting certain infections, but no increase in infections has been found so far. Side effects of this treatment are usually much less than with conventional chemotherapy.

In one trial in 166 patients with relapsed or refractory low- grade non-Hodgkin's lymphoma (those with large tumors were excluded from this study), 6% of the volunteers had a complete response, and 42% had a partial response.1 In another trial, 46% of patients responded to rituximab treatment after they had failed conventional therapy; of the 17 responders, 14 had partial remission and three had complete remission.2

Combination use with chemotherapy seemed to work especially well in another trial.3 Forty volunteers with low-grade lymphoma were entered, 80% of them with no prior therapy. Of the 35 who completed the treatment, the response rate was 100% (60% complete response and 40% partial response). Of the other five, two did not receive treatment, and the three others had a partial response.

In addition, there is laboratory evidence that the antibody may re-sensitize tumor cells that had become resistant to the chemotherapy.4

There is concern that rituximab might be dangerous if used as initial therapy if there is a high tumor burden, because of possible toxicity from killing too many B-cells at once. To avoid this, other treatment may be used first to reduce the tumor burden. There is interest in not waiting for the chemotherapy to fail (as the officially approved indication suggests), but instead using the antibody sooner.

The approved rituximab treatment is four doses over a 22-day period -- because this is what was used most in the important clinical trials. Unfortunately, the drug price to physicians for the four-course treatment is about $11,000; it is expected that insurance will pay in some cases, but be a problem in others. Rituximab was discovered by IDEC Pharmaceuticals Corp., and developed by IDEC and Genentech Inc. It is being marketed in the U.S. by Genentech.

Genentech has established a toll-free number to help with reimbursement problems, and has an Uninsured Patients Assistance Program to "provide assistance to patients whose physicians recommended treatment with Rituxan, regardless of the patients' economic or insurance status." We do not have the phone numbers or additional information at press time.

A newly formed Lymphoma Action Group began shortly before the approval. It will be working especially on increasing access to the drug, particularly for persons with HIV or others with high-grade lymphoma (who may need the most help with access, since the official indication is for low grade). To contact the group, leave a message at 415-790-5716.


References

  1. Rituxan package insert, November 1997.

  2. Maloney DG, Grillo-Lopez AJ, White CA and others. IDEC- C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood September 15, 1997, volume 90, number 6, pages 2188- 2195.

  3. Czuczman M, Grillo-Lopez AJ, White CA and others. IDEC- C2B8/CHOP chemoimmunotherapy in patients with low-grade lymphoma: clinical and BCL-2 (PCR) final results. Blood November 15, 1996; volume 88, number 10 (supplement 1), abstract #1799.

  4. Demidem A, Lam T, Alas S, Hariharan K, Hanna N, and Bonavida B. Chimeric Anti-CD20 (IDEC-C2B8) Monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biotherapy & Radiopharmaceuticals 1997; volume 12, number 3, pages 177-186.


Major AIDS Institute Inaugurated in San Francisco


On December 1 the University of California San Francisco (UCSF) officially inaugurated the AIDS Research Institute, "the largest AIDS initiative anywhere outside of the National Institutes of Health." This effort brings together all existing AIDS programs at the University, and has a strong focus on multidisciplinary research.

"The next generation of answers requires a deeper level of collaboration," said Thomas Coates, Ph.D., director of the Institute, and professor of medicine, epidemiology, and statistics at UCSF. "The important answers will come at the interface of the sciences. It's clear we cannot answer clinically important questions without bringing people together."

The AIDS Research Institute will provide "both financial and practical support for a broad range of initiatives, including vaccine research, development of new therapies, studies of transmission dynamics, prevention science, AIDS policy and ethics research, a new clinical virology and immunology lab, and international and community studies. It will also provide the mechanism for meetings of scientific minds through town hall forums, peer review sessions, focus groups and 'targeted action groups,' in which a dozen or so researchers will meet to plan multidisciplinary studies."

The executive committee consists of Haile T. Debas, M.D. (Chancellor and Dean of the School of Medicine at UCSF), Margaret A. Chesney, Ph.D., Thomas J. Coates, Ph.D., Warner C. Greene, M.D., Ph.D., John S. Greenspan, B.Sc., B.D.S., Ph.D., Jay A. Levy, M.D., Paul A. Volberding, M.D., and Diane W. Wara, M.D.

