Date: Sat, 11 Mar 1995 20:27:47 -0800 (PST) From: "John S. James" AIDS TREATMENT NEWS #218, March 3, 1995 phone 800/TREAT-1-2, or 415/255-0588 CONTENTS: IL-2: U.S. National Institutes of Health Study Published Immune Restoration: Conference Outlines Future Directions Proving Clinical Benefit in Small, Rapid Trials: Statement to National Task Force on AIDS Drug Development Sulfasalazine: Arthritis Drug Increases CD4 Count? Viatical Settlement Tax Reform: Republicans Support Relief, Democrats Divided Research Meetings, March 1995 ***** IL-2: U.S. National Institutes of Health Study Published by John S. James Results of the leading study of interleukin-2 (IL-2), an experimental immune-based treatment for HIV, were published in the NEW ENGLAND JOURNAL OF MEDICINE on March 3. While this research, conducted by H. Clifford Lane, M.D., and 12 other researchers at the U.S. National Institute of Allergy and Infectious Diseases, is an important contribution to developing a new kind of treatment for AIDS, and for other diseases as well, IL-2 is not a treatment that many patients will want to use now. IL-2 is a substance normally produced in the body which stimulates the growth and development of T-cells and other immune cells. It is also a prescription drug, approved for use in treating metastatic renal cancer. IL-2 treatment can cause serious toxicities, however, because the body's own IL- 2 is produced in small amounts and used locally; but when the same substance is injected, it raises the level throughout the bloodstream, which is not how the body's own IL-2 acts. At this time IL-2 has serious drawbacks as an AIDS treatment: * It did not work in persons with low CD4 (T-helper) counts; in those with a CD4 count under 200, it seldom showed any benefit, and it also caused more serious side effects than in those with higher counts. * Even in those with CD4 counts over 200, it did not substantially raise CD4 counts in four out of ten of the patients, for unknown reasons. * While IL-2 was being administered (usually for five days every two months), it often caused severe side effects, described as worse than a bad case of the flu. Some patients had to spend part of each five-day treatment in bed. * When IL-2 did work, it greatly raised the CD4 count, and with repeated treatments, the count remained high. But it is not known how well the CD4 cells are working; and there is no proof yet that the treatment provides overall clinical benefit to patients. * IL-2 also stimulates the growth of HIV. About half the people treated have a large but temporary jump in viral load right after each injection -- even though everyone receiving IL-2 was also taking an anti-HIV treatment, such as AZT or ddI, to minimize this. * The results so far are based on uncontrolled studies of only a small number of patients. * IL-2 is expensive. The main reason why it is unlikely that IL-2 will be widely used at this time is that, at least with the antivirals now available, it does not work for those with advanced AIDS. And those who are doing well enough to use the drug may not want an experimental treatment with considerable drawbacks and no proven clinical benefit yet. But there are also reasons why this research is important: * When IL-2 does raise CD4 counts, they often went up by several hundred or more, bringing them into the normal range, and keeping them there for a year or longer. * In the future, when better antivirals (such as protease inhibitors) are available, it is possible that IL-2 may work for patients with more advanced disease. This is because the drug may be failing in more advanced patients because it is stimulating the growth of HIV. So far this is only a theory; it is now being tested in a trial which combines IL-2 with the Merck protease inhibitor. * It may be possible to use IL-2 in lower doses, or with different dosing schedules, to reduce side effects. * The IL-2 studies are producing new knowledge about the immune system in HIV disease, knowledge which could lead to a new class of immune-based treatments. * If IL-2 is indeed improving immune response, that could be useful in many different diseases. For example, a NIAID trial of IL-2 for treating drug-resistant tuberculosis or other refractory mycobacterial infection (in persons without HIV) is now open and recruiting volunteers. The March 2 Report The information published March 2, which represents the state of IL-2 research as of about a year and a half ago, has basically been known to the AIDS community for some time. A few HIV physicians are already treating patients with IL-2, based on this work. The article reports on three groups of patients: (1) The first group -- 23 patients in a dose-escalating trial, all with CD4 counts greater than 200 -- received a single course of treatment, a continuous intravenous infusion lasting either five or 21 days. The doses ranged from 1.8 million IU (international units) to 24 million IU per day. The maximum tolerated dose was found to be 18 million IU per day, when the drug was given for five days. (2) The