Subject: AIDS Treatment News #116 Date: Dec 09 1990 (653 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& J O H N J A M E S writes on A I D S &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& copyright 1990 by John S. James; permission granted for non-commercial use. AIDS TREATMENT NEWS Issue #116, December 7, 1990 phone 415/255-0588 Contents: [items are separated by "*****" for this display] ddI and ddC Approval Effort -- Interview with Martin Delaney Opportunistic Infection Project Launched by ACT UP/NY: "Countdown 18 Months" Computerized Clinical Trials Locater Opens in San Francisco New DNCB Study In Memoriam: Temple Minner, David Smyth San Francisco: CARE Bill Hearing, December 11 Resource List: ACT UP Affiliates, Buyers' Clubs, and PWA Coalitions ***** ddI and ddC Approval Effort -- Interview with Martin Delaney by John S. James Martin Delaney, co-founder of Project Inform, has been actively involved since August in the effort to obtain rapid evaluation and, hopefully, approval of ddI and ddC. We asked him to outline what is happening in this effort. Before working full time in AIDS, Mr. Delaney taught negotiation and other business skills to corporate teams. Recently he has communicated extensively with the researchers studying ddI and ddC, and with other experts from the sponsoring pharmaceutical companies, the FDA, the National Institutes of Health, and activist organizations. JJ: You are optimistic on early approval. What are the reasons for optimism? MD: I have had extensive meetings with the parties -- the FDA, the researchers, the companies, and other activists. There are some uncertainties about how the data will be evaluated, but there is a clear commitment on the FDA's part in making this process happen. The discussions are about how they can make it happen, not whether. The question is, how can we evaluate the data in this circumstance, and make a scientific case that what we are seeing is predictive of the usefulness of the drug? The issues are not unique to ddI or ddC. These are broader issues for all AIDS drugs in the near future. We will not have placebo studies, so we must find ways to make comparisons to existing AZT data, and to a better picture of the recent natural history of AIDS since the beginning of pneumocystis prophylaxis. If these issues did not come up now for these drugs, they would come up for whatever drugs are next. There are scientific hurdles, but there is also a strong commitment to clear these hurdles, to find a scientifically valid way to do it. There are no simple answers here. The simple answers have already been rejected by FDA. For example, they do not feel that T-helper increases -- even for a longer period than produced by AZT -- is, by itself, adequate proof of the drug, unless it is corroborated by other data. But others hotly dispute this view, arguing that T-helper increases alone should be enough. The FDA does not want to be the obstacle; it recognizes the critical urgency of making the two drugs available. So they are saying that they want a joint decision, a collective decision- making process to explore all these issues, with scientists in other research and development agencies -- for example, the National Cancer Institute, and the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases, as well as activist experts -- on how the NDA (New Drug Application, with the detailed data on the drug) should be submitted. The FDA has agreed that it is safer politically to seek expert consensus in this way; if it made the decision alone without consultation, it would be highly vulnerable if something went wrong. In the FDA's view, this decision is a watershed event. We do not want them to make it alone. JJ: The biggest questions seem to revolve around what constitutes proof of efficacy. MD: Absolutely. The debate will hinge partly around the meaning of drug-induced T-helper increases. Statisticians are finding that T-helper counts definitely associate with survival outcome -- especially that the risk is greater when the count falls below 50. The tougher question is, if the T-helper counts are so predictive, does increasing the counts by use of a drug predict increased survival, as a higher count does in the natural history (without treatment)? Most researchers instinctively believe it does [that an antiviral which increases T-helper count probably does improve survival]. But the FDA argues that no one has yet proven this point. Recent statistical analysis suggested that the benefits of AZT are greater than what would be predicted simply by the T- helper increase. Why that is so is unclear. The T-helper count may not tell us all we need to know