For more information, see the UCSF AIDS Web site, http://hivinsite.ucsf.edu/ari


Protease Inhibitor Information

FDA Fact Sheet Available


Basic information on the four HIV protease inhibitors approved in the U.S. has been published in a fold-out brochure by the U.S. Food and Drug Administration, entitled The Protease Inhibitor Backgrounder. Copies are available without charge.

The current edition, last updated in October, includes information on dosage, relation to food, storage requirements, warnings and precautions, most frequent adverse effects, pediatric use, medications that should not be used with each protease inhibitor, and drug interactions requiring dose adjustment. There is also a list of suspected interactions, especially with ritonavir (suspected due to the metabolism of the drugs, although clinical trials to check for these interactions have not been done), and advice on reducing risk if these combinations must be used. Some information on dosing when using two protease inhibitors simultaneously is provided in this section.

The reading level is appropriate for medical staff or informed patients.

Comment: This authoritative and non-promotional publication will help patients understand their options, and also help assure that instructions provided with protease-inhibitor prescriptions are correctly understood. Failure to follow instructions for use of drugs is a major problem in medicine, and the consequences are especially serious with HIV treatments, particularly protease inhibitors. Sometimes the instructions are not followed because the patient never understood them. And sometimes instructions are wrong, as when drugs are combined incorrectly. This brochure will help assure that patients understand the instructions, and may bring potential errors to the attention of medical staff.

The Protease Backgrounder is available on the World Wide Web under FDA's HIV/AIDS Therapeutic Index, found at: http://www.fda.gov/oashi/aids/piindex.shtml, or by calling the FDA Office of Special Health Issues at 301-827-4460.


Protease Inhibitor Failure Trial

Combination 1592, 141W94, and Efavirenz


Persons with detectable viral load despite treatment with combination therapy which includes a protease inhibitor are receiving a combination of three new antiretrovirals, in a phase II multicenter study organized by Glaxo Wellcome and now being conducted in nine U.S. cities. As this issue of AIDS Treatment News went to press with an announcement, we learned that the trial as originally designed is oversubscribed, although it started recruiting only in November. There has been discussion about possibly expanding the number of patients, but no decision has been made.

Volunteers are 13 or older, with viral load over 500 copies despite treatment including a protease inhibitor. They must have been receiving the same protease inhibitor(s) for the most recent 12 weeks and continuing until the start of the study medication. They must not have used 1592, 141W94, or efavirenz (also called SUSTIVA, or DMP-266) before; also, certain other treatments must not have been used within 30 days. There are other criteria, including no AIDS-defining opportunistic infection or malignancy except Kaposi's sarcoma, and a negative pregnancy test for women.

This is an open-label study, meaning everyone receives the three medications. There is no randomization or control group. The goal is to study the antiviral activity of the drug combination, and also its safety and tolerability, when existing regimens do not fully control the virus.

Each of these drugs has side effects. For each one, rash is the most common reason for which the drug has had to be discontinued.


New AIDS Bookstore on World Wide Web

by John S. James


Immunet, a nonprofit HIV and AIDS education organization which runs the Web site http://www.immunet.org, opened an online AIDS bookstore on December 1. This is a valuable resource, both for obtaining AIDS books which otherwise may be hard to find, and as a free research tool to see what is available. As of December 2, this site lists 3,059 AIDS books which can be ordered online, and includes reviews of 547 of them.

This site is also noteworthy as an example of a kind of online business and community structure which we believe will become much more important over the next few years, and which is likely to have other uses in AIDS, including buyers clubs and possibly pharmacies.


How to Use the Site

From the Immunet home page, select the Online Bookstore; most users will then search for books by one or more keywords. As a test, we entered "nutrition" and found 36 books on AIDS and nutrition; a search on "pathogenesis" found 27 books. Most of the books we found have reviews available. You can also search for author by entering a last name as a keyword.

For each book, you can read the review if any, and can obtain ordering information, including price and an estimate of how long it will take to be shipped (usually a few days, but if delivery is likely to be delayed, you know that before placing the order).

The reviews are provided by the AIDS Book Review Journal, of the University of Illinois. Orders are processed and shipped by Amazon.com, a large and well-known online bookstore.