second group, of ten patients with CD4 count over 200, received a five-day course of intravenous treatment (initial dose 18 million IU per day) every eight weeks. Eight of the ten required dose reductions (to 12 million IU or 6 million IU per day) due to side effects, and two of these eight chose to discontinue the treatment, although they remained in the study for followup. At the time data was collected for publication, five of the ten had received IL-2 treatment for two years. The average CD4 count (for all ten of these ten patients) went from about 400 to almost one thousand during the first year of treatment; the maximum CD4 increase was over 2200. But four of the ten did not respond -- their count stayed about the same, or even continued to decline. CD8 counts generally remained stable. An analysis of the cells using 2-color flow cytometry showed that the proportion of CD8 cells positive for HLA-DR was reduced -- which is considered a potentially good sign. Four of the ten patients showed a consistent increase in viral load (HIV RNA) after each infusion; but then the viral load quickly returned to baseline. There was no corresponding increase in p24 antigen. Another four of the ten had a viral load which remained below the 10,000-copy cut-off value of the test which was used (the Chiron branched DNA); if they had an increase in viral load, it was too small to be detected by the test. Two of the ten patients developed pneumocystis; both had failed to respond to IL-2, and both had a very high viral load, 555,000 and 435,000 copies per ml. Their last CD4 counts before being diagnosed with pneumocystis were 400 and 31, respectively. There were no other opportunistic infections in these ten patients. (3) The third group was 15 patients with CD4 counts under 200. Their side effects were more severe, and all 12 who received two or more courses of treatment required dose reduction. One patient, who took trichosanthin (compound Q) several days after an IL-2 treatment without telling the researchers, died two days later "from hypotension and lactic acidosis." Two of the six patients who started with CD4 of 100-200 had increases of at least 50 percent. But none of the six who started with under 100 had CD4 increases, and two of these patients developed opportunistic infections and died, about two and seven months after their last IL-2 treatment. Immunological tests showed that even in those with CD4 count under 100, their cells may have responded to the drug, suggesting that it may have been the virus which was preventing the CD4 count from increasing. Additional IL-2 Studies Three other studies at NIH of IL-2 in patients with HIV are now recruiting volunteers. One will test IL-2 in combination with strategies to reduce the activity of tumor necrosis factor (TNF), in the hope that this could improve the results of IL-2 treatment by reducing the side effects and/or viral increase which IL-2 can cause. Another is for people with T- helper count over 500, and will test two doses, given subcutaneously instead of intravenously, and every four weeks instead of every eight weeks. The third study is examining different durations of infusion, and different intervals of IL-2 infusion. Other IL-2 trials include randomized studies in the U.S. and Australia, and also a trial which combines IL-2 with the Merck protease inhibitor. For information about volunteering for IL-2 clinical trials, call the AIDS Clinical Trials Information Service, 800/TRIALS-A. You can also find out about AIDS-related trials conducted by the National Institute of Allergy and Infectious Diseases by calling 800/AIDS-NIH. ***** Immune Restoration -- Conference Outlines Future Directions by John S. James The Immune Restoration Think Tank, sponsored by San Francisco-based Project Inform, brings together an invited group of leading researchers from around the world for a three-day informal meeting to plan future research directions on immune restoration in late-stage AIDS, and to develop new collaborative projects. The fourth such meeting took place in Oakland, California, on February 24-26. Participants in the latest meeting included William Paul, M.D., Director of the U.S. Office of AIDS Research; Robert Gallo, M.D., National Cancer Institute; Clifford Lane, M.D. [see IL-2 article above], and Steven Schnittman, M.D., National Institute of Allergy and Infectious Diseases; Thomas Merigan, M.D., Stanford University; Robert Schooley, M.D., University of Colorado; John Dwyer, M.D., Prince of Wales Hospital, Australia; John Mills, M.D., MacFarlane Barnet Center for Medical Research, Australia; Michael McCune, M.D., Systemics; David Katz, M.D., Lidak Pharmaceuticals; Arthur Amman, M.D., Ariel Project; and about two dozen other researchers. The major reason for this project is the uncertainty about whether the immune system could recover, without assistance, from advanced AIDS, even if the virus could be completely stopped. No one knows the answer at this time. In tests of the new protease inhibitors, which are very good at stopping