Path: bloom-beacon.mit.edu!hookup!news.kei.com!MathWorks.Com!europa.eng.gtefsd.com!howland.reston.ans.net!wupost!wubios.wustl.edu!not-for-mail From: Michelle Murrain Newsgroups: sci.med.aids,sci.med,soc.motss,bionet.molbio.hiv,sci.answers,soc.answers,news.answers Subject: Sci.med.AIDS FAQ part 2 of 4 Followup-To: sci.med.aids Date: 5 Sep 1994 23:51:44 -0500 Organization: Hampshire College Lines: 1980 Sender: sma@wubios.wustl.edu Approved: Yes: Jeff Rizzo ,jfh@netcom.com (Jack Hamilton) Distribution: world Message-ID: <17368@sci.med.aids> Reply-To: aids-request@CS.UCLA.EDU NNTP-Posting-Host: wubios.wustl.edu Xref: bloom-beacon.mit.edu sci.med.aids:6788 sci.med:53814 soc.motss:132728 bionet.molbio.hiv:497 sci.answers:1543 soc.answers:1651 news.answers:25200 ======================================================================= ======= Section 3. Confidentiality. Q3.1 How is blood tested in the United States? Q3.2 What if a blood-bank finds out you are HIV positive? ----------------------------------------------------------------------- ------- Question 3.1. How is blood tested in the United States? All blood products in the U.S. are screened by ELISA assays for several infectious agents, including: HIV 1/2, HTLV I/II, HBV, HCV, Syphillis, Hepatitis B core, and a liver enzyme ALT, indicative of hepatic infections. Some blood donations are also tested for CMV, a more common virus that has devestating effects in immunocompromised individuals, such as cancer patients and transplant recipients. In addition to these laboratories, all donors are screened through questionaires that meet or exceed FDA requirements. ----------------------------------------------------------------------- ------- Question 3.2. What if a blood-bank finds out you are HIV positive? The Red Cross and other blood banks routinely test blood donations for HIV antibodies. The Red Cross has specifically asked that people not use blood donation as a way of finding out if they are HIV+. If you think you might be infected, go get a blood test. Many cities offer free anonymous HIV testing. Contact your local public health service office for details. This is particularly important if you think you might have been infected within the last six months, since there's the risk that you are indeed infected, but do not yet have antibodies to HIV. Blood donation is a fine thing to do--but how will you feel if you donate, then a month later you find out through some other means that you're HIV+? We're supposed to be making a gift of life, not death. The following article discusses how blood banks use the information, if you have tested positive for HIV antibodies. In addition to your possible role in killing another person, donating blood to obtain a free HIV test also risks your anonymity. From: McCullough J. The nation's changing blood supply system. JAMA. 1993 May;269(17):2239-45. "The coded identity of potential or actual blood donors who are found to be unsuitable on the basis of medical history or laboratory testing is entered into a donor referral registry (DDR). Before each donated unit of blood is made available for use, the coded identity of the donor is checked against the DDR to ensure that the donor has not been found to be unsuitable during a previous donation. Although potentially infectious donors are so informed and asked not to give blood in the future, this DDR check is thought to improve the safety of the blood supply by serving as an additional way of identifying potentially infectious blood should these donors return. The American Red Cross operates a single DDR with information from all of its 47 reginal centers. However, other blood banks' DDRs act only locally since there is no requirement that different blood banks in the same or neighboring communities exchange this DDR information. The operation of these DDRs costs money, consumes experts' time, and has the potential for many abuses such as failure to obtain informed consent and breeches of confidentiality. The value of a DDR in improving the safety of the blood supply has not been established. An analysis of the value of thse DDRs should be conducted, and based on the results, DDRs should be either eliminated or refined into an appropriate system." See also: Grossman BJ. Springer KM. Blood donor deferral registries: highlights of a conference. Transfusion. 1992;32:868-72. ======================================================================= ======= Section 4. Treatment options. Q4.1 General treatment information. Q4.2 AIDS and Opportunistic Infections. Q4.3 Guide to Social Security Benefits. Q4.4 What if you can't afford AZT? Q4.5 What about DNCB? (please contribute) ----------------------------------------------------------------------- ------- Question 4.1. General treatment information. [This article was published in AIDSFILE, 1993 Sept, Vol. 7, No. 3, p. 1-3. (Copyright 1993 The Regents of the University of California). The Regents grant permission for material in AIDSFILE to be reprinted for use by nonprofit educational institutions for scholarly or instructional purposes only, provided that (1) the author and AIDSFILE are identified; (2) proper notice of the copyright appears on each copy; (3) copies are distributed at or below cost.] Review of Clinical Guidelines - Antiretroviral Therapy Paul A. Volberding, MD Introduction A number of new observations have been made recently concerning antiretroviral therapy for HIV infection. Although new data is always welcome, lately it seems to cause as much confusion as clarification. Caregivers for patients with HIV disease continue to recognize the established benefits of antiretroviral therapy, but new uncertainties have been introduced. These uncertainties mean that we must consider the new information in order to make the best use of available treatments at the same time that we appreciate their limitations. Those who care for patients with HIV disease also anticipate the introduction of new classes of drugs, and we are beginning to determine how we might use these additional agents in our patient care. Review of Clinical Guidelines Antiretroviral therapy clearly has shown activity in delaying the progression and death of patients with HIV infection, especially when therapy has been tested in patients with more advanced disease. But even in asymptomatic HIV infection there is a general agreement of at least a transient clinical benefit from the use of nucleoside analog therapy. It is clear also that antiretroviral therapy improves various laboratory markers of the disease, including immunologic and virologic disease markers, such as CD4 cell counts and HIV p24 antigen levels. Further evidence of the clinical activity of these drugs comes from trials showing a second period of benefit when therapy is changed to a non-cross-resistant agent, for example, switching from zidovudine to ddI. In addition, we are encouraged by symptomatic improvement in patients with advanced disease who are started on antiretroviral drugs. Also, many retrospective epidemiology studies continue to show a survival advantage in patients taking these drugs. Despite continuing agreement on some of the benefits of antiretroviral therapy, we also face growing uncertainties. Recent studies have shown no survival advantage when antiretroviral drugs are used in asymptomatic HIV infection, and any benefit in slowing clinical progression seems to disappear when zidovudine monotherapy, at least, is given for a prolonged period. Questions continue as well about the degree of benefit of antiretroviral therapy for patients with advanced HIV disease. Early clinical trials of zidovudine, for example, were done before the routine used of PCP prophylaxis, which, by itself, delays progression to that common indicator of AIDS. Questions about the current status of antiretroviral therapy include: Which drug or combination is superior as initial therapy? When should this initial therapy begin? What is the duration of the benefit from initial therapy? How long should it be continued before other drugs or combinations are initiated? Finally it is important to consider: Which drugs should be used following initial therapy? What might we anticipate in the future from drugs in current clinical development? Beginning Therapy -- What and When Probably the easiest question at the moment in the field of HIV therapy is which drug to use to begin treatment. Data from ACTG 116A make it clear that zidovudine is superior to ddI as a monotherapy in previously untreated patients, and data from other studies show the superiority of zidovudine over ddC. An independent "State of the Art Panel" recently convened by the National Institute of Allergy and Infectious Diseases (NIAID) and chaired by Merle Sande, MD, UCSF chief of the medical service at San Francisco General Hospital, found an easy consensus that zidovudine monotherapy is the initial therapy of choice. Even here, however, other opinions may be heard, especially concerning the potential for initial use of combinations of nucleoside analogs. For example, the recent ACTG 155 trial in much more advanced disease tended to show a superiority of the combination of zidovudine and ddC, which was limited to patients with the highest CD4 cells (between 150 and 300). A large study, ACTG 175, is comparing initial combination with monotherapy, but the results from this trial are not anticipated before the end of 1995. In the meantime, combinations including zidovudine with ddI or zidovudine with ddC as initial therapy remain of interest. When best to initiate antiretroviral therapy is probably the most controversial question in the field of HIV management. Extended data from ACTG 019 demonstrate durable clinical progression benefit with the use of 500 mg of zidovudine daily in patients with asymptomatic HIV infection and with CD4 cell counts between 300 and 500, but these data are in apparent conflict with those from the recently completed Concorde Study. Concorde, enrolling more than 1700 patients with any level of CD4 count, compared the initial use of one gram of zidovudine daily with the same therapy deferred until after the person developed AIDS or ARC. After a median treatment duration of three years, and despite a clear and sustained CD4 improvement with the immediate use of zidovudine, there was no apparent benefit in the immediate treatment group either in clinical progression or survival. When the investigators analyzed a subset of the overall group with CD4 counts below 500 cells and after one year of therapy, a benefit similar to that seen in ACTG 019 was observed. Although Concorde was a powerful study, given the size and duration of follow-up, concerns have been raised that the dosage at one gram was excessively high and that the large number of patients allowed to begin therapy before they became symptomatic complicates the analysis. Also adding to the confusion are the recently published results of the European-Australian cooperative Group trial, which tended to find a clinical benefit with the use of zidovudine in patients with CD4 counts up to 750 cells. The State of the Art Panel recommended two broad options after considering the available data--initiating therapy in asymptomatic individuals with CD4 counts under 500 cells, or delaying this therapy until symptomatic HIV disease intervened. Another option favored by many clinicians is to follow patients, delaying therapy until evidence of more rapid disease progression becomes apparent as manifested by rapid declines in CD4 count or by a rise in p24 antigen or, especially, a rise in beta-2 microglobulin. At any rate, the clinician must discuss the various options with each patient, individualizing this decision according to the clinical and laboratory status of the patient and according to the patient's own desires. Duration of Therapy A second difficult question in the field of HIV management is how long to continue initial zidovudine. Again, the ACTG 019 experience would suggest that zidovudine monotherapy has a prolonged period of benefit, especially in patients with higher CD4 cell counts (300-500) when therapy is begun. On the other hand, ACTG 116A seemed to indicate that the initial superiority of zidovudine was lost after as little as two to four months of treatment with this drug prior to treatment with didanosine. Here again, the State of the Art panel could find little room for consensus. When therapy is