It is no accident that most of the books which were found in our searches do have reviews. This is because the search will examine the title, and also the review if there is one; and it is more likely that the exact word being sought will occur somewhere in a lengthy review of a relevant book, than in the much shorter title. The "nutrition" search, for example, found 24 books that were reviewed and 12 that were not; all of the books that were not reviewed had "nutrition" (or "nutritional") in the title, or they would not have been found. This system works for most users, because presumably the most important books are likely to be reviewed, and yet the others can be found as well.

As of December 2 the list of non-reviewed AIDS books is preliminary and appears to have been computer generated. Suggestions for improvement -- especially books that should be listed but are missing -- can be sent to Gary Schaff, gschaff@immunet.org, or to Tony Brooks, tbrooks@immunet.org.


Comment: Community Building

A major key to successful Web sites is community building. Large merchandising organizations are seldom good at that. On the other hand, community-based or specialized interest groups are seldom effective at running a large business efficiently (processing orders, shipping books, building relationships with suppliers, etc.); this is not what they want to do. Unlike other media, the World Wide Web allows orders to be passed from the community organization to the merchandiser with zero cost and zero delay.

All the parties can benefit. The community group earns a referral fee for orders it generates (5 to 15%, according to Immunet's press release), without having to process or ship the orders -- creating a fundraising tool for organizations. The merchandiser receives orders with guaranteed profit, as there is no up-front cost for advertising or promotion. Customers can use a site built around their needs and interests, and still receive discounts and pay no more than if they placed their orders elsewhere.

Ultimately the negotiating leverage rests with the community organizations, not the merchandisers, even when the latter are much larger entities. For as the online market develops, there will be a number of competing merchandisers, all offering about the same prices and services. A community group can take its business to any of them; there is no "Microsoft effect," no natural monopoly based on a mutual benefit in everybody using the same system. But while merchandisers are generic, each community is unique; whoever brings the people has the controlling advantage. This dynamic can provide some antidote to the increasing centralization and remoteness of modern institutions.

We believe that this kind of arrangement could be important for AIDS or other buyers' clubs -- which could offer huge selections at low prices by referring fulfillment of routine orders to selected commercial suppliers, while shipping the most specialized orders themselves.


Revised Federal Antiretroviral Treatment Guidelines


Guidelines for the Use of Antiretroviral Agents in HIV Infected Adults and Adolescents, the influential guidelines of a panel organized by the U.S. Department of Health & Human Services, were first published in draft form on June 19, 1997. A revised version dated November 5 is now available at a number of sites on the Web.

The new Web site of the University of California San Francisco, http://hivinsite.ucsf.edu/, has links to the new draft, both the official release with the original graphics, and also in a Web format more convenient for many users. In addition, it has links to about a dozen other major AIDS- related treatment guideline documents.

A review of the changes, by Edward King of AIDS Treatment Update in London, is available at http://aids.miningco.com/library/weekly/aa111697.htm


FDA Reform Signed into Law

by John S. James


After three years of attempts, Congressional efforts to change the law under which FDA operates achieved bipartisan consensus. The result, the FDA Modernization Act of 1997, was signed into law by President Clinton on November 21. Major provisions are:

  • "Fast track" review for the most important drugs -- those "intended for the treatment of a serious or life-threatening condition and [which demonstrate] the potential to address unmet medical needs for such a condition." Drug companies must apply for fast-track status -- which they may do when they apply for an IND (permission to test the drug in humans) or any time afterwards -- and then the FDA must decide within 60 days whether to grant it. The fast-track section is closely based on procedures the FDA has already developed and used for accelerated approval of some AIDS and cancer treatments. The new law encourages the development of new surrogate markers of drug efficacy; however, fast-track status can apply whether or not surrogate markers are used.

  • Allowing drug companies to promote "off label" drug uses by sending peer-reviewed articles to physicians; this is probably the most controversial major provision of the law. Also, companies will be allowed to make economic claims to HMOs (health maintenance organizations) -- but not to patients or physicians -- without running controlled clinical trials, as previously required, which would often be impractical or unethical.

  • Changing the mission of the FDA. In addition to protecting the public from unsafe drugs, its mission now will also be to speed research, innovation, and access to care.