HIV at least temporarily in many patients, there are some cases of large CD4 (T-helper) count increases even in patients who started with very low counts, well under 50; however, the average response is not this good. Also, we do not know how well the new cells will work; CD4 cells are not all the same, but there are millions of different clones, each able to recognize particular antigens (foreign proteins from bacteria, viruses, etc.). Some of these clones might be missing when the CD4 cells return following antiviral treatment; if so, immune-restoration therapy may be necessary. The February 24-26 Meeting The Immune Restoration Think Tank meetings are by invitation only and are closed to the press, so that scientists can discuss preliminary work without fear of partial or misleading coverage. After the meeting, a press conference and a physicians' presentation provided an overview of what was discussed. The major (but not only) focus of the February 24-26 Think Tank is immune restoration by transplantation of "progenitor" cells -- cells which can grow and differentiate to replace those which are missing. Some of this initial work will be with people who have an HIV-negative identical twin. But there is also research in transplanting cells from relatives or other donors, after tests for compatibility. It may also be possible to transplant animal cells which cannot be infected by HIV -- or, by various approaches to gene therapy, make some of the person's own cells immune or resistant to HIV infection, then give them back to the patient. As a backup, in case these approaches fail, it may also be possible to harvest cells from persons in early-stage HIV infection, and freeze them for use later when they are needed by the same person. The cells might also be grown outside the body (to produce more of them) before they are returned to the patient. In addition, there is renewed interest in transplantation of part of a thymus gland. This may be necessary to "educate" the new T-cells as they mature in the body. Thymic transplantation may be needed because the thymus gland normally deteriorates with age. Also, the thymus might be damaged by HIV, although this is not known for sure. What Is Being Done Now? * Cryopreservation. In Australia, a project for cryopreservation (freezing) of cells from persons with early HIV infection is already underway; over 60 patients have had cells preserved, seven have had cells returned. One patient is believed to have had immune competence restored. * Thymic transplantation. Dr. Dwyer, now in Australia, plans to begin a new thymic transplantation project within months. In an earlier project, in 1984 at Yale, he already transplanted portions of a thymus gland into 20 patients with HIV. The benefit was temporary -- probably because there was no drug then to control the virus, and also because the technology necessary to preserve the gland was not available. Today, with the benefit of what has been learned in the last 11 years, the treatment may work better. * Cells from relatives. Immune-cell transplantation from relatives has been used recently in a small number of patients, with encouraging results in some cases. * Twin studies. In one recent case, cell transplantation between identical twins produced very good immune restoration. There is considerable interest in revisiting twin studies. * Stem cells. Stem cells are special cells which can divide into many kinds of immune cells, repopulating the immune system. A protocol to harvest stem cells from persons with HIV was designed in the previous Immune Restoration Think Tank, and is now about to begin. * Cells from animals. Successful engraftment of immune cells between species has been done in animal tests. And human immune cells have been successfully transplanted into baboons. But transplanting immune cells from animals to humans has not yet been attempted. * Specific immunity. Another area of interest is immune therapies to enhance specific immunity to a particular infection. Certain opportunistic infections and tuberculosis may be targeted first; later, such approaches may be used to restore or improve immunity to HIV itself. * HIV-specific immunity. By learning what components of the immune system are working against HIV, "we might learn to manipulate these, and have a major ally." * Endocrine system. Another therapeutic approach looks at the endocrine system -- which has unfortunately been largely ignored in AIDS research so far. It is known that various endocrine abnormalities occur in AIDS -- abnormalities which often can be routinely corrected in medical practice. It is possible that correcting some of them could make a big difference in the course of HIV disease -- but due to lack of research, not much is known so far. * Growth hormone. It might be possible to use human growth hormone for correcting various endocrine disorders -- not only for treating wasting syndrome, which is now becoming an accepted use for this prescription drug. * Gene therapy. Gene therapy to make stem cells resistant to HIV