begun in individuals with CD4 counts above 300, the panel suggested that it should be continued until the CD4 cell count fell below 300. When zidovudine monotherapy is begun in patients with CD4 counts under 300, the additional option of switching to ddI monotherapy after a fixed interval was raised, but again this interval was not defined. Once zidovudine monotherapy has been used, and when it is no longer felt to be effective for an individual, secondary therapy must be initiated. The choice of this therapy, however, is also uncertain. In moderate disease, with CD4 cell counts below 300, switching to ddI was superior to continuing with zidovudine in ACTG trials 116a and 116b/117, while switching to ddC was not of benefit in ACTG 155. On the other hand, from data gathered in CPCRA Trial 002, in patients with more advanced disease, ddI and ddC were equivalent in secondary treatment of patients previously treated with zidovudine who had progressed despite taking that drug or who were intolerant of zidovudine toxicity. In fact, ddC had a slight but significant superiority compared to ddI in terms of survival in this trial. It was hoped that combination therapy following zidovudine would be beneficial but questions have been raised following the results of ACTG 155. In this study, patients previously treated with zidovudine with CD4 cells below 300 were randomized to stay on zidovudine, start ddC monotherapy, or begin zidovudine and ddC combination therapy. Overall, there was no difference in clinical progression or survival among the three study arms. When the baseline CD4 counts are examined, however, it was found that combination therapy was superior in patients with higher CD4 cell counts, especially between 150 and 300. Therefore, it might seem advisable not to delay the introduction of combination therapy until patients have very advanced disease but rather to use such therapy earlier in the disease course. Whether zidovudine and ddI would be as good as zidovudine and ddC has not been investigated. Newer Classes of Drugs Along with new data on existing therapies, more information is available now on newer classes of drugs. These include nucleoside analogs, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and the tat inhibitor. Nucleoside Analogs. New nucleoside analogs in clinical investigation include d4T (stavudine) and 3TC. d4T has been much more extensively studied and appears effective in raising CD4 count and lowering HIV p24 antigen in a number of Phase 1 trials. It appears safe. Although cases of pancreatitis have been reported, they seem to be extremely rare. Neuropathy is the main toxicity but, again, it appears to be somewhat less than with ddI or ddC. d4T may not be suitable for combination with zidovudine as the two drugs have a negative interaction limiting their activation within the cell. On the other hand, d4T is a well-tolerated drug and may prove to be an alternative to one or more of the existing nucleosides. 3TC also appear safe and may be able to help restore sensitivity to zidovudine when the patient's HIV has become resistant. Reverse Transcriptase Inhibitors. The non-nucleoside reverse transcriptase inhibitors, including nevirapine and the Merck "L" drug, were recently thought to have limited value because they induce high-level drug resistance so rapidly. At the Berlin conference, however, one report showed that by increasing the dosage of nevirapine to 400 mg daily, a dose well above the level of resistance, prolonged benefit might be achieved. Also, it was shown that combining zidovudine with nevirapine delays the onset of nevirapine resistance. Thus, these drugs may still find a place in clinical medicine. At the same time, convergent therapy, using three drugs together, was disappointing because of simultaneous resistance to zidovudine, ddI and non-nucleoside reverse transcriptase inhibitors. Protease Inhibitors. Protease inhibitors seem to be gaining some ground. In Phase 1 trials, several of these compounds have evident antiretroviral activity, which was reflected in decreasing HIV p24 and increasing CD4 cell counts. Clinical benefits have not been established nor has the activity of these drugs used in combination with zidovudine been described. Because several structurally different protease inhibitors are being developed by different drug companies, it is hoped that at least one of these compounds will become more widely available soon for clinical use. Tat. While the protease inhibitors appear encouraging, tat inhibitors appear to be clinically inactive. In Phase 1 trials of the Hoffman LaRoche tat inhibitor, little or no antiretroviral activity was seen and it is probably that this class of drugs will not be developed further. Summary Given this complex and seemingly confusing information, what recommendations can be given to the clinician? Most important is to individualize the decision-making and to consider the desires of the patient even more than previously. Some patients gravitate easily to more aggressive therapy, while others prefer a more conservative therapeutic approach. With the former, initiating therapy at or even above 500 CD4 counts, perhaps even with a combination of zidovudine and ddI, may be considered. For more conservative patients, however, following the recommendations of the Concorde study may in order. In other words, defer the initiation of zidovudine monotherapy until the onset of clinical symptoms. Once the choice of initial therapy has been made, all other recommendations must also be individualized. No firm data are available to guide the decision about how long to continue a therapy or even about what to use next. Most of these options have not been compared directly in clinical trials. It would seem advisable to continue therapy longer in patients with relatively earlier disease when therapy is initiated. On the other hand, if patients have more advanced disease, for example, are symptomatic or have CD4 cell counts below 300 when therapy is begun, then a more rapid alteration of therapy to a non-cross-resistant drug or combination should be considered. The goal in each patient is to continue effective antiretroviral therapy for as long as possible, discontinuing the therapy if further benefits appear impossible. Although the results of recent clinical trials are disappointing in some respects, it nevertheless is important to have these data. Only then can we adjust our expectations and our patients' expectations of antiretroviral treatment and learn how to make the best use of the drugs that we have available. Recognizing the increasing need for the development of new classes of more effective drugs in combinations, we must still seek to maintain the optimism that enables progress in our patients' care. Dr. Volberding is a UC San Francisco professor of medicine and Director, UCSF AIDS Program at San Francisco General Hospital. References: ZDV and The AIDS Clinical Trials Group (1989-93): Aweeka FT. Gambertoglio JG. et al. Pharmacokinetics of concomitantly administered foscarnet and zidovudine for treatment of human immunodeficiency virus infection (AIDS Clinical Trials Group protocol 053). Antimicrobial Agents & Chemotherapy. 36(8):1773-8, 1992 Aug. Fischl MA. Richman DD. et al. The safety and efficacy of zidovudine (AZT) in the treatment of subjects with mildly symptomatic human immunodeficiency virus type 1 (HIV) infection. A double-blind, placebo-controlled trial. The AIDS Clinical Trials Group [see comments]. Annals of Internal Medicine. 112(10):727-37, 1990 May 15. [Editor's Note: This article reports the results of ACTG 106.] Fischl MA. Parker CB. et al. A randomized controlled trial of a reduced daily dose of zidovudine in patients with the acquired immunodeficiency syndrome. The AIDS Clinical Trials Group. New England Journal of Medicine. 323(15): 1009-14, 1990 Oct 11. Gelber RD. Lenderking WR. et al. Quality-of-life evaluation in a clinical trial of zidovudine therapy in patients with mildly symptomatic HIV infection. The AIDS Clinical Trials Group. Annals of Internal Medicine. 116(12 Pt 1):961-6, 1992 Jun 15. Hochster H. Dieterich D. et al. Toxicity of combined ganciclovir and zidovudine for cytomegalovirus disease associated with AIDS. An AIDS Clinical Trials Group Study. Annals of Internal Medicine. 113(2):111-7, 1990 Jul 15. Kahn JO. Lagakos SW. et al. A controlled trial comparing continued zidovudine with didanosine in human immunodeficiency virus infection. The NIAID AIDS Clinical Trials Group [see comments]. New England Journal of Medicine. 327(9):581-7, 1992 Aug 27. Koch MA. Volberding PA. et al. Toxic effects of zidovudine in asymptomatic human immunodeficiency virus-infected individuals with CD4+ cell counts of 0.50 x 10(9)/L or less. Detailed and updated results from protocol 019 of the AIDS Clinical Trials Group. Archives of Internal Medicine. 152(11):2286-92, 1992 Nov. Krogstad DJ. Eveland MR. et al. Drug level monitoring in a double-blind multicenter trial: false-positive zidovudine measurements in AIDS clinical trials group protocol 019. Antimicrobial Agents & Chemotherapy. 35(6): 1160-4, 1991 Jun. Meng TC. Fischl MA. Richman DD. AIDS Clinical Trials Group: phase I/II study of combination 2',3'-dideoxycytidine and zidovudine in patients with acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex. American Journal of Medicine. 88(5B):27S-30S, 1990 May 21. Sidtis JJ. Gatsonis C. et al. Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group. Annals of Neurology. 33(4):343-9, 1993 Apr. Sperling RS. Stratton P. Treatment options for human immunodeficiency virus-infected pregnant women. Obstetric- Gynecologic Working Group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Obstetrics & Gynecology. 79(3):443-8, 1992 Mar. Volberding PA. Lagakos SW. et al. Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases [see comments]. New England Journal of Medicine. 322(14):941-9, 1990 Apr 5. [Editor's Note: This article reports the results of ACTG 109.] See also: Aboulker JP. Swart AM. Preliminary analysis of the Concorde trial. Concorde Coordinating Committee [letter]. Lancet. 1993 Apr 3;341(8849):889-90. Comment in: Lancet 1993 Apr 17;341(8851): 1022-3; Lancet 1993 Apr 17;341(8851):1023; Lancet 1993 May 15; 341(8855):1276; Lancet 1993 May 15;341 (8855):1276-7; and Lancet 1993 May 15;341(8855):1277. Cooper DA. Gatell M. et al. Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. New England Journal of Medicine. 329(5): 297-303, 1993 Jul 29. Hamilton JD. Hartigan PM. et al. A controlled trial of early versus late treatment with zidovudine in symptomatic human immunodeficiency virus infection. Results of the Veterans Affairs Cooperative Study. New England Journal of Medicine. 