about the immune system; the benefit of AZT may be greater than this count alone would suggest. None the less, others argue that increased T-helper counts are one useful predictor of a drug's efficacy. The National Cancer Institute, for example, says that in all its studies, any antiviral drug which has kept the T-helper count above 50 seems to keep people alive. In the NCI studies, only one patient who remained above 50 has died in the last four years. Samuel Broder, M. D., director of the NCI, strongly believes that this data alone validates the usefulness of drug- induced T- helper increases [as an indicator of clinical or survival benefit from the drug]. The long-term clinical picture, as measured by the number of opportunistic infections or by survival, is harder to evaluate than people would like, because the easiest point of comparison is the old AZT studies. And most of those were done without pneumocystis prophylaxis. So the FDA is reluctant to use them for comparison, arguing that more recent data includes other variables besides the drug. So now Bristol-Myers is collecting data from several major clinical centers in the country -- not just ddI data, but also case-history data from patients not given ddI, to get a better picture of the natural history of AIDS with pneumocystis prophylaxis. Perhaps this data can be used as a valid comparison; but of course much work is required. Another outcome which FDA will consider will be overall clinical improvement, such as weight gain, or Karnofsky scores (a rating of overall health). If you put each of these pieces together, and if they are coherent, I think there is no question that FDA will grant the approval. But they do not want to approve the drugs on T-helper counts alone, without this other data. There should also be some input from virology markers. Plasma viremia data (measuring the amount of virus in the blood) should be available by January. If you keep your eye on all of these pieces of the picture, you don't get nervous with every new rumor that sweeps part of the country. JJ: What else is at stake here, beyond the short-term availability of ddI and ddC? MD: A great deal is at stake. If the FDA cannot find a way to accept this kind of data as proof of drug effectiveness, it will have no choice but to demand the re-use of survival as the sole endpoint in future studies. In other words, we test the drug until some of the patients die. And this would require a return to the routine use of placebo controls. We cannot allow this to happen. JJ: If a drug is known to be an antiviral, known to be effective against HIV at concentrations reached in the body -- and if there is no reason to suspect that the drug raises T- helper counts directly -- then if T-helper counts consistently go up when the drug is given to persons with HIV, it seems hard to explain that effect other than by an antiviral action of the drug. Average T-helper cell counts do not rise spontaneously, without treatment, in any known group of persons with AIDS or HIV. It is hard for us to understand waiting months or years for conclusive proof of benefit, after it is already clear that a drug does show a substantial antiviral efficacy in patients. Usually the FDA's Antiviral Advisory Committee meets for only a day or two, with little or no staff support. How can it possibly give the ddI and ddC decisions the attention they deserve, in view of the extensive data about these drugs, and the major issues regarding interpretation of the data? MD: The committee probably could not do this by itself. Therefore, it will be assisted by other leading researchers brought in as consultants, who have expertise on these particular drugs. A special meeting of the nation's top experts, probably in early February, will seek a consensus on whether these drugs should be approved. In practice, this process must go through the existing structure of the FDA advisory committees. JJ: There has been concern that neither company (Bristol- Myers for ddI, or Hoffmann-La Roche for ddC) has yet submitted its NDA (New Drug Approval application) to the FDA. MD: The companies do seem to be on schedule for submission of that data. It would be a mistake to submit it too early, before they knew what the FDA wanted of them. I have reassurances that Bristol-Myers will be submitting its NDA shortly after the advisory committee meeting, probably in February. Hoffmann-La Roche has not yet looked as closely at its data, but they have said that they intend to submit their NDA early in 1991. JJ: What timetable do you see for a decision on approval of these drugs? MD: The advisory meeting date has not yet been set, but should