  • Renewing PDUFA (the Prescription Drug User Fee Act), which allows the FDA to charge companies for reviewing their drugs, and use the money to hire more reviewers so that approval decisions can be made more quickly. PDUFA has been a huge success and is universally supported -- especially by the companies which have to pay the fees, since the advantage of earlier approval greatly outweighs the cost. PDUFA would almost certainly have been renewed in any case, but was delayed by the politics around other aspects of the bill.

  • Legislation on compounding of drugs by pharmacists or physicians. According to Julie Gossman of Emord and Associates, a law firm in Washington D.C., the new law regulates the current practice of compounding, and should not cause major changes there.

  • Substantial legislation in other areas, including medical devices, and health claims for foods.

Also, there can always be "sleepers," inconspicuous phrases which are added by special interests and become law by surprise. Today it is common that neither the public nor members of Congress know exactly what is in a major bill when the final vote is taken.

The bill will probably not fix the very serious delays early in the development process, when an experimental drug is first entering clinical trials. This issue unfortunately dropped out of the discussion early on, and has never received sustained national attention. It is hard to build political momentum around events which occur early, before a compound has become a therapeutic option for people.

Most AIDS organizations and activists have not been involved in the discussion and debate about this bill. Of those who were involved, most were strongly opposed; they worked through a new group called the Patients' Coalition. One organization, the Log Cabin Republicans, strongly supported the bill.


Comment

We doubt that the new law will have a major near-term impact on AIDS drug development, since the fast-track provisions mostly legislate what the FDA has done already for the most clearly important AIDS drugs. The law should, however, encourage more attention to surrogate markers for drugs other than antiretrovirals -- for AIDS and other serious illnesses as well.

The other big change, allowing limited promotion of off-label uses, has become framed as a debate between consumer protectionists and industry. ("Off-label" use means that a drug approved by the FDA for one use is prescribed by doctors for another purpose. It has long been recognized as legal and proper for physicians to do this; however, pharmaceutical companies could not promote such uses. They could give doctors peer-reviewed articles if asked, but could not take the initiative to provide them, even to a doctor.) Opponents say that the new law will allow companies to profit from uses not proved safe and effective, will remove incentive for companies to get their drugs approved for new uses, and will result in more prescriptions not being covered by insurance. They fear that companies could start promoting new uses just by announcing that they will file an IND, doing the minimal paperwork, and repeating the process whenever necessary; the law requires an IND (so that the offlabel uses will be researched and, if proven, come onto the label), but cannot stipulate that the IND be a credible one. On the other side, industry sees the new revenue streams from off-label uses as particularly important to small biotech companies which can only afford to go for one approval at a time.

What needs more attention is the apparently large number of people with serious health problems which could be successfully treated with available drugs, but who are never told that by their doctors, even though credible evidence has been published. The number of cases of people who learn by happenstance, through friends, newsletters, or noticing a story in the news, suggests that there are probably hundreds of thousands, possibly millions, who could benefit substantially from known off-label uses of available drugs, but who are not receiving that help today. Most doctors will not bring up treatments which are outside the mainstream and are not promoted.

In recent years the FDA has made it easier for companies to get these new indications approved, which is commendable; but many valid uses will never be submitted for approval (with or without the new legislation), especially if they are inexpensive and therefore will not generate revenue to cover development costs. The new law may have created the first institutional incentive to bring such treatments into use.

Hopefully industry will use this new power responsibly -- and medical and public-service organizations will be ready to call companies on any abuses.


Press Must Register Now to Cover February Retroviruses Meeting

December 29 Deadline

by John S. James


Next year's major AIDS research conference in the United States will be held at the Sheraton Chicago Hotel, February 1-5, 1998; reporters must register over a month in advance in order to be admitted. On December 1 the conference secretariat released a "Press Registration" memo with information about the conference, and a "Press Registration Information" sheet with specific instructions. Due to the delayed notice and the importance of the meeting, we include the instructions here:


"5th Conference on Retroviruses and Opportunistic Infections, Press Registration Information:

"Press registration applications will be reviewed by members of the Scientific Program Committee. Applications from community newsletters will be reviewed by the Community Liaison Subcommittee. All press must preregister. There will be no on-site registration.

"Who May Register

"Representatives from the following media may register as press:

  • general-circulation newspapers or magazines

  • general-circulation medical/healthcare publications

  • broadcast news media

  • community-based newsletters

"Medical communications companies, financial press, biotechnology newsletters, public relations firms, and noneditorial staff such as publishers and representatives of sales, marketing, or advertising departments are not eligible for press registration. Individuals, agents, or contractors providing coverage for or being sponsored by industry may not register as press.