infection (so that they will repopulate the immune system with HIV-resistant cells) are still in the laboratory research stage, not yet ready for testing in patients. The ultimate goal of this research is to deliver a new gene with a single injection -- using a harmless virus as a "vector" to infect cells inside the body and insert the gene into the DNA of those cells. This would avoid the trouble and expense of processing cells outside the body, and could produce an AIDS/HIV treatment suitable for use around the world. * Scientific collaboration. An underlying theme is the rapidly growing interest in doing basic biological research in the context of clinical investigation. This requires a close working relationship between laboratory researchers, and those who do clinical trials. For more information about the Immune Restoration Think Tank, call Project Inform, 800/822-7422. ***** Proving Clinical Benefit in Small, Rapid Trials: Statement to National Task Force on AIDS Drug Development by John S. James The February 23-24 meeting of the National Task Force on AIDS Drug Development focused on protease inhibitors; our report on that meeting was not finished in time for publication in this issue. Below is our oral and written testimony to the Task Force. We were surprised by the widespread agreement with our statement on clinical trial design, in view of the intense disputes in this area. But it did not take long for old, sterile disputes to flare again. The objective has been to develop professional consensus. Now we must move from that consensus to action. Oral Statement to National Task Force I am John S. James from AIDS TREATMENT NEWS. I brought a statement that was passed around this morning. Instead of reading it, I will explain the two main points. One concerns looking for a way through the sometimes- destructive conflict around the issues of "surrogate markers" vs. "clinical endpoints." Here is one approach to consider. Assume provisionally that the markers are working, and use the markers in many small, rapid trials to optimize combinations of some of the treatments that we have; see how low we can get the markers, and eventually see how long we can keep them down. Then -- unless most everything we believe about HIV is wrong -- we can test those treatments without having to wait for people to get sick in the control arm; instead, the [combination, optimized] treatments should be strong enough to get people who are now sick, well. There are a number of recurrent infections, such as thrush, where people are dependent on specific antibiotics or antifungals, and if we can get the viral load down two or three logs and keep it down for weeks or months, will these people no longer depend on their medications? If so, we have shown clinical benefit -- in a small trial (ten, twenty, fifty people), in weeks instead of years, without great expense. This seems like the way to go. Scolnick (Edward Scolnick, M.D., President, Merck Research Laboratories): We agree with you completely. And we at Merck plan to do studies like that as the drugs become increasingly available. We think it's a good idea. James: I don't find much disagreement from anybody. But the question is, how to go from agreement to it actually happening? My other point is to bring in other kinds of treatments besides those in high-profile development; I have a list of about 30 possible treatments [which should be investigated], often prescription drugs approved for other purposes. These are substances already widely in use in people; we know the safety, we know the dose, we know the pharmacokinetics; we don't know the interactions [with drugs commonly used in HIV disease], those will have to be checked. But there is some rationale for testing these substances in HIV treatment, and they are not now being developed. With rapid screening trials, we can bring some of these in, too; we can add to the effectiveness of treatment combinations. Written Statement to National Task Force I started AIDS TREATMENT NEWS in 1987 to report on experimental, "alternative," and mainstream treatments, and have published over 200 twice-monthly issues since. Eight years of AIDS treatment reporting has shown what has worked -- and, far more often, what has not -- and how treatment development could be made to work better. Today the conventional wisdom says that after the protease inhibitors, the HIV drug pipeline is largely empty -- that there are no good drugs to test. In fact there are dozens of potential treatments to test. But they have fallen through the cracks because there is no big money behind them, and therefore they do not have enough professional momentum to overcome the normal obstacles to the development of any drug. They never reach the first small, well-managed, credible human trials, through which they might prove themselves. I have kept a list of about 30 such drugs and other treatments for which this initial testing would be exceptionally easily, because these substances are already in widespread human use for other purposes, so