gilbert@tce.COM (Gilbert Cornilliet) (02/27/91)
Hi there! This is a selection of articles (mostly medical) from the February 1991 Being Alive Newsletter. I am one of the editors of this Newsletter. Comments, suggestions, critics, submission of articles, etc are welcome. My E-mail address is gilbert@tce.com. Please share this information with your friends. Take care. Gilbert. ======== TABLE OF CONTENTS ======== BEING ALIVE STATEMENT HOW TO SUBSCRIBE TO THE BEING ALIVE NEWSLETTER ABOUT THE BEING ALIVE NEWSLETTER PROJECT INFORM'S TOWN HALL MEETING HISTORY IN THE MAKING: MACS AT YEAR SEVEN PRACTICAL APPLICATIONS OF NUTRITION CLARITHROMYCIN: A BATTLE FOR TIME EARLY CARE FOR HIV DISEASE EPO APPROVED! HOW PROTEASE INHIBITORS WORK COMMON SKIN DISEASES IN HIV INFECTION ============================================================================== BEING ALIVE STATEMENT Being Alive is an organization OF and FOR people with HIV/AIDS. We understand the pain and the fear; how easy it is to hide, how difficult it can be to come to terms with this disease and reach out. Being Alive is the means we have created to help us connect with each other, bring others like us out of isolation, and take charge of our lives, our care and our destiny. Being Alive provides the following services to its members and the community: Advocacy HIV Fight Back! Library Medical Update Neighborhood Networks Newsletter Peer Counseling Roommate Referral Social Events Speakers Bureau Support Groups Vital Information TOGETHER, WE ARE MAKING A DIFFERENCE. ============================================================================== HOW TO SUBSCRIBE TO THE BEING ALIVE NEWSLETTER We are happy to provide the Being Alive Newsletter to people who cannot afford to purchase a subscription; however, we ask that anyone who can afford to subscribe, do so. |__| Enclosed is $12 for a six month subscription. |__| Enclosed is $20 for a one year subscription. |__| I cannot afford to pay for a subscription. Please enter my free subscription. |__| Here is an additional donation to support Being Alive. Name: Phone: Address: City: State: Zip: Please note that all names are kept confidential 4222 Santa Monica Blvd. Suite 105 - Los Angeles, California 90029 TOGETHER, WE ARE MAKING A DIFFERENCE. ============================================================================== ABOUT THE BEING ALIVE NEWSLETTER The Being Alive Newsletter is produced and published by Being Alive, People with HIV/AIDS Action Coalition, which is solely responsible for its content. If you have articles you would like to submit to the Being Alive Newsletter or if you just want to help, please contact the Being Alive office during regular hours. Please note: Information and resources included with your Newsletter are for informational purposes only and do not constitute any endorsement or recommendation of, or for, any medical treatment or product by Being Alive, People with HIV/AIDS Action Coalition. With regard to medical information, Being Alive recommends that any and all medical treatment you receive or engage in be discussed thoroughly and frankly with a competent, licensed, and fully AIDS-informed medical practitioner, preferably your personal physician. Being Alive and Being Alive Coping Skills Support Group are trademarks of Being Alive, People With HIV/AIDS Action Coalition, Los Angeles. Opinions expressed in various articles in the Being Alive Newsletter are not necessarily those of Being Alive's membership. Any individual's association with Being Alive or mention of an individual's name should not be, and is not, an indication of that person's health status. ============================================================================== PROJECT INFORM'S TOWN HALL MEETING reported by Jim Stoecker The evening of January 8 saw Martin Delaney once again in Los Angeles for the quarterly Project Inform Town Hall meeting. A large crowd was on hand at West Hollywood Park to hear Delaney, Executive Director of Project Inform, speak about a wide range of topics. FDA APPROVAL PROCESS Delaney began the evening by discussing the ongoing licensing fight with the FDA over DDI and DDC. Last summer, AIDS activists initiated an effort to have the FDA review the data on these drugs now rather than waiting for the completion of formal studies sometime in 1991. Support for this early review was heard from the National Cancer Institute, NIAID and many of the ACTG researchers. The FDA has responded by saying that the manufacturers have not submitted applications for licensure. Technically this is true. For the drug companies to take this step, however, they need some sign that these drugs will be evaluated in a different way from the traditional method. What this means, says Delaney, is that we need to have newer ways for looking at surrogate markers and control data. For AIDS drugs, it is becoming increasingly clear that the T-4 