326(7):437- 43, 1992 Feb 13. ----------------------------------------------------------------------- ------- Question 4.2. AIDS and Opportunistic Infections. AIDS and Opportunistic Infections NIAID BACKGROUNDER: Office of Communications, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 - September 1993 Opportunistic infections (OIs) cause most of the illnesses and deaths among people infected with HIV, the virus that causes AIDS. The National Institute of Allergy and Infectious Diseases (NIAID) leads the way in U.S. research on these life-threatening infections. As part of the NIAID effort, investigators are defining the optimal therapies, alone and in combination, to prevent and treat OIs. They seek ways to identify infections earlier and recognize resistance to therapies more quickly. What are OIs? The immune systems of most people with HIV gradually deteriorate, leaving them vulnerable to numerous viruses, fungi, bacteria and protozoa that are held in check in people with healthy immune systems. These microbes can become active in HIV-infected individuals, causing frequent and severe disease. NIAID uses a two-pronged approach to the prevention and treatment of OIs: basic laboratory research to learn how these microbes cause disease and clinical research to develop and evaluate promising therapies. Prevention and treatment of one such disease, Pneumocystis carinii pneumonia or PCP, has been a major thrust of the NIAID program. Other NIAID investigations include cytomegalovirus (CMV) infection, Mycobacterium avium complex (MAC) and tuberculosis (TB). Institute research focuses on these infections because, although they occur repeatedly among HIV-infected people, they are rare in the general population and few drugs are available now to prevent and treat them. PCP: The Most Common OI PCP remains the most common, life-threatening opportunistic infection in people with HIV, occurring in up to 80 percent of individuals who do not take preventive therapy. The PCP organism, a microscopic parasite, appears to infect most people during childhood. In people with healthy immune systems, the parasite normally remains dormant, but it may cause disease in those with damaged immune systems. PCP infection is characterized by a dry cough and shortness of breath. Individuals may experience other, less specific symptoms such as fever, fatigue and weight loss for weeks or even months before respiratory problems appear. As PCP infection progresses, the functioning lung tissue becomes clogged, which decreases the transport of oxygen from the inhaled air into the blood. At this point, the oxygen in the blood may be lowered to dangerous or even fatal levels. Without treatment, close to 100 percent of HIV-infected patients with PCP die. During the 1980s, the development of effective therapies led to better management of PCP. Drugs for preventing and treating PCP include aerosolized pentamidine and oral trimethoprim-sulfamethoxazole (TMP/SMX), but both can result in serious side effects that prevent some patients from taking the drugs. TMP/SMX is recommended more often than aerosolized pentamidine for treating and preventing PCP because the combination is effective, tolerated by about half of the patients who take it and may work against other disease-causing organisms as well. In 1992, an NIAID-supported trial proved that TMP/SMX is better than aerosolized pentamidine at preventing a second episode of PCP in people with AIDS who can tolerate either therapy. Although definitive research data are lacking, other agents may be considered in situations in which neither TMP/SMX nor aerosolized pentamidine can be given. The drug atovaquone is approved for patients with mild to moderate PCP who cannot tolerate TMP/SMX. One NIAID study showed that primaquine, an antimalaria drug, with clindamycin is an effective oral therapy for PCP. TMP with dapsone is an alternative treatment. The search for new, more effective, less toxic drugs and combinations of drugs to fight PCP continues. NIAID studies play an important role in this effort. One trial compares three drug regimens--TMP/dapsone, primaquine/clindamycin and TMP/SMX--for oral treatment of mild to moderate PCP. Another protocol looks at an 8-aminoquinoline, an antimalaria drug, while a third trial considers two regimens of TMP/SMX to prevent PCP. CMV: A Herpesvirus Infection with CMV, a virus in the herpes family, may occur throughout life. By age 50, about half of the general population has been exposed to this virus, yet most people do not become ill. After the original infection, the virus may lie dormant and reactivate itself if the immune system becomes suppressed. For people with HIV infection, CMV is one of the most frequent and serious OIs they face. CMV retinitis, an inflammation of the light-sensitive inner layer of the eye, is the most common CMV infection and leads to blindness if left untreated. Infections also may occur in the gastrointestinal tract, lungs, brain, heart and other organs. Both intravenous ganciclovir and foscarnet are approved to treat CMV retinitis. Lifelong maintenance on either treatment is required because the drugs do not kill CMV, they merely slow down its ability to grow. Even with therapy, the rate of relapse is high. NIAID studies of CMV and other herpesviruses have shown that intravenous foscarnet and ganciclovir are equally effective for CMV retinitis, although foscarnet was associated with increased survival for patients in the study. An ongoing trial is testing an oral form of ganciclovir to prevent CMV disease. The oral form of the drug would be much easier and safer for patients to take. MAC: A Bacterial OI Infection with MAC is diagnosed in up to 40 percent of people with AIDS in the United States, making it the most common bacterial OI. Usually, it affects people in advanced stages of HIV disease when the immune system is severely suppressed. The MAC organism is found widely in the environment and is thought to be acquired most commonly through the mouth or gastrointestinal tract. It can spread to the lungs, liver, spleen, lymph nodes, bone marrow, intestines and blood. MAC causes chronic debilitating symptoms--fever, night sweats, weight loss, fatigue, chronic diarrhea, abdominal pain, liver dysfunction and severe anemia. Rifabutin is the first drug to be approved for preventing MAC disease in people with advanced HIV infection. The Food and Drug administration based this approval on clinical studies showing that patients who received rifabutin were one-third to one-half as likely to develop MAC as were patients who received placebo. To prevent MAC disease, a U.S. Public Health Service Task Force on Prophylaxis and Therapy for MAC suggests that patients with HIV infection and fewer than 100 CD4 + T cells receive oral rifabutin for the rest of their lives unless disease develops. In the latter case, multiple drug treatment is needed. CD4+ T cells are immune system cells targeted and killed by HIV. No other drug regimen is recommended currently to prevent MAC. Azithromycin and clarithromycin are promising agents for prophylaxis, but studies of these agents have not been completed. Increasing evidence suggests that treatment can benefit patients with disseminated MAC, especially multiple-drug regimens including either clarithromycin or azithromycin. Therefore, the PHS task force suggests that all regimens, outside of a clinical trial, should consist of at least two drugs, including clarithromycin or azithromycin plus one other agent such as clofazimine, rifabutin, rifampin, ciprofloxacin and, in certain situations, amikacin. They recommend continued therapy for the patient's lifetime, as long as clinical benefit and reduction of mycobacteria are observed. NIAID has several studies under way looking at the roles of clarithromycin and azithromycin, and other drugs such as sparfloxacin, alone and in combination, to prevent and treat this serious disease. TB: An Airborne Disease TB, a chronic bacterial infection, causes more deaths worldwide than any other infectious disease. About one-third of the world's population harbors the predominant TB organism, Mycobacterium tuberculosis, and is at risk for developing the disease. The World Health Organization (WHO) estimates that 4.4 million people worldwide are coinfected with TB and HIV. WHO predicts that by the year 2000, TB will take one million lives annually among the HIV-infected. Because of their weakened immune systems, people with HIV are vulnerable to reactivation of latent TB infections, as well as to new TB infections. Transmission of this disease occurs most commonly in crowded environments such as hospitals, prisons and shelters--where HIV-infected individuals make up a growing proportion of the population. Active TB may occur early in the course of HIV infection, often months or years before other OIs. TB most often affects the lungs, but it also can cause disease in other parts of the body, particularly in people with advanced HIV disease. Of particular concern for people with AIDS is multi-drug-resistant TB (MDR-TB). MDR-TB can occur when patients fail to take their TB medicine for the prolonged periods necessary to destroy all TB organisms, which then become resistant to the drugs. These resistant organisms can be spread to other people. Even with treatment, for individuals coinfected with HIV and MDR-TB, the death rate may be as high as 80 percent, as opposed to 40 to 60 percent for people with MDR-TB alone. The time from diagnosis to death may be only months for some patients with HIV and MDR-TB, as they are sometimes left without adequate treatment options. The initial site of TB infection is in the balloon-like sacs at the ends of the small air passages in the lungs. In these sacs, white blood cells called macrophages ingest the inhaled TB organism. Some of the organisms are killed immediately, while others remain and multiply within the macrophages. If the organism breaks out of the sacs, TB can become active disease. This spreading sometimes results in life-threatening meningitis and other problems. NIAID launched the first large U.S. study to assess TB treatment strategies for people coinfected with HIV and TB. The study is aimed at finding state-of-the-art treatment. NIAID is the lead institute for TB research at the National Institutes of Health, supporting more than 50 research projects related to TB. Other OIs NIAID-supported scientists also study other OIs including fungal infections, herpes simplex virus infections, toxoplasmosis and cryptosporidium infections. ----------------------------------------------------------------------- ------- Question 4.3. Guide to Social Security Benefits. U.S. Department of Health and Human Services Social Security Administration SSA Publication No. 05-10020 September 1993 A Guide to Social Security and SSI Disability Benefits For People With HIV Infection About This Booklet Social Security can provide a lifeline of support to people with HIV infection. That lifeline comes in the form of monthly Social Security disability benefits and Supplemental Security Income payments, Medicare and Medicaid coverage, and a variety of other services available to people who receive disability benefits from Social Security. If you are disabled because of HIV infection, this booklet will help you understand the kinds of disability or Supplemental Security Income programs. What's Inside Part 1 -- Background Information The first section provides some brief background information about HIV infection and Social Security. Part 2 -- What Benefits Are You Eligible For? This section explains the nonmedical rules and eligibility factors for Social Security Disability Insurance benefits and Supplemental Security Income Disability payments. Part 3 -- How Does Social Security Define "Disability?" This section explains Social Security's definition of "disability" and how it relates to claimants with HIV infection. Part 4 -- How Does Social Security Evaluate Your Disability This section explains how Social Security evaluates disability claims involving HIV diseases in general. And it includes up-to- date information about the way we process claims, especially those involving women and children with HIV infection. Part 5 -- How Do You File For Disability Benefits? This section includes information about when and how to apply for disability, what steps we take to ensure that your claim is processed quickly and accurately, and most important, what things you can do to help the process along. Also included is information about situations when we can presume a person is disabled and make immediate payments. Part 6 -- Helping You Return To Work This section provides an overview of special rules designed to help you return to work. Part 7 -- What you Need To Know About Medicaid And Medicare This section includes a brief overview of the kinds of benefits available from the Medicaid and Medicare programs. For More Information ***************************************************************** PART 1 -- BACKGROUND INFORMATION Acquired immunodeficiency syndrome (AIDS) is characterized by the inability of the body's natural immunity to fight infection. It is caused by a retrovirus known as human immunodeficiency virus, or HIV. Generally speaking, people with HIV infection fall into two broad categories: 1) those with symptomatic HIV infection, including AIDS; and 2) those with HIV infection but no symptoms. Although thousands of people with HIV infection are receiving Social Security or Supplemental Security Income disability benefits, we believe there may be others who might be eligible for these benefits. Social Security is committed to helping all men, women, and children with HIV infection learn more about the disability programs we administer. And if you qualify for benefits, we are just as committed to ensuring that you receive them as soon as possible. You should also be aware that the Social Security Administrations's criteria for evaluating HIV infection are not linked to the Centers for Disease Control's (CDC) definition of AIDS. This is because the goals of the two agencies are