the dose, safety, pharmacology, and manufacturing are already well known. All of them have a scientific rationale (sometimes unpublished) as to why they should be tested for HIV. Yet almost none are being developed in any serious way. (And this list of 30 does not include Chinese or other traditional or indigenous medicines, which could provide many additional substances and other treatment strategies to test.) Today the most notorious of these missed opportunities is hydroxyurea. I do not need to re-tell the story; most of you know it already. Consider another example. Two major epidemiological studies have found a substantial survival benefit associated with consumption of certain micronutrients. Up to a 50 percent reduction in relative risk of disease progression and of death has been associated with small doses (not megadoses) of vitamins B6, B1, B2, C, niacin, and others. Increased risk was found with almost any intake of zinc. If these associations are causal ones, which is plausible although not proven, then an immense contribution to patient care could be implemented at no risk and almost no expense. Another epidemiological study unexpectedly found a strong association between use of some but not all antidepressants, and substantially reduced disease progression and increased survival. Apparently no one has any idea of the mechanism of action. This work is not yet published. How should these and other such treatments be researched, when obviously there are not enough resources for a large clinical trial of every proposed treatment or combination? We propose two different research strategies for two different cases -- when you believe you know the mechanism of action and have a plausible marker to measure it, and when you do not. I. If you have a proposed mechanism and markers. This case would apply to an antiviral like hydroxyurea -- and also to combinations of approved and/or experimental antivirals, such as combinations of protease inhibitors, AZT plus 3TC plus a protease inhibitor, etc. First, use the markers (plasma HIV RNA and other assays in the case of antivirals) in small, rapid trials (for example, 10 to 20 patients each, lasting about six weeks plus additional followup) to compare and optimize different treatments, combinations, and strategies. The rapid "turnover" of information (possible because of rapid recruitment, conduct, and analysis of such trials) allows new trial designs to quickly benefit from the results of earlier trials. This creates an ideal environment for developing combinations (of both conventional and new treatments) which maximize impact on the markers. But since the markers have not yet been validated, how do we know that the combinations which best affect the markers actually benefit patients? One way would be to test the winning combinations against standard treatment in a conventional clinical-benefit trial. But there may a much faster, less objectionable, and less expensive way. All indications suggest that if a treatment can impact viral markers strongly enough, and for long enough (e.g. reducing viral load by more than 100 fold for a year or more), then it will show benefit not only by preventing disease progression and death (which requires many subjects and a long time to see), but also by getting certain sick people well (which can be observed much more quickly). Many patients, for example, have ongoing infections such as thrush or sinusitis, which require continuing suppressive treatment with antifungals or antibiotics. A truly effective antiviral or immune-based treatment might visibly improve such infections, even though it had no specific effect against the organism. (We have already seen hints of such effects in trials of existing treatments, such as thymopentin, which are probably far weaker than an optimized combination could be.) This strategy, of optimizing marker responses to produce combination treatments powerful enough to get people well, could then produce statistical proof of clinical benefit in a small, rapid, ethical, controlled trial comparing the optimized combination to standard treatment for the infection. We would no longer need to wait for death or disease progression. And if this strategy should fail, what is the worst-case scenario? The strategy could fail in two ways. First, it may not be possible to find any combination treatment which can greatly and lastingly lower viral load. Or this approach could fail because combinations which do lower the viral load do not show quick benefit in patients. In either case, we will have wasted little time and diverted few resources, and will have produced information of great value in planning future research. II. If you do not know the mechanism of action, or have no markers. The conventional approach to studying an accidental discovery when no mechanism is known is to wait until laboratory advances somehow discover the mechanism of action. The wait may be indefinite, however, since without a suspected mechanism, laboratory research may not even get under way. And if it