be in early February. I see at least one of the NDA applications coming in about a week after that time. Then it would take at least 30 days for the FDA to analyze the data; they may have to ask more questions of the company. All things considered, I think it's a do-able target to get both drugs out by March of 1991. Anything much beyond that, and we should raise the temperature politically. The consensus building is most important, because it will set a standard of how we look at these urgent approvals in the future. We do not ask the FDA to decide all by itself in an ivory tower. Instead, we want a collective decision with input from all the people who are working in this field. Note: On December 19, a multi-city press conference will explain the movement for early ddI and ddC evaluation. Project Inform and other organizations involved in this issue will take part. As of this week, 35 organizations have signed a consensus statement circulated by Project Inform (with much help from ACT UP/Golden Gate and Mobilization Against AIDS), calling for urgent review of ddI and ddC. Also, the Community Consortium, a medical group representing almost all of the physicians who have an HIV practices in San Francisco, issued a separate statement urging expedited review of the data on these drugs, with a decision on licensing as soon as possible. In addition, at least 25 members of Congress have signed a letter to the FDA by Congresswoman Barbara Boxer (D-Greenbrae, CA) urging immediate review of ddI and ddC. ***** Opportunistic Infection Project Launched by ACT UP/New York: "Countdown 18 Months" by Denny Smith Most of the opportunistic infections identified with AIDS are considered treatable to some degree. But in nearly every instance, the treatments are limited by their side effects or their unreliability for obtaining a consistent response, especially against recurrent infections. Research into better drugs for opportunistic infections has never approached the intensity of attention or funding afforded to research in primary HIV infection. A campaign to find safer and truly definitive treatments, within a year and a half, for five of the most lethal AIDS- related infections has been inaugurated by ACT UP/New York. This project, dubbed "Countdown 18 Months," was formally launched November 12 during the latest session of the AIDS Clinical Trials Group (ACTG). The idea was first proposed by Garance Franke-Ruta, and developed by her with fellow members of ACT UP/New York's Treatment and Data Committee. Motivating the campaign are two well-founded assertions: * A dramatic advance in controlling HIV progression is inevitable, but it may develop too far in the future to prevent many currently asymptomatic seropositives from progressing to symptoms. And it is not of immediate use to thousands of people already battling secondary opportunistic infections. * The resources now exist with which to replace the haphazard "aim and wince" handling of opportunistic infections, and 18 months is not an unrealistic span in which to mobilize these resources. A crucial condition for the success of this project will be the development of effective working relationships with persons in pharmaceutical companies and government agencies. The five infections targeted by Countdown 18 Months are pneumocystis pneumonia, CMV retinitis and colitis, toxoplasmosis, MAI, and the fungal infections -- cryptococcosis, histoplasmosis and candidiasis. A 44-page planning document distributed by ACT UP/New York describes the rationale and goals of the plan; it also includes an in-depth look at existing treatments for these infections, experimental treatments now being tried, ways to obtain experimental treatments, reference for more information, and a select contact list of persons involved in AIDS research. Requests for copies of The Countdown 18 Months Plan can be sent, with a small donation if possible, to ACT UP/New York, c/o Countdown, 135 W. 29th St., 10th floor, New York, NY 10001. Information regarding how to work on the Countdown project can be obtained from Garance Franke-Ruta, 212/532-0280 or 212/675-5170, or from Derek Link, 212/529-2368 or fax, 212/529-5997. ***** Computerized Clinical Trials Locater Opens in San Francisco by John S. James A new service at Davies Hospital in San Francisco will search a database of local clinical trials and prepare a printout with description and contact information for all trials for which a patient may qualify. Anyone with AIDS or HIV may use this service. At present, only trials in the San Francisco Bay Area are listed; however, the system could be customized by medical or research institutions elsewhere. This