different. CDC defines AIDS primarily for surveillance purposes, not for the evaluation of disability. PART 2 -- WHAT BENEFITS ARE YOU ELIGIBLE FOR? We pay disability benefits under two programs: Social Security Disability Insurance, sometimes referred to as SSDI, and Supplemental Security Income, often called SSI. The medical requirements are the same for both programs, and your disability is determined by the same process. However, there are major differences in the nonmedical factors, which are explained in the next two sections. Social Security Disability Insurance Benefits: The Nonmedical Rules Of Eligibility Here are examples of how people qualify for SSDI: o Most people qualify for Social Security disability by working, paying Social Security taxes, and in turn, earning "credits" toward eventual benefits. The maximum number of credits you can earn each year is 4. The number of credits you need to qualify for disability depends on your age when you become disabled. Nobody needs more than 40 credits and young people can qualify with as few as 6 credits. o Disabled widows and widowers age 50 or older could be eligible for a disability benefit on the Social Security record of a deceased spouse. o Disabled children age 18 or older could be eligible for dependent's benefits on the Social Security record of a parent who is getting retirement or disability benefits, or on the record of a parent who has died. (The disability must have started before age 22.) o Children under the age of 18 qualify for dependents benefits on the record of a parent who is getting retirement or disability benefits, or on the record of a parent who has died, merely because they are under age 18. For more information about Social Security disability benefits in general, ask Social Security for a copy of the booklet, Disability (Publication No. 05-10029). How Much Will Your Benefits Be? How much your Social Security benefit will be depends on your earnings history. Generally, higher earnings translate into higher Social Security benefits. You can find out how much you will get by contacting Social Security and asking for an estimate of your benefits. We'll give you a form you can use to send for a free statement that contains a record of your earnings and an estimate of your benefits. In addition to checking your benefit, we encourage you to use this statement to verify that your earnings have been properly recorded in our files. It's important that you do this because any missing or unreported wages could lower your Social Security benefit or even prevent you from qualifying for disability benefits. If you find a problem, contact your local Social Security office right away, show them proof of your actual wages, and the record will be corrected. This can be particularly important for people who have tested positive for HIV but have not developed symptoms, so that any potential benefits will not be delayed by wage correction efforts. Disabled widows, widowers, and children eligible for benefits as a dependent on a spouse's or parent's Social Security record receive an amount that is a percentage of the worker's Social Security benefit. Supplemental Security Income: The Nonmedical Rules Of Eligibility SSI is a program that pays monthly benefits to people with low incomes and limited assets who are 65 or older, or blind, or disabled. As its name implies, "Supplemental" Security Income "supplements" a person's income up to a certain level that can go up every year based on cost-of-living adjustments. The level varies from one state to another, so check with your local Social Security office to find out more about SSI benefit levels in your state. We don't count all the income you have when we figure out if you qualify for SSI. And if you work, there are special rules we use for counting your wages. Again, check with Social Security to find out if you can get SSI. In addition to rules about income, people on SSI must have limited assets. Generally, individuals with assets under $2000, or couples with assets under $3000, can qualify for SSI. However, when we figure your assets, we don't count such items as your home, your car (unless it's an expensive one), and most of your personal belongings. Your Social Security office can tell you more about the income and asset limits. For more general information, ask for a copy of the booklet, SSI (Publication No. 05-11000). PART 3 -- HOW DOES SOCIAL SECURITY DEFINE DISABILITY? In this section, we'll explain the criteria you must meet in order to be considered "disabled." First, we'll explain in general terms how Social Security defines and determines disability. Then we'll discuss how it applies to people with HIV infection. The General Definition Of Disability Disability under Social Security is based on your inability to work because of a medical condition. You will be considered disabled if you are unable to do any kind of "substantial" work for which you are suited. (Usually, monthly earnings of $500 or more are considered substantial.) Your ability to work must be expected to last at least a year. Or, the condition that keeps you from working must be so severe that you are not expected to live. For children, we decide how the condition affects their ability to function--to do the things and behave in the ways that other children of the same age normally would. How This Definition Of Disability Applies To People With HIV Infection A person with symptomatic HIV infection is often severely limited in his or her ability to work. In other words, if the evidence shows that you have symptomatic HIV infection that severely limits your ability to work, and if you meet the other eligibility factors, the chances are very good that you will be able to receive Social Security or SSI Benefits. On the other hand, some people with HIV infection may be less impaired and able to work, so they may not be eligible for disability. PART 4 -- HOW DOES SOCIAL SECURITY EVALUATE YOUR DISABILITY? Social Security works with an agency in each state, usually called a Disability Determination Service (DDS), to evaluate disability claims. At the DDS, a disability evaluation specialist and a doctor follow a step-by-step process that applies to all disability claims, thus assuring a consistent approach to evaluating disability. First, the DDS specialists decide whether your impairment is "severe." This simply means the evidence must show that your disability interferes with your ability to work. The next step in the process is deciding whether the disability is included in a list of impairments. This list describes, for each of the major body systems, impairments that are considered severe enough to prevent an adult from doing any substantial work or in the case of children under the age of 18, impairments that are severe enough to prevent a child from functioning in a manner similar to other children of the same age. Recently we published a list of impairments for HIV infections. In this list, we have included many conditions associated with symptomatic HIV infection, including some that specifically apply to women and children with HIV infection (See next two sections). Some of the HIV-related conditions included in the HIV list of impairments are shown below. The level of severity that an impairment must meet to be found disabling are also specified in the regulations. o Pulmonary tuberculosis resistant to treatment o Kaposi's sarcoma o Pneumocystis carinii pneumonia (PCP) o Carcinoma of the cervix o Herpes Simplex o Hodgkin's disease and all lymphomas o HIV Wasting Syndrome o Syphilis and Neurosyphilis o Candidiasis o Histoplasmosis Remember: these are just a few examples. You can see a complete list of HIV-related impairments at any Social Security office. The complete list will also include the findings necessary for listed impairments to be considered disabling by Social Security. If you have symptoms of HIV infection that are not specifically included in (or equal in severity to) the impairments on our list, then DDS disability specialists will look at how frequently these conditions occur and how they affect your ability to function. The DDS team will evaluate how well you function in three general areas: daily activities; social functioning; and the ability to complete tasks in a timely manner, which requires the ability to maintain concentration, persistence, and pace. If you have "marked limitations" in any one of these functional areas and repeated manifestations of HIV meeting the criteria in the listings, you may be found disabled. A marked limitation is one that seriously interferes with your ability to function independently, appropriately, and effectively. It does not mean that you must be confined to bed, hospitalized, or in a nursing home. If the specialists decide that you are not disabled at this point because you do not have a condition that exactly matches or is equal in severity to one on our list, then they will look to see if your condition prevents you from doing the work you normally do. If it does not, then we look to see if it prevents you from doing any other type of work you're suited for, based on your age, education, and experience. If it does, you may still be found disabled. Remember, at all steps in the process, your impairment must be documented. Documentation includes medical records from your doctors, as well as laboratory test results, X-ray reports, etc. The HIV infection itself--that is, the presence of the virus--must be documented as well as any HIV-related manifestations. At all steps in the process it is important that we have evidence of signs, symptoms, and laboratory findings associated with HIV infection, as well as information on how well you are able to function day-to-day. The signs and symptoms may include: repeated infections; fevers/night sweats; enlarged lymph nodes, liver or spleen; lower energy or generalized weakness; dyspnea on exertion; persistent cough; depression/anxiety; headache; anorexia; nausea and vomiting; and side effects of medication and/or treatment, as well as how your treatment affects your daily activities. Evaluation Of HIV Infection In Women Statistics show that there is an increasing number of women with HIV diseases. Social Security's guidelines for the immune system recognize that HIV infection can show up differently in women than in men. In addition to following the criteria outlined in the previous section, DDS disability evaluators consider specific criteria for diseases common in women. These include: vulvovaginal candidiasis (yeast infection); genital herpes; pelvic inflammatory disease (PDI); invasive cervical cancer; genital ulcerative disease; and condyloma (genital warts caused by the human papillomavirus). Again, the level of severity necessary for these impairments to be considered disabling is included in the list of impairments. Evaluation Of HIV Infection In Children We also have separate listings for children with HIV infection. These guidelines recognize the fact that the course of the disease in children can differ from adults. As with adults, some children may not appear to have the conditions specified in the guidelines, or may have listed conditions that are not as severe as the guidelines require. When this happens, a functional assessment is made using criteria contained in the lists. A child may be disabled if the HIV-related impairments substantially reduce his/her ability to grow, develop, or engage in activities similar to children of the same age. For more information about disability benefits for children, ask Social Security for a copy of the booklet, Social Security And SSI Benefits For Children With Disabilities (Publication No. 05- 10026). PART 5 -- HOW DO YOU FILE FOR DISABILITY BENEFITS You apply for Social Security and SSI disability benefits by calling or visiting any Social Security office. All Social Security files are kept strictly confidential. It would help if you have certain documents with you when you apply. But don't delay filing because you don't have all the information you need. We'll help you get the rest of it after you sign up. The information you'll need may include: o your Social Security number and birth certificate; o the Social Security numbers and birth certificates for family members signing up on your record; and o a copy of your most recent W-2 form (or your tax return if you're self-employed). If you're signing up for SSI, you