does, funding may delay it for years. We would suggest a different strategy for cases such as the micronutrients, or the antidepressants -- treatments already in routine human use, which have a rationale for testing in HIV disease, though they may have no known mechanism of action in this context. Start with exploratory trials looking at viral load, immunological tests, hematological tests, blood chemistries, etc. -- any marker which is operationally feasible, because it well standardized, known to be reliable, readily available, not too expensive, etc. Empirically test many markers (possibly hundreds) by running the tests before starting the mystery treatment, and then at intervals after the treatment is started. The results of this initial trial would provide hints, derived from human data, as to what the mechanism might be -- as well as leads for further research. And this early trial might also identify markers which could be used in optimization trials, as in strategy #1, above. In other words, when evidence suggests that a treatment might be helpful but no mechanism is known, consider testing markers empirically during a small, rapid trial of the treatment, to provide realistic, human data as a basis for further thinking and research. Note that a treatment with no known mechanism may be exceptionally valuable, as it may open a window onto an entire new class of therapy. Nothing suggested above is very expensive, nor dangerous to volunteers. But these strategies have not yet been used in AIDS. I would like to work with the National Task Force to see that such approaches receive serious professional evaluation, and are implemented if justified. List of Potential Treatments to Test We did not distribute this list at the hearing, but we had it available in case anybody asked for it. These are substances already in human use, with a rationale for testing in HIV disease, which currently are not being tested at all, or are not being developed rapidly. Our current list: Acyclovir (for survival); certain antidepressants (perhaps some tricyclics, such as amitriptyline and/or others); aspirin; camptothecin; coenzyme Q10; curcumin; DHEA; DNCB; doxycycline (at least three rationales proposed); garlic; HCG; hydroxyurea; hypericin; isoprinosine; ketotifen; NAC; naltrexone; niacin; papaverine; peptide T; ribavirin; sulfasalazine; thalidomide; thymomodulin, etc.; tobramycin; topotecan; vitamin B1; vitamin B2; vitamin B6; vitamin C; warfarin. ***** Sulfasalazine: Arthritis Drug Increases CD4 Count? by Denny Smith A drug widely used to treat arthritis and other autoimmune disorders may significantly increase CD4 counts in people with HIV. The drug, sulfasalazine, also known by the trade name Azulfidine, is an anti-inflammatory agent originally approved to treat ulcerative colitis, but like many drugs its uses have expanded to include treatment of other illnesses. It has, in the process, been observed to have certain "immunoregulatory" properties. Sulfasalazine's effect on CD4 cells was discovered incidentally by researchers at Cabrini Medical Center in New York who were treating HIV-infected patients with Reiter's syndrome. Reiter's is a chronic problem for some people with HIV, and it can produce a spectrum of seemingly disconnected symptoms, including joint inflammation, diarrhea, urethritis and conjunctivitis. The patients at Cabrini had been given sulfasalazine as one of the standard treatments for inflamed synovia (the transparent fluid that lubricates the body's joints) and arthritic pain. Over time, the researchers happen to notice that CD4 counts in four patients rose substantially, by an average of 200, even though three of them were not using any anti-HIV medication that could be credited with the increase. Last April, the researchers published their observations in THE JOURNAL OF RHEUMATOLOGY (volume 21, number 4). We recently discussed the potential of sulfasalazine with one of them, Hae Ran Rhim, M.D., who has since moved to San Francisco, where she has a rheumatology practice. Elaborating on points made in the report, Dr. Rhim said that sulfasalazine had already been known to suppress certain inflammatory responses of the immune system, including the production of cytokines like tumor necrosis factor and interleukins 1 and 2. Tumor necrosis factor is strongly associated with HIV replication, as well as with wasting and perhaps the development of dementia. The role of interleukins is more equivocal, with some considered to inhibit HIV progression, and others seeming to enhance it. Sulfasalazine is also known to be a scavenger of superoxide radicals, which are thought to provoke HIV by affecting the Long Terminal Repeat (LTR) of the virus. The LTR is at least one of the mechanisms responsible for regulating viral activity, and so it has been proposed that, theoretically, antioxidants could inhibit the LTR. (For more information on LTR inhibitors, see AIDS TREATMENT NEWS issues #192 and #196.) An increase in CD4 cells does not prove that a drug has had an impact on HIV replication. But