helper cell count is the surrogate marker to look at. Dr. Broder of the National Cancer Institute analyzed data on all patients who have been in NCI programs on AZT, DDI or DDC since 1985. What he found was that not one patient whose T-4 count remained above 50 died or developed lymphoma. Clearly, according to Delaney, the T-4 count is "a measure of what this disease is doing" and, for those in the later stages of the disease, "a profound predictor of survival." In addition to recognizing the value of surrogate markers, we need a new understanding of how to control a study. In the past, as was done with AZT, you give one group the drug and the other group a placebo and"you counted to see how fast they died." Obviously, this can never again be an acceptable approach for AIDS drug research. So, in the absence of a placebo-receiving control group, the FDA is asking that DDI/DDC be compared to AZT. And they have suggested that these drugs need to be better than AZT for approval. Delaney termed this latter requirement "almost an impossible hurdle to clear at this time." Community activists have succeeded in getting the FDA to call a special meeting of the Antiviral Committee early in February. At the meeting, not just the FDA and its advisors will speak, also included will be representatives from NCI, NIAID, ACTG researchers, community activists, and the National AIDS Commission. All these participants help ensure that there will be a lively debate about changing the rules. Delaney believes that out of this meeting "will come the signal to the companies that they will indeed have this data reviewed in a different fashion than would normally be the case." The February meeting also signals a change in who is involved in the drug approval process. Activists have long sought to open up the process. As Delaney stated, "what we are trying to get at here is that the licensing prerogative of the FDA bureaucracy." This call for a "collective process" has a good deal of support, according to Delaney, even within the FDA itself. In the end, Delaney believes that by mid-February at least one, and possibly both, of the manufacturers will submit their drug licensing application. Activists will push the FDA for a quick turnaround so that DDI/DDC can be made more widely available through prescriptions. Delaney concluded by noting that what is at stake in this effort is not just the future of DDI/DDC. It is the development and accessibility of all new anti-HIV drugs, unless the rules change, drug manufacturers may shy away form further research and development. "If they are going to be asked to jump through all of the old hoops again, they have to consider how much time and effort they want to put into this with the risk of failure being so high," says Delaney. With all the possibilities for new drug therapies that loom on the horizon, the approval process needs to be simplified and sped up. FDA approval is clearly the only way to get wide access to a drug in the United States. Project Inform fought to parallel track/expanded access programs. but these programs leave too many people out; they do not work in an equitable way. Delaney now believes that the "only real solution" to providing true equal access is when "a drug is available on a prescription basis." NEW DIRECTIONS FOR PROJECT INFORM During 1991, Project Inform intends to create a national, grass roots action network. According to Delaney, this will allow activists throughout the country to directly participate in Project Inform's political actions on FDA reform, treatment access and research. Project Inform is also going to be working in the coming year to expand its educational coverage to other communities. Delaney admitted that the Project's educational materials "best serve the well-educated, middle class reader." Now there will be an effort to reach other groups that are being affected by HIV. Project Inform will also look at the possibility of funding research projects. In the past, the organization has conducted its own research. Delaney deemed this new approach "a smarter use of the money to give people who are willing to act in innovative ways...the means to move their research forward." Project Inform is interested in proposals "from every corner of work in this field." Finally, Delaney said that in 1991 Project Inform plans to become "increasingly noisy about accountability in research." Each year, enormous sums of money are spent in the U.S. on HIV-related research. Too often, however, studies are "never finished, never published, never presented, never discussed." In the past, there has been no one to blow the whistle. Now, Project Inform intends to become an active and aggressive whistle blower and demand accountability for the money spent. COMPOUND Q UPDATE The first Project Inform study of Compound Q has now been published in the journal AIDS. It is already on the stands in