will need to provide records that show that your income and assets are below the SSI limits. This might include such things as bank statements, rent receipts, care registration, etc. You'll also need to give us information about how your condition affects your daily activities, the names and addresses of your doctors and clinics where you've received treatment, and a summary of the kind of work you've done in the last 15 years. If you have medical evidence such as reports of blood tests, laboratory work, or a physical, it would be helpful if you brought them with you. In the section below (What You Can Do to Expedite the Processing of Your Claim), we give you some guidelines for providing us with medical and vocational information that will help speed up your claim. But first, we want you to know what Social Security does to make the process work as smoothly as possible. What Steps Has Social Security Taken To Ensure Prompt Processing And Payment Of Disability Benefits? All HIV infection claims are given prompt attention and priority handling. For many people applying for SSI with a medical diagnosis of symptomatic HIV infection, the law allows us to PRESUME they are disabled. This permits us to pay up to 6 months of benefits pending a final decision on the claim. You will qualify for this immediate payment if: o a medical source confirms that the HIV infection is severe enough to meet SSA's criteria; o you meet the other SSI nonmedical eligibility requirements; and o you are not doing "substantial" work (See section, "The General Definition of Disability" in Part 3). If you have symptomatic HIV infection but the local Social Security office cannot provide immediate payment, a disability evaluation specialist at the DDS may still make a "presumptive" disability decision at any point in the process where the evidence suggests a high likelihood that your claim will be approved. (If we later decide you are not disabled, you will NOT have to pay back the money you received.) Special arrangements have been made with a number of AIDS service organizations, advocacy groups, and medical facilities to help us get the evidence we need to streamline the claims process. And many DDS's have Medical/Professional Relations Officers who work directly with these organizations to make this process work smoothly. What You Can Do To Expedite The Processing Of Your Claim You can play an active and important role in ensuring that your claim is processed accurately and quickly. The best advice we can give you is to keep thorough records that document the symptoms of your illness and how it affects your daily activities, and then to provide all of this information to Social Security when you file your claim. Below are some guidelines you can follow: o Document the symptoms of your illness early and often Use a calendar to jot down brief notes about how you feel on each day. Record any of your usual activities you could not do on any given day. Be specific. And don't forget to include any psychological or mental problems. o Help your doctor help you Not all doctors may be aware of all the kinds of information we need to document your disability. Ask your doctor or other health care professional to track the course of your symptoms in detail over time and to keep a thorough record of any evidence of fatigue, depression, forgetfulness, dizziness, and other hard-to-document symptoms. o Keep records of how your illness affected you on the job If you were working, but lost your job because of your illness, make notes that describe what it is about your condition that forced you to stop working. o Give us copies of all these records when you file In addition to these records, be sure to list the names, addresses, and phone numbers of all the doctors, clinics, and hospitals you have been to since your illness began. Include your patient or treatment identification number if you know it. Also include the names, addresses, and phone numbers of any other people who have information about your illness. PART 6 -- HELPING YOU RETURN TO WORK If you return to work, Social Security has a number of special rules, called "work incentives," that provide cash benefits and continued Medicare or Medicaid coverage while you work. They are particularly important to people with HIV disease who, because of the recurrent nature of HIV-related illnesses, may be able to return to work following periods o disability. The rules are different for Social Security and SSI beneficiaries. For people getting Social Security disability benefits, they include a 9-month "trial work period" during which earnings, no matter how much, will not affect benefit payments; and a 3-year guarantee that, if benefits have stopped because a person remains employed after the trial work period, a Social Security check will be paid for any month earnings are below the "substantial" level (generally $500). In addition, Medicare coverage extends through the 3-year timeframe after the trial work period, even if your earnings are substantial. SSI work incentives include continuation of Medicaid coverage even if earnings are too high for SSI payments to be made, help with setting up a "plan to achieve self-support" (PASS), and special consideration for pay received in a sheltered workshop so that SSI benefits may continue even though the earnings might normally prevent payments. These and other work incentives are explained in detail in the publication, Working While Disabled...How Social Security Can Help (Publication No. 05-10095). For a free copy, just call or visit your nearest Social Security office. PART 7 -- WHAT YOU NEED TO KNOW ABOUT MEDICAID AND MEDICARE Medicaid and Medicare are our country's two major government-run health insurance programs. Generally, people on SSI and other people with low incomes qualify for Medicaid, while Medicare coverage is earned by working in jobs covered by Social Security, for a railroad, or for the federal government. Many people qualify for both Medicare and Medicaid. Medicaid Coverage In most states, Social Security's decision that you are eligible for SSI also makes you eligible for Medicaid coverage. (Check with your local Social Security or Medicaid office to verify the requirements in your state.) State Medicaid programs are required to cover certain services, including inpatient and outpatient hospital care and physician services. States have the option to include other services, such as intermediate care, hospice care, private duty nursing, and prescribed drugs. For more information about Medicaid, contact your local Medicaid agency. Medicare Coverage If you get Social Security disability, you will qualify for Medicare coverage 24 months after the month you became entitled to those benefits. Medicare helps pay for: o inpatient and outpatient hospital care; o doctor's services; o diagnostic tests; o skilled nursing care; o home health visits; o hospice care; and o other medical services. For more information about Medicare, call or visit your local Social Security office to ask for the booklet Medicare (Publication No. 05-10043). FOR MORE INFORMATION For more information or to apply for benefits, call or visit Social Security. It's easiest to call Social Security's toll-free telephone number. The number is 1-800-772-1213. You can speak to a representative 7 a.m. to 7 p.m. each business day. The best times to call are early in the morning, early in the evening, late in the week, and toward the end of the month. The Social Security Administration treats all calls confidentially--whether they're made to our toll-free numbers or to one of our local offices. We also want to ensure that you receive accurate and courteous service. That's why we have a second Social Security representative monitor some incoming and outgoing telephone calls. Note from the AIDS Information Center: This document reflects changes in Social Security rules that took effect on July 2, 1993 and, also, how SSA evaluates claims based on HIV/AIDS. Copies of this publication, available in English and Spanish, can be ordered through Social Security's toll-free number, 1-800-772-1213. The publication numbers are 05-10020 (English) and 05-10920 (Spanish). For bulk quantities call the Public Information Distribution Center at (410) 965-0945. The fax number for ordering publications is (410) 965-0696. ----------------------------------------------------------------------- ------- Question 4.4. What if you can't afford AZT? PATIENT ASSISTANCE PROGRAM AT BURROUGHS WELLCOME The Burroughs Wellcome Company has announced changes in its Patient Assistance Program (PAP) to make access to its drugs easier for disadvantaged patients. Physicians can now call a toll-free number, once they have determined that a patient is in need, to receive authorization to enroll the patient in the program. Upon authorization, the physician will give the patient a prescription benefit card from PCS Health Systems that can be used at any pharmacy. To qualify, patients must meet the following guidelines: o be a resident of the United States or its territories; o be financially disadvantaged; o have applied for and be awaiting reply from other prescription funding sources; or o not qualify for private or government assistance. The primary patient groups expected to participate are those using Burroughs Wellcome products for HIV and related infections, those with herpesvirus infections, transplant recipients, and those with cancer or congestive heart failure. Enrollment in the PAP must be initiated by a physician. To find out if an individual is eligible, patients should have their physicians call (800) 722-9294. ----------------------------------------------------------------------- ------- Question 4.5. What about DNCB? DNCB FACT SHEET Billi Goldberg PURPOSE DNCB (1-chloro-2,4-dinitrobenzene or C(6)H(3)ClN(2)O(4)) is a potent topical contact sensitizer. Studies have shown that, when used regularly, DNCB will boost the cellular immune response resulting in increased numbers of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells . REFERENCES Caulfield CR, Goldberg B. 1993. The Anarchist AIDS Medical Formulary. Berkeley: North AtlanticBooks. Gilden D. DNCB Treatment Today. AIDS Treatment News #182 1993:3-7. Hosein S. Immunomodulators. Treatment Update #43 1993;4(3):4-6. Mills LB. Stimulation of T-cellular immunity by cutaneous application of dinitrochlorobenzene. J Am Acad Dermatol 1986;14(6):1089-1090. Stricker RB, Elswood BF, Abrams DI. Dendritic cells and dinitrochlorobenzene (DNCB): a new treatment approach to AIDS. Immunol Lett 1991;29:191-196. Stricker RB, Elswood BF. Topical dinitrochlorobenzene in HIV disease. J Am Acad Dermatol 1993;28(5):796-797. Stricker RB et al. Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection. Immunol Lett 1993;36:1-6. ACTION The mechanism of immunological action of DNCB is due to Delayed Type Hypersensitivity (DTH) which involves the initiation of the Th1 or the cell mediated immune response (CMI). The humoral or antibody system is not directly involved in DTH. The primary infections in AIDS are of an intracellular nature which can only be controlled by the cell mediated immune response; the antibody system is ineffective in controlling these opportunistic infections. DRUGS AND IMMUNOSUPPRESSION Antibiotics, nucleosides analogues and other drug treatments can interfere with the cell-mediated immune response thus negating the systemic action initiated by DNCB. Drugs required for the treatment of infections must be continued until the infections are cleared or controlled. Individuals with AIDS must use PCP prophylaxis; use of other prophylaxis drugs is of questionable value (see Hoover DR et al. 1993. Clinical manifestations of AIDS in the era of pneumocystis prophylaxis. NEJM 329:1922-1926) especially in DNCB users. It is extremely important to avoid all forms of ultraviolet radiation such as sunlight (wear a hat and use sunblockers) and tanning salons. UV light not only suppresses cellular immunity but can increase HIV replication. VITAMINS, MINERALS, AND IMMUNITY Individuals with compromised immune systems fighting chronic infections require supplements of basic vitamins, antioxidants, and minerals. Suggested supplements are Multi-mineral tab, Multi-vitamin tab, Beta Carotene (25,000 I.U.), B-Complex, Vitamin C (1000 mg), Vitamin E (400 I.U.), Odorless Garlic (270 mg), and Zinc (60 mg). These supplements can be taken once or twice a day; however, Zinc should only be taken once a day since it can be toxic when over 100 mg per day is used. INFORMATION AND AVAILABILITY DNCB information and kits can be obtained from DNCB Now!, 2261 Market Street, #499, San Francisco, CA 94114 or call (415) 954-8896. Starter kits are available for a suggested donation of $25.00 which includes postage and treatment instructions. Single vials of DNCB require a $6.00 suggested donation which includes postage. For an additional donation of $5.00, an information packet of literature on DNCB and cell-mediated immunity will be sent. DNCB kits, individual vials, and information packets will be supplied free of charge to those unable to afford them. DNCB TREATMENT INSTRUCTIONS (Rev. 12/1/93) by Billi Goldberg PURPOSE DNCB is a potent topical contact sensitizer. Studies have shown that, when used regularly, DNCB will boost the immune response resulting in increased numbers of cytotoxic T-lymphocytes (CTL) and natural killer (NK) cells. Articles and studies in The Anarchist AIDS Medical Formulary,(1) AIDS Treatment News,(2) Treatment Update,(3) and scientific journals(4) provide additional information on DNCB that may be helpful. DRUGS AND IMMUNOSUPPRESSION Antibiotics, nucleosides analogues and other drug treatments can interfere with the cell-mediated immune response and negate the systemic action initiated by DNCB. Drugs required for the treatment of infections must be continued until the infections are cleared or controlled. Drugs taken for prophylaxis purposes or other reasons can impair the immune response and might interfere with the immune boosting properties of DNCB. The need, amount, and dosing schedule for prophylaxis drugs and other treatments that suppress absolute CD8 counts should be given serious consideration.(5) It is strongly recommended that individuals with AIDS prophylaxis against PCP with aerosol pentamidine monthly or co-trimoxazole/Bactrim/Septra or dapsone three times a week. It is extremely important to avoid all forms of ultraviolet radiation such as sunlight (wear a hat and use sunblockers) and tanning salons. UV light not only suppresses cellular immunity but can increase HIV replication. VITAMINS, MINERALS, HERBS AND IMMUNITY Individuals with compromised immune systems fighting chronic infections require supplements of basic vitamins and minerals. Suggested supplements are Multi-mineral tab, Multi-vitamin tab, Beta Carotene (25,000 I.U.), B-Complex, Vitamin C (1000 mg), Vitamin E (400 I.U.), Odorless Garlic (270 mg), and Zinc (30 mg). These supplements should be taken only once a day; overuse of supplements can be detrimental. Zinc can be toxic when over 100 mg per day is used. There are studies that show that the optimal amount of Vitamin C is one to three grams per day with amounts over that causing interference with the immune response.(1) N-acetyl-L-cysteine (NAC) and other anti-oxidants such as curcumin, interfere with lymphocyte proliferation and immunological functions (i.e., IL-2 and IL-2R, cellular adhesion molecules, lymphotoxin, and production of colony stimulating factors) in infected and uninfected cells by inhibiting Nuclear Factor-kappa B (NF-kB).(2) Most herbs are polysaccharides that initiate a systemic antibody response or Th2. Studies have shown that activation of this Th2 response will shutdown the cell-mediated immune response (Th1) required to control the infections involved in AIDS. Herbs, therefore, should not be used indiscriminately or on a regular basis unless it can be shown that they initiate cellular immunity or delayed-type hypersensitivity. If the immunological action of any herb is not known, it should not be used. INITIAL APPLICATION (if previous DNCB user, start with 0.2% solution) 1. Using a Q-tip, apply the 10% SOLUTION to the inner LEFT forearm in a 2" x 2"-square. (Do not use with thymic peptides or cytokines.) 2. After a few minutes, apply the Q-tip with the 10% SOLUTION a second time on the same 2" x 2"-square location. 3. Let dry for a few minutes and cover with a large adhesive bandage, making certain that the adhesive does not touch the application site. Do not remove bandage or wash the application site for at least ten hours. 4. Do not, under any conditions, apply DNCB again until two weeks has elapsed even if there is no reaction at the application site. AFTER TWO WEEKS 1. Using a Q-tip, apply the 2% SOLUTION to the inner RIGHT forearm in a 2" x 2"-square. 2. After a few minutes, apply the Q-tip with the 2% SOLUTION a second time on the same 2" x 2"-square location. 3. Let dry for a few minutes and cover with a large adhesive bandage, making certain that the adhesive does not touch the application site. Do not remove bandage or wash the application site for at least ten hours. 4. In less than seventy-two hours, the skin at the application site should be bright red, itchy, and slightly raised. If this happens, start weekly applications as per the next section. 5. If there is no reaction, continue with weekly applications of the 10% SOLUTION (alternating arms each week) until there is an appropriate response at the application site, then start weekly applications. AFTER ONE WEEK AND EACH WEEK THEREAFTER 1. Repeat numbers 1 to 4 above using the 2% SOLUTION, using a different application site for each weekly application. Stinging at the site within one hour after application is a sign of an appropriate dose that will result in a good reaction, but this does not occur in all individuals. 2. It is advisable to move the application site each month between the inner arms, inner thighs, and trunk (stomach, rib cage, and chest). It is especially important to apply DNCB on the upper and lower trunk areas more often that other sites, since the lungs and gastrointestinal tract are primary sources of opportunistic infections. When applying to the trunk area, use a 3" x 3"- square. Every six weeks or more often if there are infections, it is advisable to use extra DNCB by applying the Q-tip one additional time to the trunk area application site. To initate an increased immune response, DNCB can be applied to more than one site during the weekly application (such as two trunk sites, arm and trunk, thigh and trunk, neck and trunk, etc.). It can also be applied at or near swollen lymph nodes. 3. If the application site is not bright red and slightly raised in twenty-four to seventy-two hours, the solution is too weak. For the next application, either increase the solution strength or apply one extra application with the Q-tip. 4. If the skin at the application site has raised blisters or open sores, decrease the strength of the application by either applying only once with the Q-tip, or using a weaker solution, such as 0.2% or 0.02%. 5. If the present application site becomes bright red in twenty-four to seventy-two hours or any previous application site changes color, you are considered sensitized and need only to continue applications on a weekly basis. 6. Do not use DNCB more than once a week, no matter what conditions or circumstances occur. If severe contact dermatitis or itching occurs, apply calamine lotion, aloe vera, cocoa butter, or Bactine directly to the rash. The use of cortisone or hydrocortisone creams is not recommended, as they have systemic immunosuppressing effects. An overly strong reaction resulting in dermatitis is a sign of an excellent immune response and is positive not negative. The dermatitis will heal in time and will not leave a scar. DNCB can be applied to Kaposi's sarcoma lesions at the same time as the weekly application. DNCB must be used weekly to be effective and to initiate appropriate systemic immune responses. REFERENCES (1) Caulfield CR, Goldberg B. 1993. The Anarchist AIDS Medical Formulary. Berkeley, CA: North Atlantic Books. (2) Gilden D. 1993. DNCB Treatment Today. AIDS Treatment News 182:3-7. (3) Hosein S. 1993. Immunomodulators. Treatment Update 43 :4(3):4-6. (4) Mills LB. 1986. Stimulation of T-cellular immunity by cutaneous application of dinitrochlorobenzene. J Amer Acad Dermatol 14:1089-1090; Stricker RB, Elswood BF, Abrams DI. 1991. Dendritic cells and dinitrochlorobenzene (DNCB): a new treatment approach to AIDS. Immunol Lett 29:191-196; Stricker RB, Zhu YS, Elswood BF. et al. 1993. Pilot study of topical dinitrochlorobenzene (DNCB) in human immunodeficiency virus infection. Immunol Lett 36:1-6; and Stricker RB, Elswood BF. 1993. Topical dinitrochlorobenzene in HIV disease. J Am Acad Dermatol 28:796-797. (5) Hoover DR, Saah AF, Bacellar H., et al. 1993. Clinical manifestations of AIDS in the era of pneumocytstis prophylaxis. NEJM 329:1922-1926; and Osmond D, Charlebois E, Lang W. et al. 1994. Changes in AIDS survival time in two San Francisco cohorts of homosexual men, 1983 to 1993. JAMA 271:1083-1087. (6) Munster AM, Loadholdt CB, Leary AG, Barnes MA. 1977. The effect of antibiotics on cell-mediated immunity. Surgery 81:692-695; Anderson R, Oosthuizen R, Maritz R, et al. 1980. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr 33:71-76; and Ramirez I, Richie E, Wang YM, van Eys J. 1980. Effect of ascorbic acid in vitro on lymphocyte reactivity to mitogens. J Nutr 110:2207-2215. (7) Aillet F, Gougerot-Pocidalo MA, Virelizier JL, Israel N. 1994. Appraisal of potential therapeutic index of antioxidants on the basis of their in vitro effects of HIV replication in monocytes and interleukin 2-induced lymphocyte proliferation. AIDS Res Hum Retro 10(4):405-411; Staal FJT, Roederer M, Raju PA, et al. 1993. Antioxidants inhibit stimulation of HIV transcription. AIDS Res Hum Retro 9;299-306; Nabel GJ. 1993. The role of cellular transcription factors in the regulation of human immunodeficiency virus gene expression. In: Cullen BR, ed. 1993. Human Retroviruses, New York: IRL Press, 61; Go C, Miller J. 1992. Differential induction of transcription factors that regulate the interleukin 2 gene during anergy induction and restimulation. J Exp Med 175:1327-1336; and Baeuerle PA, Henkel T. 1994. Function and activiation of NF-kB in the immune system. Ann Rev Immunol 12:141-179. HOW DNCB WORKS by Billi Goldberg DNCB is applied weekly on the skin at various sites which initiates contact sensitivity. The Langerhans cells in the skin at the application site pick up the DNCB antigen, migrate from the skin, change into veiled dendritic cells, continue their migration to the nearest lymph node, change into interdigitating dendritic cells. Once in the lymph nodes, they present the DNCB antigen to CD4 helper cells, thus initiating a Th1 response or cell mediated immune response or Type IV Delayed Type Hypersensitivity response (they can all be considered the same thing). The CD4 helper cells then proliferate forming more helper CD4 cells which then circulate and activate effector cells (primarily macrophages) to rid the sysem of the DNCB antigen. At the same time CD4 memory cells are produced adding to the CD4 memory pool for the DNCB antigen (hapten). Each time DNCB is applied, these memory cells are activated thus initiating a systemic Th1 response to DNCB. The longer DNCB is used, the response becomes faster, more potent, and more effective because there are more circulating DNCB CD4 memory cells to initiate the immune response. The result of this specific systemic Th1 response to DNCB is the non-specific activation of macrophages. Many of these macrophages are infected with HIV and other intracellular pathogens that cause AIDS but are unable to present these pathogen antigens due to infection. The microbial pathogens of AIDS are of the facultative or obligate intracellular type. The activation of these macrophages result in phagocytosis of the pathogens which are then presented by macrophages to CD4 and CD8 memory cells specific for the presented pathogen. The activated helper and cytotoxic T lymphocytes initiate specific systemic responses to destroy the presented pathogens. This results in more activated macrophages, more pathogens presented, more T memory cells activated, more infected cells destroyed, ad infinitum. Since pathogens can be presented on both the Class I and Class II MHC (major histocompatibility complex) of the antigen presenting cells, cytotoxic T lymphocytes, natural killer cells, neutrophils, and killer macrophages are also activated to accomplish the destruction. There is also an excellent probability that dendritic cells (the most potent antigen presenting cells