if sulfasalazine lowers oxidative stress, or pacifies certain overactive components of the immune response, it would be consistent with some current directions in HIV research. Aspirin, curcumin, cyclosporin, NAC, pentoxifylline, thalidomide and vitamin C are other examples of agents that have been studied for their anti-inflammatory or antioxidant effects on HIV infection. And though they almost certainly will not replace drugs that are known to work directly against HIV, such as reverse transcriptase inhibitors or protease inhibitors, research suggests certain anti-inflammatories and antioxidants could complement antiretroviral treatments. Dr. Rhim mentioned that there are some side effects associated with the drug, including a sulfa-like reaction in some patients, and bone marrow suppression with long-term use, and of course the immunosuppression of the cytokines, mentioned above, that are overproduced in HIV disease. The allergic reaction might be avoided by starting with low doses and building up to the dose that is considered therapeutic for Reiter's syndrome, 2 grams a day. Bone marrow toxicity was not seen in the Cabrini patients, even in the one patient who was also taking AZT. The patients treated at Cabrini were relatively unusual in that three of them were not on anti-HIV drugs despite low CD4 counts. Otherwise, presumably, the effect of sulfasalazine would have been diluted and less dramatic. Dr. Rhim said it has been difficult to design a larger, strictly controlled, clinical trial using sulfasalazine to treat individuals with low CD4 counts, since there are now four -- soon to be five -- antiretrovirals approved for that purpose. Nonetheless, the Cabrini researchers, headed by Dr. Eddys Disla, have designed a controlled trial of sulfasalazine. The trial will begin recruiting March 1; interested persons in the New York area should call 212/995-6996. Dr. Disla told us that their original observations must be considered preliminary: it is not certain if or how sulfasalazine has a beneficial effect on HIV progression. Both Drs. Rhim and Disla reiterated the widely-held feeling that CD4 counts are a poor marker for HIV activity. They are at best a very approximate, delayed effect of HIV progression and/or anti-HIV treatments. The same is probably true for other markers that were once sporadically monitored, like p24 antigen, beta 2 microglobulin and neopterin. However, there are now tests to bypass these markers and to identify the impact of treatments like sulfasalazine on viral load. The quantitative polymerase chain reaction (PCR) RNA test and the branched DNA test can each measure the level of HIV in the blood quickly and accurately. The use of these tests, called HIV RNA assays, could make it possible to observe the effect of sulfasalazine on anyone with low CD4 counts and measurable HIV levels, even if they are also on other HIV treatments, and especially if they cannot join a clinical trial of the drug. [For extensive discussions of these tests, see AIDS TREATMENT NEWS issues #204, #210 and #211.] The new sulfasalazine study at Cabrini will monitor HIV RNA levels. Anyone with anecdotal experience using sulfasalazine is encouraged to share it with Denny Smith or John James at 415/255-0588. ***** Viatical Settlement Tax Reform: Republicans Support Relief, Democrats Divided by Bob Roehr and John S. James One provision of the Republican Contract with America could benefit persons with AIDS -- tax relief on the money received from a life insurance policy before death, by a person with a short life expectancy due to illness. Under current law, death benefits paid by life-insurance companies are not taxable. Or if the policyholder borrows from family or friends and in turn assigns them as beneficiary of the policy, that too is not taxable. But if the policyholder gets the benefit of the policy before death by either an "accelerated benefit" provision of the policy itself, or a "viatical settlement" program, then that money is treated like regular income and is taxable. Reformers see that it is obviously wrong to take money from a person with a terminal illness, who is likely to need it for emergency medical and living expenses while they are alive, when the same money would be tax free if it went to their estate after death. Some jurisdictions, including the states of California, New York, and New York City, have already enacted laws to exempt from local taxation payouts under both accelerated benefits and viatication. A legislative priority of the National Association of People with AIDS (NAPWA) is to similarly reform the Federal law. To understand the current effort to reform Federal tax law you need to know the difference between "accelerated benefits" and "viatical settlement." Accelerated benefits -- a provision of a small but growing number of insurance policies -- allows for pre-payment of a portion of the death benefit in advance of death. Terms and conditions are set by the insurance policy and are generally quite restrictive, available only in the very last