Europe and should be available in the U.S. next month. A second Project Inform study is now at the half-way point. About 50% of this study group has actually shown an increase in T-4 cells. This has surprised researchers since all of the people were treated with Q for some time before the study began. A study by the San Francisco City Clinic that looks at the long term efficacy of Q is now being readied for publication. Overall, about 50 of the 70 people in this study showed either an improvement or a halt in decline. About 20 had no response to the drug. Phase I studies of Compound Q have only found efficacy of 24 or 36 mg doses and only when using a two-step infusion. Lower doses did not produce any consistent results. Researchers have also noted differences between the Chinese and the American versions of the drug. It appears that Chinese Q is, on a weight basis, more potent than American Q. The Chinese drug is also slightly more purified and thus more likely to cause an allergic reaction. Delaney reported that "in more than 500 doses in the Phase I study of the American drug, there has been only one anaphylactic reaction." Delaney summed up his experience so far by noting that "Q has never been the incredible success that everyone hoped it was going to be." The study data so far seen does not appear to offer any major breakthrough in the fight against HIV. COMBINATION ANTIVIRALS Delaney went on to speak about what he termed "the most promising thing on the short term horizon," combination antiviral therapies. This approach has been talked about for the last few years. Originally, the thinking was that you combined an antiviral with an immune modulator. So far, however, we have not seen an immune modulator that really works. Now, we are looking more closely at combining available antivirals. The goal of combining antivirals is to increase antiviral activity. The drugs together should have a synergistic effect that makes them more efficacious in combination than each drug would be on its own. Moreover, by combining antivirals, we hope to block or at least slow down the development of resistance, such as we are seeing with AZT alone. Finally, combining drugs allows for lower doses of a given drug and thus lessens the toxicities. For over two years now, there has been an ongoing study of a combination of AZT and DDC as antiviral therapy. About fifty people have been involved as study subjects at the University of Miami and at the University of California, San Diego. All in the study are symptomatic HIV and had T cell counts below 200 at the start of the study. The average T cell count of the group was, in fact, under 100.All had no prior AZT or DDC therapy. Delaney offered what he termed a "preliminary analysis" of the study data. Full research results may not be published for another six months. The study involved multiple dose regimens. Varying amounts of AZT and of DDC were taken together. Two of the dose regimens were seen as effective. One regimen combined 300 mg of AZT a day with 1.125 mg of DDC; the other regimen included 600 mg of AZT with 2.25 mg of DDC a day. For those on the two above regimens, there was an average peak T cell gain of 164 points at roughly 2-3 months into the study. Delaney pointed out that, though this may not sound like a lot, "for somebody who is under 100 T cells, it sounds like a hell of a lot." T cell counts did begin to decline at about six months into the study but "the group average T cell counts remained above the baseline 12 months out." Moreover, the rate of decline was much less steep than that found when studying the use of AZT alone. So far there has been no data on the development of resistance, though Delaney expects to hear about this soon. Another study is underway that combines AZT with DDI. This study uses a group with a profile similar to that of AZT/DDC study group. At six months into the study, Delaney reports "the only thing that the investigators are willing to say is that it looks about the same at this point as the AZT/DDC study did at six months." Both these studies seem to confirm that "combining drugs directly on a daily basis may be the most effective thing that we have." Researchers have also been looking at "alternating therapies." In this approach, one antiviral is taken for a month or a week and then any other antiviral is taken for a month or a week. Studies of alternating therapies have been ongoing for some two years, but Delaney termed their results "extremely modest." At best, there is a reduction in toxicity, but no real improvement in efficacy. Combined antivirals, on the other hand, appears to make things better and that is where we want to get to. But what is the point of all this, if the only antiviral generally available is AZT? As Delaney put it, "You can't get combination therapy unless you can get the drugs to combine." Thus, we move from the scientific