in the immune system) are also activated in the lymphoid tissues to present intracellular and extracellular antigens thereby activating even more T lymphocyte memory, helper, and effector cells thus increasing the Th1 response against the pathogens involved in AIDS. It is extremely important to remember that the antibody/Th2/humoral response is not directly involved in fighting the infections of AIDS. The denial of this fact is the primary reason that there has been no progress in realistic treatments for AIDS. In point of fact, there is research to show that activating the antibody or Th2 response may suppress the Th1 response. This would allow the intracellular pathogens to be uncontrolled since their control depends on the Th1 or cell-mediated immune response. There is also research to show that immune complexes (HIV + antibody) can be internalized through the antibody receptor (Fc) of monocytes and macrophages thus spreading and increasing HIV infection of these cells. Delayed Type Hypersensitivity is an extremely effective and potent immune modulator that forces priming and activation of macrophages that are non-responsive due to infection. DNCB, then, acts like an adjuvant or biological response modifier. These phenomena have been researched in-depth and are considered a factual part of scientific knowledge. On page 1292 of the recent edition of The Merck Manual is the following: "Skin malignancies have regressed after induction of delayed hypersensitivity to dinitrochlorobenzene (DNCB) and subsequent direct application of DNCB to the tumor." Below are the scientific explanations of what happens. This process has been an integral part of the scientific literature for many years. Meltzer and Nacy have explained it brilliantly. DNCB is not new; it has been used for decades. But, since the cost of DNCB is minimal and there is no profit to be made, it has been ignored. The following is from Chapter 28 titled "Delayed-Type Hypersensitivity and the Induction of Activated, Cytotoxic Macrophages" by Monte S. Meltzer and Carol A. Nacy in Fundamental Immunology (1989), second edition, published by Raven Press. Page 775: "Contact sensitivity is a variant form of DTH in which certain reactive chemicals (usually small molecular weight compounds or metal ions that can diffuse into the epidermis) covalently bind to skin proteins and create neoantigens. Such neoantigens prime or sensitize the exposed animal to a second cutaneous application of the reactive chemical (contactant). A portion of the neoantigen is host derived. Thus an animal exposed to trinitrochlorobenzene (TNCB or picryl chloride) solution epicutaneously responds to a repeated cutaneous exposure with a vigorous DTH response. Intradermal injection of TNCB covalently bound to an irrelevant protein such as albumin fails to elicit this response. Neoantigens induced in the epidermis are taken up by Langerhans cells. These highly efficient, antigen-presenting dendritic cells migrate into the dermis, enter lymphatics, and travel to the cortical region of the draining lymph node where they present the antigen to CD4+ T cells. Application of normally sensitizing chemicals to skin devoid of Langerhans cells (skin treated with corticosteroids, UVB light, or cellophane adhesive tape) does not induce contact sensitivity and may produce specific immunologic tolerance to the contactant." Pages 766-767: "Coincident with the development of DTH during infection is a widespread activation of free and fixed mononuclear phagocytes throughout the body. Tissue macrophages develop profound alterations in morphology, cell proliferation, phagocytosis, and the capacity to destroy intracellular and extracellular microorganisms. Each of these changes is dependent on interactions with sensitized lymphocytes. These systemic changes in the antimicrobial activity of immunologically activated macrophages may explain observations made as early as 1936 that animals responding to reinfection with one microorganism (bacterium A) [ed. DNCB] acquire the ability to resist nonspecifically infection with antigenically unrelated pathogens (bacterium B, C, or D). Unlike the long-lived, antigen specific, DTH response, this nonspecific element of acquired resistance is short lived and can only be reexpressed by further exposure to the original microbe (bacterium A) [ed. DNCB]. "Thus the DTH response to foreign antigens induces a series of immune reactions whose ultimate purpose is the short-term accumulation of nonspecifically cytotoxic, macrophage effector cells. Mononuclear phagocytes rapidly and preferentially accumulate at sites of infection. These inflammatory cells co-locate with antigen-reactive, sensitized T cells and undergo dramatic changes in their functional state. The activated macrophages that result are pleuripotent cytotoxic effector cells which destroy viruses, bacteria, fungi, single and multicellular parasites, allografts, and tumor cells. This complex network of cell-mediated reactions is controlled by an even more complex interaction of various cytokines, those released by the T cell, the macrophage, and even the target cell. DTH reactions are not self-destructive overreactions to foreign antigens, but rather tightly controlled body defenses against tissue allografts, infection, and neoplastic change." ----------------------------------------------------------------------- --------------------------- Question 4.6 Alternative Treatments (please contribute) OZONE THERAPY (Part I) Ozone Therapy: The Science Behind the Scandal Ozone therapy, involving doses of the reactive oxygen gas, has long been in Europe a popular alternative treatment for a variety of ailments. While health authorities chide practitioners for using this "unproven" therapy, reports continue to describe favorable results. Scientists also continue to investigate the potential of ozone therapy to eliminate disease-causing organisms from the bloodstream. In the mid-1980s, German researchers began using a process called autohemotherapy to test the use of ozone on blood infected with HIV and hepatitis B and, in 1986, a biotech company called Medizone International was created to follow up on the approach. Since then, Canadian and American scientists have confirmed ozone's direct antiviral effects, and its ability to boost key parts of the immune system. Last May, a Canadian study reported that ozone completely inactivated SIV, the simian equivalent of HIV, in monkey blood. The implications for safeguarding the blood supply are clear, although the therapeutic potential is not. Nevertheless, according to Medizone, preliminary trials are being conducted at five centers in Italy using an ozone/oxygen mix to treat patients with HIV and hepatitis B. A great deal of research remains to be performed on ozone, but advocates predict that because ozone cannot be patented, it will not attract financial backing for the scientific studies needed to win FDA approval. Longevity (04/94) Vol. 6, No. 5, P. 54. Frankum B. Katelaris CH. Ozone Therapy in AIDS--Truly Innocuous? [letter]. Med J Aust. 1993 Oct 4;159(7):493. Carpendale MT. Freeberg J. Griffiss JM. Does Ozone Alleviate AIDS Diarrhea? J Clin Gastroenterol. 1993 Sep;17(2):142-5. Five patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) and intractable diarrhea were treated with daily colonic insufflations of medical ozone (oxygen/ozone mixture) for 21-28 days. The daily dose of ozone (O3) ranged from 2.7 to 30 mg. Three of the four patients whose diarrhea was of unknown etiology experienced complete resolution, and one patient had marked improvement. The fifth patient, whose diarrhea was due to Cryptosporidium, experienced no change. No consistent change in the absolute number of helper (CD4) or suppressor (CD8) lymphocytes was detected, and no obvious changes were seen in the PO2 or the results of routine hematologic and blood chemistry studies. Patients had mild to moderate local discomfort during ozone administration early in the course of treatment, but no adverse systemic effects were observed. The results of this series suggest that medical ozone administered by rectal insufflation is simple, safe, and effective. Should this simple treatment be used routinely to treat chronic intractable ARC/AIDS diarrhea? Carpendale MT. Griffiss J. Is There a Role for Medical Ozone in the Treatment of HIV and Associated Infections? In: Ozone in Medicine. Proceedings of the Eleventh Ozone World Congress, August 29-September 3, 1993, San Francisco, CA. PP. M-1-32-M-1-45. International Ozone Association, Pan American Committee, 31 Strawberry Hill Ave., Stanford, CT 06902-2608. Medical Oxone inactivates many pathogenic viruses including HIV in vitro. Pilot studies in man suggest positive benefits in the early stages of HIV infection (t-4 cells greater thanf 400). These include incrased T4 and T8 cells, normalizing of T4:T8 ratio, and a general feeling of wellbeing and minimal evidence of infection. Improvement also occurs in AIDS patients (T4 cells less than 200) but less evidence of T4 cell resurgence. These studies indicate that at least in vitro there is a good safety margin between the ozone dose required to inactivate HIV and the earliest suggestion of suppression of lymhocytes. In fact, the lymphocytes are being stimulated at doses that completely inactivates HIV. More work needs to be done to clarify the most effective dosage and means of treating HIV infections with medical ozone. LoLordo, Ann. AIDS Treatment Documentary Premieres Amidst Controversy. PR Newswire, San Francisco, 08/30/93. The medical world [criticized] a documentary about an unapproved medical treatment called ozone therapy, which may allegedly deter cancer and AIDS. Canadian filmmaker Geoffrey Rogers' "Ozone and the Politics of Medicine" [described] a potential breakthrough drug that is dismissed by health officials, although millions of patients in Europe have already used it. Rogers [included] scientific evidence that ozone can inhibit cancer cells and inactivate viruses. A recent study by the Canadian military and the International Red Cross discovered that monkeys injected with blood plasma tainted with SIV, the primate equivalent of the AIDS virus, died within two weeks. Monkeys receiving ozone injections, however, remained healthy and were not infected. The Food and Drug Administration has condemned ozone therapy, and even labeled its use as health care fraud. The drug gained national attention [in July, 1993] when the famous New York doctor Robert Atkins lost his medical license over a complaint about the use of ozone therapy. Dr. Atkins' license was subsequently reinstated. Wolfstadter HD. Sacher J. Hopfenmuller W. Stange R. Retrospective Benefit Following Individualized Naturopathic Therapy in HIV-patients at Different Stages. Int Conf AIDS. 1992 Jul 19-24;8(3):147 (abstract no. PuB 7588). OBJECTIVE: To assess the long-term efficacy and benefit of a complementary treatment regimen, we investigated on laboratory findings and clinical outcome in a cohort of 175 out-patients (CDC II-IV E) successively treated since 1986. METHODS AND PATIENTS: The therapeutic regimen comprised autologous ozone transfusions, homeopathy, phytotherapy, therapy with enzymes, mineral-, vitamin- and trace element substitution, nutritional management, correction of intestinal dysbacteria and psychophysical means, set up on an individualized basis. No conventional antiviral therapy was given. Patients (all male homosexuals) were divided into 5 groups (Gr. I-V) according to their CD4 lymphocyte counts at entry into therapy (Gr.I n = 22, CD4 0-50; Gr. II n = 12, CD4 51-100; Gr. III n = 17, CD4 101-200; Gr. IV n = 81, CD4 201-500; Gr. V n = 53, CD4 greater than 500 [/microliters]) and 15 hematological and biochemical parameters were evaluated with individual regression analysis according to the length of observation of patients (min. obs.time in Gr. I-III 3 months, min. obs.time in Gr. IV and V 6 months). Moreover we studied the incidence and severity of opportunistic infections and overall QOL during the observed period. RESULTS: Patients in Gr. I presented a median loss of CD4 lymphocytes per month of 0.54 cells/microliters(range -42.0 to 4.50, median obs.time 8 months), Gr. II median loss 3.65 cells/microliters (range -5.9 to 8.8, median obs.time 10.5 mo.), Gr. III median loss 4.98 cells/microliters (range -13.5 to 11.0, median obs.time 16.8 mo.). In Gr. V, apparently