stages of illness. Many people with AIDS find their financial needs occur earlier, often soon after they take medical retirement, to pay private health insurance premiums, medical co-payments, and other expenditures necessary for their well-being. The concept of viatical settlements evolved to meet these earlier financial needs of people with AIDS. Their development has also stimulated increased availability of and more generous terms in accelerated benefits. A viatical settlement is the purchase of a life insurance policy by an independent company. The policyholder in return names the purchaser as irrevocable beneficiary of the policy being purchased. Because only one company issues a particular life insurance policy but many companies are willing to purchase it, viatication offers a much greater choice of financial options. Most policies can be sold through the viatication process. However, certain new individual policies not past their period of contestability, some group policies, and policies written by financially shaky insurance companies may not meet the criteria for purchase by a viatical settlement company. House Republicans have introduced an appropriate reform bill (HR 8, the Senior Citizens' Equity Act) as part of their Contract with America; it includes tax relief for both accelerated benefits and viatical settlements. Everyone agrees that accelerated benefits should not be taxed; the controversy is over whether to extend the same tax treatment to viatical settlements. The Republicans on the House Ways and Means Committee, which is considering the bill now, are generally supportive of not taxing viatical settlements. But Democrats are divided; at hearings on January 19, Barbara Kennelly (D-Connecticut) supported tax exemptions for accelerated benefits, but strongly attacked the same treatment for viatical settlements. She reiterated that position in a letter published in the February 8 edition of the WASHINGTON POST. Many of the country's largest insurance companies are based in her district; unequal tax treatment would allow insurance companies to sell accelerated benefits on terms that policy holders would not have chosen if they had the option of viatical settlement with equal tax treatment. (Since most policies do not offer accelerated benefits on any terms, the practical result would to continue the present system -- those needing early access to life- insurance money could get it tax free if they could borrow from rich relatives or friends, but would be taxed otherwise.) Letters and calls to Congress are needed now -- especially to Democrats on the House Committee on Ways and Means, and especially from voters in their districts, or at least from their states. Some of them already support tax reform for both viatical settlements and accelerated benefits, but their support may not be secure. Tell them that viatical settlements, as well as accelerated benefits, should not be taxed. Write or call to: Sam Gibbons (D-FL), Ben Cardin (D- MD), William Coyne (D-PA), Harold Ford (D-TN), Andrew Jacobs (D-IN), Gerald Kleczka (D-WI), Barbara Kennelly (D-CT), Sander Levin (D-MI), Robert Matsui (D-CA), Jim McDermott (D- WA), Richard Neal (D-MA), Lewis Payne (D-VA), Charles Rangel (D-NY), and Pete Stark (D-CA). You can write to them at: The Honorable __, House Committee on Ways and Means, 1102 Longworth House Office Building, Washington, DC 20515; you can call them through the Capital Switchboard, 202/224-3121. For more information about this issue, call Gary Rose, National Association of People with AIDS, 202/898-0414, or Tom McCormack, Affording Care, 202/479-2543. ***** Research Meetings, March 1995 * Mechanisms of HIV Disease: The 1995 UCLA/UCI AIDS Symposium, March 2-5, Hyatt Regency Suites, Palm Springs, California. Contact: Ms. Nita Driscoll, Cancer Research Institute, University of California, Irvine, 714/856-5886, or Ms. Jo Sherman, UCLA AIDS Institute, 310/794-7209. * Engineered Vaccines for Cancer & AIDS, March 3-5, Fairmont Hotel, San Francisco. Contact: Professional Conference Management, Inc., 619/565-9921. * Eighth Annual HIV/AIDS on the Front Line Conference, March 13-14, Costa Mesa, California. Contact: 714/834-8020. * First International Symposium on HIV and Cytokines, March 15-17, Reims, France. Contact: Thomas Fiorina, Mercure Communication International, (33-1) 44.01.23.00; fax (33-1) 47.63.52.78. * Stanford HIV/AIDS Forum: Advances, Policy, and Self- Management, March 18, Kresge Auditorium, Stanford University Law School. Contact: 415/723-9933. * Second Annual HIV Clinical Trials: Strategies for Trial Design and Management, March 30-31, The Washington Marriott Hotel, Washington, D.C. Contact: Cambridge Healthtech Institute, 617/487-7989; fax 617/487-7937; email chi@world.std.com. ***** 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: Richard Copeland Thom Fontaine Tadd Tobias Statement of Purpose: AIDS TREATMENT NEWS reports on experimental and standard treatments, especially those available now. 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