question back to the political question. We need to have both DDI and DDC approved by the FDA and widely available by prescription. Then, physicians and patients can develop the combination therapy that works best for the individual. NEW DRUGS IN DEVELOPMENT Delaney spent a good part of the evening discussing new drugs that have come out of what he termed "the rational drug development process." This process looks at the molecular structure of HIV, studies how the virus operates, and then begin to speculate how best to interfere with it. Rational drug design "creates molecules that are much more specific to the activity of the virus." The goal is to develop drugs that are highly specified to fighting HIV and thus more efficacious and less toxic than what we currently have available. Protease inhibitors are one type of drug that we are currently hearing more and more about. Protease is an enzyme that the virus needs to reproduce and this enzyme comes into play at the last stage of the HIV life cycle. Before the virus can attach itself to another living cell, its envelope must be clipped and shaped to allow its integration into that other cell. Protease does this shaping. It functions, as Delaney put it, as "the hair dresser of the virus." Without this shaping, the virus "remains a non-functional lump." By inhibiting the protease from functioning, we might be able to render the virus sterile. What is also important is that the protease for HIV is unique; it is not like other protease enzymes in the body. Thus, a drug to inhibit just this one type of protease has potential to be both maximally effective and minimally toxic. A number of the large drug companies have been working for some two years now to create a molecule that would interfere with protease enzymes. Delaney reported that he has "talked to most of the companies working on this and these people are excited." The push now is not only to develop a molecule, but more importantly, to turn it into a drug. Hoffman-LaRoche, the manufacturer of DDC, has already begun some tests of a first generation protease inhibitors in Great Britain. U.S. tests are scheduled to begin soon at the University of Miami. Merck, Sharpe and Dunne, the company that first characterized the protease enzyme, found toxicity problems with their compound during animal testing. They appear to be at least six months away from human testing. Upjohn seems to be further along. Delaney reported that their protease inhibitor "seems to produce a lasting effect from a single dose." Thus, Upjohn foresees a monthly administering of the drug. Delaney cautioned, however, that "this is laboratory talk. We aren't sure what's going to happen when it's put into the human body." Both Abbot Laboratories and Smith, Kline and Beecham are also working on their own variants of protease inhibitors. Another set of drugs currently in development are termed advanced or second generation reverse transcriptase inhibitors. These drugs inhibit the same enzyme that AZT does, but do so in a much more specified way. Thus, the hope is that we will not have the toxicities with these new drugs that we have with the current generation of reverse transcriptase inhibitors. Some of the advanced RT inhibitors are already moving into human studies. Merck, Sharpe and Dunne have begun testing two drugs at the NIH in Washington. These are two closely related compounds and we should have preliminary reports of their value in the next few months. Hoffman-Larouche is also developing new compounds that are anti-reverse transcriptase. The company, however, has told Delaney that "how they're treated on DDC will in fact have a big impact on how hard they are going to work on these other drugs." Once again, we return to the importance of the political agenda around FDA reform. The last of these new drugs is called a TAT gene inhibitor. The TAT gene is one of the genes that controls the activities of HIV by regulating its reproductive cycle. Delaney reported that "there is some belief that if you could regulate this gene, you could change the nature of the virus into something far less destructive than it is." A number of companies are working on developing these compounds. Delaney concluded his remarks on drugs in development by cautioning against expectations of early availability. One must always remember that there exists "that huge gap between observations about a compound and the development and availability of the real drug." It would be a mistake to think that we are going to have protease inhibitors, second generation reverse transcriptase inhibitors, or TAT gene inhibitors within the next six months. In the short term, the "tenable expectation," says Delaney, is combination therapy with already existing antivirals. ============================================================================== End of Being Alive Newsletter (February 1991 - part 1/2)