service, called Trials Search, differs from other clinical-trial information systems now in use. For example, the government-sponsored AIDS Clinical Trials Information Service provides a free telephone number (800/TRIALS-A) which anyone can call to ask questions about clinical trials in their area. However, the 800/TRIALS-A system is not set up to accept a patient's medical profile and automatically match the trials against it. Another computerized trials system, running at San Francisco General Hospital, keeps a database of potential volunteers and searches that database when one of its trials needs subjects. But in this system, volunteers sign up and do not know when (or if) they will be contacted; the Trials Search system, by contrast, operates at the potential volunteer's initiative, and provides a list of possible trials immediately. We do not know of any other service which does this. To use Trials Search, the patient fills out a one-page form, indicating past and present opportunistic infections (from a list of 20), past and present treatments (from a list of 18) and present laboratory-test values (nine are requested: T-helper count, white blood count, hematocrit, etc.; patients can obtain the values from their physician's office). This simplified medical history includes the most important information used in the inclusion and exclusion criteria for most clinical trials. Trials Search cannot, of course, tell for sure whether a patient will qualify for entry into a particular study; only the researchers running each trial can make that decision. But Trials Search can rule out the great majority of trials for which the person could not possibly qualify. (In the San Francisco area, about 80 clinical trials are currently running; Trials Search typically locates about ten to 15 of these, on the average, for each client.) The patient's medical form, which can be anonymous, is mailed or taken in person to Trials Search. It takes only about a minute for a trained operator to enter the patient's information, and the computer then prints a list of likely trials. There is a small fee for this service: no more than $7. per search, with reduced rates for persons with low income. This fee pays approximately a third of the cost of running Trials Search, which has also received small grants from the Bay Area Physicians for Human Rights, from AT&T, and from an anonymous individual. The project's organizers hope to acquire more substantial funding, after usage of the system proves that it is meeting a need. If medical centers in other areas want to install this system, it would be technically easy because the only equipment needed is a Macintosh computer with a laser printer. There is no telephone or network connection to any other system. Little computer expertise would be required. However, no decision has yet been made about whether to distribute the software; and documentation would need to be written to instruct personnel at other medical centers on how to install and operate the system. Trials Search is now open for persons with AIDS or HIV (in San Francisco or elsewhere) who want to find out about San Francisco area trials for which they may qualify. For more information, call Jay Seward, at the Institute for HIV Research and Treatment of Davies Medical Center, 415/565-6368, 10 a.m. to 4:30 p.m. weekdays except Wednesdays. ***** New DNCB Study Opens A pilot study of the potentially immune-enhancing substance dinitrochlorobenzene (DNCB) is being co-sponsored by Project Inform and Children's Hospital in San Francisco. DNCB was once in wide use by the HIV "treatment underground," but the lack of a standard dose and application at the time produced mixed results. Because DNCB was unpatentable, the mainstream AIDS research establishment seldom pursued it seriously as an HIV treatment. DNCB is in common use, however, as a diagnostic lab test applied topically to the skin, to assess delayed hypersensitivity in immune function; it has also been tried experimentally to treat alopecia, warts, and melanoma. Available as an industrial solvent, particularly in photographic development, DNCB has been reported to elicit an immunomodulatory activity from CD8 cells, and from Langerhans cells, which are considered a pivotal connection between the body's dermatological and immunological systems. When brushed onto a small area of the skin, DNCB gradually provokes a systemic immune reaction like that caused by poison oak or poison ivy, apparently inducing Langerhans cells to step up their capacity for signaling the proliferation of T- cells. This study of DNCB is innovative for its plans to observe any correlation