"Freelance writers should provide proper credentials as well as a letter of assignment from a publication. Unassigned freelance writers may not register as press.

"Any publication, supplement, or electronic product devoted exclusively to the coverage of the conference must have prior written approval of the Scientific Program Committee (e.g., meeting highlights, on-line conference proceedings/reporting, audio conferences, etc.). Media campaigns at the conference and distribution of company-sponsored press releases (both at the conference and off-site) are not permitted preceding or during the meeting dates.

"How Many May Register

"Press registration is limited to 180. Up to two reporters per publication, publication group or electronic news-media service may register as press. Applications for a second reporter will be considered after all other requests have been received, and registration privileges will be provided if the limit has not already been reached. Additional badges (above the allotment of 2 per media outlet) providing admittance to press conferences will be available for television crews.

"How To Register

"Requests for press registration should be submitted (preferably on the attached registration form) along with the materials listed below:

"Press who have been credentialed for the conference in the past 2 years should include:

"1. a letter from the editor (or masthead with reporter's name listed)

"2. sample of a recent article (preferably from the last Retrovirus Conference, demonstrating previous coverage, and with a byline)

"Press who have not registered for previous Retrovirus Conferences should include:

"1. a letter from the editor

"2. copy of one recent article (published within the past year and preferably with a byline)

"3. sample publication

"Send the above materials to:
Press Registration
Retrovirus Conference Secretariat
211 N. Union St., Suite 100
Alexandria, VA 22314
(703) 684-4876 phone / (703) 684-4841 fax

"Deadline

"The deadline for press registration is December 29, 1997 (or until the press block has filled, whichever occurs sooner). All applications will be handled on a first-come, first- served basis. Within two weeks of receipt of press application and after press credentials have been reviewed and approved, a confirmation letter and housing information will be sent. A press kit and final program and abstracts book will be sent two weeks prior to the Conference to all preregistered press."


Note: There is no registration fee for press. But persons cannot register for this conference just by paying a fee; they must be a member of an allowed category, such as one of the press categories above. It is unclear where gay newspapers and perhaps certain other media will fit, and this may be a problem; our understanding is that "community-based newsletters" are expected to be AIDS-specific.

The 5th Conference on Retroviruses and Opportunistic Infections "is sponsored by the Foundation for Retrovirology and Human Health and is held in scientific collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Centers for Disease Control and Prevention (CDC)." The secretariat is the Westover Management Group, 703-684-4876, fax 703-684-4841.


Correction:
FORTOVASE Information Number for Patients in Washington D.C. Area


Our last issue published two Hoffmann-La Roche numbers for patients seeking information about FORTOVASE, the new saquinavir formulation which was approved by the FDA on November 7. The national toll-free number was correct; but the Washington D.C. telephone number for local patients only is not in service. Callers in the Washington area should use the national number, 800-910-4687, Monday through Friday 9:00 a.m.- 6:00 p.m. Eastern time.


December Deadline for Charitable Giving and Tax Relief

by John S. James


The traditional season for giving is also the best time for those who have done well financially during the year to make charitable contributions which can reduce their taxes. This is because the year's financial picture is mostly in view, yet there is still time to contribute within the 1997 calendar year. Successful investors may find particular advantage in donating appreciated securities, since they can avoid capital gains tax while also increasing their charitable deduction.

One charity we suggest is AIDS Treatment News Associates, 584-B Castro Street, San Francisco, CA 94114. A 501(c)(3) organization, ATNA reimburses free subscriptions for persons who cannot afford to pay for AIDS Treatment News. Contributions to ATNA relieve us of a serious financial burden, since AIDS Treatment News has never turned people away but sends free subscriptions at our expense when necessary. And to guard our independence we do not accept pharmaceutical-company contributions, even for charitable purposes.

The changing epidemic during the last several years has meant that more people who need and request this information cannot pay even the cost of printing and mailing their newsletter; we have become payers of last resort. We need assistance to avoid spending more and more time working around financial constraints, time we could better devote to our work.

For more information, contact me at AIDS Treatment News, or at 415-255-6259.



ISSN # 1052-4207

Copyright 1997 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.




  
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