between skin and blood markers; it is designed only to monitor people who have already chosen to use DNCB (with or without AZT). It will be supervised by an HIV- knowledgeable physician on staff at Children's Hospital, Rafael Stricker, M. D. The protocol for the study was written by Dr. Stricker and Joseph Brewer of Project Inform. For information about participating, interested persons can call 415/552-7464. ***** In Memoriam: Temple Minner, David Smyth Philadelphia AIDS activist Temple Minner died November 19. A vocal force in the local treatment and services scene, Temple helped to build the Philadelphia organization "We the People," and with Kiyoshi Kuromiya he co-founded the respected Critical Path AIDS Project newsletter. We spoke to Temple frequently on the phone and we will miss his help and his strong convictions. San Francisco writer David Smyth died October 24. David was fervently involved in treatment issues, and had contributed valuable research and writing in the past to AIDS TREATMENT NEWS. ***** San Francisco: CARE Bill Hearing, December 11 The San Francisco HIV Health Service Planning Council is holding a public hearing for community input on the needs and priorities for HIV services in San Francisco. The Council has been appointed by Mayor Agnos to set the priorities for allocating the Ryan White CARE bill disaster relief money. The legislation directs the money to be used for direct health care, both inpatient and outpatient, and for support services for people with HIV; the money cannot be spent on education or prevention. San Francisco will be receiving approximately $6.4 million with an additional $6.4 million available through competitive grants. The Council is required to come up with a plan for spending the money by February 1991, so they are working on a very short timeline. The public hearing is being held to listen to the needs and priorities that the people of San Francisco feel are the most urgent and important. The Council has asked that speakers present their top priorities and identify what type of services they would suggest to meet those needs. Individuals who cannot attend the hearing are encouraged to send in written comments and suggestions. The hearing will be December 11, 1990 from 3-6 pm, at the Department of Public Health, 101 Grove Street, room 300. Written comments should be sent as soon as possible to HHSP Council, c/c DPH AIDS Office, 25 Van Ness, 5th Floor, San Francisco, CA 94102. Comment The Council wants to hear from individuals about the most important needs and priorities for HIV services, and about existing service gaps. You can help by letting it know about any problem areas where you have first-hand knowledge or experience. One area that we believe especially needs more funding is benefits counseling -- helping persons with AIDS or HIV obtain public benefits or private insurance to which they are legally entitled. Unfortunately, institutions have an incentive to complicate their forms and procedures to keep from paying money due. There are cases of applications being stalled in the hope that persons with AIDS will die before benefits have to be paid. It can be difficult for persons who are ill to protect themselves, without assistance. Two organizations, AIDS Benefits Counselors and the San Francisco AIDS Foundation, provide different kinds of benefit assistance. The AIDS Foundation teaches people how to apply; AIDS Benefits Counselors provides one-on-one assistance with applications, and organizes volunteer attorneys when needed for appeals. Anyone with first-hand knowledge about problems in obtaining benefits should contact the Council at the address above. Which organizations have been most effective in providing assistance? Where could additional funding do most good? ***** ACT UP Affiliates, Buyers' Clubs, and PWA Coalitions, December 1990 For ACT UP affiliates not included below, call ACT UP Network in San Francisco, 415/861-7505. For PWA Coalitions, call NAPWA (National Association of People With AIDS) in Washington, D. C., 202/429-2856. This list only includes organizations with a publishable phone number. We will publish an international list later. If you know of any organization which should be listed here but was omitted, please call Denny or Laura at AIDS TREATMENT NEWS, 415/255-0836. The identification codes below are "A" for ACT UP or similar activist group, "B" for Buyers' club, and "C" for PWA Coalition. ALASKA Anchorage, Alaskans Living With HIV 907/272-6210 "C" ARIZONA Tucson, PACT Buyer's Club 602/322-9808 "B" Tucson, PWA Coalition 602/322-9808 "C" CALIFORNIA Long Beach, ACT UP 213/435-4346 "A" Los Angeles, ACT UP 213/669-7301 "A" Los Angeles Buyer's Club 213/748-1295 "B" Mendocino, ACT UP/Redwood Region 707/485-5867 "A" Oakland, ACT UP/East Bay 415/420-8864 "A" Orange County, ACT UP 714/744-6878 "A" Sacramento, ACT UP 916/552-1996 "A" San Diego, Being Alive 619/291-1400 "C" San Diego, Alliance 7 619/281-5360 "B" San Francisco, ACT UP/Golden Gate 415/252-9200 "A" San Francisco, ACT UP/San Francisco 415/563-0724 "A" San Francisco, Healing Alternatives 415/626-2316 "B" San Francisco, PWA Coalition 415/553-2560 "C" Santa Barbara, ACT UP 805/569-3299 "A" West Hollywood, Being Alive 213/667-3262 "C" COLORADO Denver, ACT UP 303/830-0730 "A" Denver, Health Action Project 303/894-8650 "B" Denver, PWA Coalition 303/837-8214 "C" CONNECTICUT New Haven, ACT UP 203/562-2622 "A" New Milford, PWA Coalition 203/624-0947 "C" DISTRICT OF COLUMBIA Carl Vogel Foundation 202/293-5153 "B" DC, ACT UP 202/728-7530 "A" Lifelink 202/546-3166 "C" Oppression Under Target (OUT!) 202/234-3614 "A" The Positive Woman 202/745-1078 "C" FLORIDA Broward County, PWA Coalition 305/784-0314 "C" Coconut Grove, Cure AIDS Now 305/856-8378 "C" Dade County, PWA Coalition 305/576-1111 "C" Ft. Lauderdale, PWA Health Alliance 305/763-7723 "B" Jacksonville, PWA Coalition 904/387-9350 "C" Miami, ACT UP 305/576-1111 "A" Miami, Body Positive Resource Center 305/576-1111 "C" Orlando, Action Now 407/351-6930 "A"&"B" Palm Beach, PWA Coalition 407/845-0800 "C" Sarasota, AIDS Manasota 813/954-6011 "B" Tallahassee, ACT UP 904/847-7445 "A" GEORGIA Atlanta, ACT UP 404/286-6247 "A" Atlanta, PWA Coalition 404/874-7926 "C" ILLINOIS Central Illinois, ACT UP 309/827-6841 "A" Chicago, ACT UP 312/509-6802 "A" INDIANA Indianapolis, PWA Coalition 317/637-2720 "C" KANSAS Kansas City, ACT UP 816/753-5930 "A" Wichita, ACT UP 316/269-1183 "A" LOUISIANA New Orleans, ACT UP 504/944-4546 or 522-5105 "A" New Orleans, PWA Coalition 504/945-4000 "C" Shreveport, ACT UP 800/OUTCRYS "A" MAINE Portland, ACT UP Maine 207/774-7224 "A" Portland, PWA Coalition 207/773-8500 "C" MARYLAND Baltimore, ACT UP 301/837-5203 "A" Baltimore, PWA Coalition 301/625-1677 "C" Hyattsville, PWA Coalition 301/464-6964 "C" MASSACHUSETTS Boston, ACT UP 617/492-2887 "A" Boston, PWA Coalition 617/859-8333 "C" Provincetown, ACT UP 508/487-2063 "A" Springfield, PWA Coalition 413/734-8844 "C" MICHIGAN Detroit, Friends PWA Alliance 313/836-2800 "C" Grand Rapids, PWA Coalition 616/235-1372 "C" MINNESOTA Minneapolis, ACT UP/MN 612/870-4214 "A" Minneapolis, The Aliveness Project 612/822-7946 "B"&"C" MISSISSIPPI Jackson, PWA Coalition 601/353-7611 "C" NEW HAMPSHIRE Newmarket, Positive Action 603/659-8442 "C" NEW JERSEY Bergenfield, PWA Coalition 201/944-6670 "C" Central Jersey, ACT UP 201/247-9404 "A" Newark, Community Project for PWAs201/824-5900X228"C" New Jersey Caucus, 201/757-3306 "A" NEW MEXICO Albuquerque, NMAPLA 505/266-0342 "C" NEW YORK Buffalo, Niagara Frontier AIDS Alliance 716/852-6778"C" Long Island, ACT UP 516/338-4662 "A" Long Island, PWA Coalition 516/756-2354 "C" New York City, ACT UP 212/564-AIDS "A" New York City, PWA Coalition 212/532-0568 "C" New York City, PWA Health Group 212/532-0280 "B" Syracuse, ACT UP 315/475-1544 "A" OHIO Columbus, ACT UP 614/444-8137 "A" OREGON Portland, ACT UP 503/284-0262 "A" PENNSYLVANIA Allentown, PWA Coalition 215/433-5444 "C" Philadelphia, ACT UP 215/222-8815 "A" Philadelphia, We The People 215/545-6868 "B"&"C" Pittsburg, Cry Out! 412/683-9741 "A" PUERTO RICO ACT UP 809/721-4353 after 5 p.m. "A" RHODE ISLAND Providence, ACT UP/Rhode Island 401/461-4191 "A" Providence, Lifeline PWA Coalition 401/421-5344 "C" TENNESSEE Nashville, People Living With AIDS 615/385-1510 "C" TEXAS Austin, ACT UP 512/477-AIDS "A" Austin, PWA Coalition 512/472-3784 "C" Dallas, Buyers' Club 214/826-7455 "B" Dallas, GUTS 214/621-6817 "A" Dallas, PWA Coaltion 214/941-0523 "C" Houston, ACT UP 713/433-9818 "A" Houston, PWA Coalition 713/522-5428 "C" UTAH Salt Lake City, PWA Coalition of Utah 801/359-9619 "C" WASHINGTON Seattle, ACT UP 206/726-1678 "A" Seattle Treatment & Education Project 206/329-4857 Statement of Purpose AIDS TREATMENT NEWS reports on experimental and complementary treatments, especially those available now. It collects information from medical journals, and from interviews with scientists, physicians, and other health practitioners, and persons with AIDS or HIV. 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. We also examine the ethical and public-policy issues around AIDS treatment research and treatment access. [Obsolete subscription information has been removed. See the latest issues for up-to-date information. -- sysop] &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& End of display