due to the earlier stage of disease, no clear statistical trend of helper-cell deterioration could be observed. Patients in Gr. IV, with an approved indication for antiviral therapy, presented a median loss of CD4-cells of 4.47/microliters (range -17.2 to 37.5, median obs.time was 25.4 mo.). Compared to CD4 lymphocyte deterioration given in the literature for patients under antiviral therapy, 52% of our patients in Gr. IV exceeded these values, while 24.6% remained below. No substantial adverse events or side effects accompanied the therapies, thus we found QOL generally increased. CONCLUSIONS: Our results suggest that patient performance under a combined and individualized naturopathic regimen might be to some extend improved with respect to data collected from cohorts in the literature. Further investigation including controlled clinical trials on different aspects of the single therapies is necessary. Brown, David. A New Look at Alternative Therapies. Washington Post (Health), 06/23/92, P. 8. The National Institutes of Health will soon examine alternative therapies more closely because of the possible efficacy of the treatments. John C. Pittman, a physician in Raleigh, N.C., discontinued his ozone gas therapy for AIDS patients after the North Carolina Board of Medical Examiners told him they were looking into his controversial practices. However, an advisory board at the NIH last week expressed interest in Pittman's work and requested more information on his claim that three out of 25 patients with HIV had overcome the virus after having the highly reactive gas inserted into their blood. Ed McCabe, author of a book on unconventional uses of oxygen, also told an NIH panel how ozone treatment had significantly improved the conditions of 300 HIV-positive patients. In ozone therapy, a blood sample can be treated with the gas and returned to the patient, or a small volume of gas can be inserted directly into the vein. Advocates say the procedure should be done twice daily for three weeks to treat HIV infection. The Office for the Study of Unconventional Medical Practices, established after the 1992 federal budget requested that NIH spend at least $2 million on such an effort, will attempt to determine which treatments may be promising and can be tested in conventional experiments. Hooker MH. Gazzard BG. Ozone-Treated Blood in the Treatment of HIV Infection [letter; comment]. AIDS. 1992 Jan;6(1):131. Carpendale MT. Freeberg JK. Ozone Inactivates HIV at Noncytotoxic Concentrations. Antiviral Res. 1991 Oct;16(3):281-92. The inactivation of human immunodeficiency virus (HIV) and cytotoxic properties of ozone-treated serum and serum-supplemented media were examined. The titer of HIV suspensions in human serum was reduced in a dose-dependent manner when treated with total reacted ozone concentrations at a range of 0.5 to 3.5 micrograms/ml-1. Complete inactivation of HIV suspensions was achieved by 4.0 micrograms/ml-1 of ozone in the presence or absence of H-9 cells. In contrast, cellular metabolism, as measured by MTT dye cleavage, and DNA replication, as measured by BUdR incorporation, were enhanced in H-9 cells grown in media treated with quantities of ozone that completely inactivate HIV. The permissively HIV-infected cell line HXB/H-9 was cultured in ozone-treated media for six days with culture supernatants being sampled and assayed on alternate days for HIV p24 core protein. HIV p24 was reduced in all treated cultures compared to control cultures, with an average reduction of 46% [p24]. Wells KH. Latino J. Gavalchin J. Poiesz BJ. Inactivation of Human Immunodeficiency Virus Type 1 by Ozone in vitro. Blood. 1991 Oct 1;78(7):1882-90. A device was designed to deliver a constant source of given concentrations of ozone to fluids containing human immunodeficiency virus type 1 (HIV-1). Ozone was found to inactivate HIV-1 virions in a dose-dependent manner. Greater than 11 log inactivation was achieved within 2 hours at a concentration of 1,200 ppm ozone. Similar concentrations of ozone had minimal effect on factor VIII activity in both plasma and immunoaffinity-purified preparations of factor VIII treated for the same time period. The data indicate that the antiviral effects of ozone include viral particle disruption, reverse transcriptase inactivation, and/or a perturbation of the ability of the virus to bind to its receptor on target cells. Ozone treatment offers promise as a means to inactivate human retroviruses in human body fluids and blood product preparations. Garber GE. Cameron DW. Hawley-Foss N. Greenway D. Shannon ME. The Use of Ozone-Treated Blood in the Therapy of HIV I=fection and Immune Disease: A Pilot Study of Safety and Efficacy [see comments]. AIDS. 1991 Aug;5(8):981-4. The use of ozone therapy is reported to be effective in a variety of viral illnesses, including HIV disease. We performed a phase I study of ozone blood treatments in 10 patients in whom no significant toxicity was observed. Three patients with moderate immunodeficiency showed improvement in surrogate markers of HIV-associated immune disease. A phase II controlled and randomized double-blinded study was initiated comparing reinjection of ozone-treated blood, and reinjection of unprocessed blood for 8 weeks, followed by a 4-week observation period. Ozone had no significant effect on hematologic, biochemical or clinical toxicity when compared with placebo. CD4 cell count, interleukin-2, gamma- interferon, beta 2-microglobulin, neopterin and p24 antigen were also unaffected by both treatment arms. In conclusion, ozone therapy does not enhance parameters of immune activation nor does it diminish measureable p24 antigen in HIV-infected individuals. Mayer C. Soyka. Naber D. [Paranoid hallucinatory psychoses in an HIV infected patient on ozone therapy]. Nervenarzt. 1991 Mar;62(3):194-7. Roder W. Muller WE. Merz H. [Is Ozone Suitable for Sterilization of HIV infected Bones?] Unfallchirurg. 1991 Jan;94(1):50-1. HIV infection can be transferred by blood, blood products and organ transplantation. In traumatic surgery allogeneic bone transplantation is commonly used for reconstruction in severe bone injuries. This technique has been abandoned since the appearance of reports of infections with HIV. In an experimental in vitro study we showed that ozone treatment cannot inactivate HIV in bone for transplantation. Wagner K. Mayers D. Toro L. Baker JR Jr. The Effect of Ozone (03) on Lymphocyte Populations in Normal and HIV1-Infected Blood. Int Conf AIDS. 1989 Jun 4-9;5:656 (abstract no. C.587). OBJECTIVE: Measure the effect of varying 03 concentrations on lymphocytes in whole blood from an uninfected and a Walter Reed Stage 2 HIV1 patient. METHODS: Heparinized whole blood samples were exposed in triplicate to (03) of 20, 40, and 60 ug/ml with an oxygen control. Coded, blinded blood samples were gently agitated for 10 min. and incubated for 1 hr. at 27 C. Mononuclear cells were separated using Ficoll-hypaque gradients and stained for FACS analysis using labelled monoclonal antibodies. RESULTS: 03 had no effect on lymphocyte populations of the uninfected donor as numbers of total T cells, CD4, CD8, and B cell subpopulations did not change. In contrast, there were marked changes in the lymphocyte populations of the HIV positive donor with increasing (03). CONCLUSIONS: Ozone, at concentrations previously shown to inactivate HIV1, may alter lymphocyte surface markers in HIV1 infected patients. Further studies are indicated to examine this effect. ***************************************************************** [Editor's Note: This is the text of a letter from Medizone International Inc. in response to inquiries regarding ozone.] --------------------------------------------------------------- Medizone International Inc 123 East 54th Street, Suite 2H, New York NY 10022 (212) 421-0303 Fax: (212) 888-2798 June 29, 1993 Dear xxxx, Thank you for your letter. At present Medizone International Inc and Medizone Canada Ltd are awaiting US Food and Drug Administration and Canadian Health and Welfare approval, respectively, to commence human clinical trials for the use of the Medizone (R) (ozone/oxygen) drug in the treatment of Acquired Immune Deficiency Syndrome (AIDS). The following is a brief overview of Medizone International Inc's research to date. Acquired Immune Deficiency Syndrome (AIDS) is a condition described in 1981 and found to be caused by a retrovirus (HILV-III/HIV). To date, treatment only affords temporary suppression of the virus. Since the identification of Acquired Immune Deficiency Syndrome (AIDS), researchers have employed many modalities to treat patients with HIV-related disease. In Europe, one modality employed has been an ozone/oxygen mixture. The mixture is introduced into fixed volumes of the patient's blood 'ex vivo'. This procedure has been entitled autohemotherapy, but may be referred to more descriptively as extracorporeal circulation. Anecdotal reports on the results of this work are extremely encouraging. However, in view of the fact that no controlled trials have been performed, these results must be carefully evaluated. In March 1986 Medizone International Inc was created specifically to scientifically evaluate this treatment and bring the technology to market. A series of studies were undertaken to establish: a) the safety of extracoporeal circulation with an ozone/oxygen (Medizone(R)) mixture in a variety of animal models (toxicity studies); b) the effect(s) of ozone/oxygen mixture (Medizone(R)) on a human HIV target cell line, HUT-78; c) the anti-retroviral activity of ozone/oxygen (Medizone(R)) on HIV 'in vitro'; d) the effect of ozone/oxygen (Medizone(R)) in human peripheral blood 'ex vivo'; e) the effect of ozone/oxygen (Medizone(R)) on exogenously HIV-1 'spiked' Factor VIII preparations. The studies and results to date include: a) A preliminary rabbit animal model treated with (ozone/oxygen) Medizone(R) in a manner analogous to the proposed human treatment regime at the Long Island College of Pharmacy suggested no toxicity at concentrations up to ten times the dose proposed in man. b) A limited feline model toxicity study performed at the Cornell Feline Health Centre, Cornell Veterinarian College, Ithaca, to investigate the relative toxicity of Medizone(R) has yielded no detectable toxic effects. c) Cell-free HIV treated with (ozone/oxygen) Medizone(R) resulted in 100% inactivation of the virus while maintaining HUT-78 viability. These studies were performed at the State University of New York at Syracuse under the auspices of Dr Bernard Poiesz. d) Implementation of a patented hollow fibre technology has demonstrated Medizone(R)'s ability to *reduce* intracellular viral expression by greater than 99% while maintaining target cell viability. e) Treatment of human peripheral blood with Medizone(R) revealed hemolysis and coagulation changes well within the standard for re-infusion of packed human blood. These studies were performed at the Mount Sinai School of Medicine in New York, under the auspices of Dr Michael Greenburg. f) Published results (Blood, Vol. 78(7):1882, 1991) involving the treatment by Medizone(R) of Factor VIII preparations exogenously 'spiked' with HIV-1 yielded a minimum (ten) log diminution of viral load while maintaining 90% biological activity of this blood component. g) Investigation with Visna Virus and Feline Intestinal Peritonitis Virus, two lipid enveloped viruses, have been inactivated with measurable lipid peroxides derived from Medizone(R) treatment. h) 'In vitro' inactivation by Medizone(R) of a variety of Simian Immune Deficiency (SIV) variants studied through a multi-agency Canadian government collaboration have paralleled those results published by Poiesz et al. The hypotheses underlying ozone's virucidal activity are based upon the drug's propensity toward lipid peroxidation. Those viruses which are lipid-encapsulated (ie. lentivirus family) are highly susceptible to the direct oxidative effect of ozone, and are thereby inactivated. Data indicate the differential effect on lipid envelope viruses versus those whose lipid capsid composition is minimal. We postulate that ozone will inactivate cell-incorporated viruses by at least two discreet mechanisms: 1) Due to the high degree of lipid peroxidation catalysed by ozone interaction(s), viral binding to specific receptors (ie. HIV to CD4A receptor), whose membranous nature (both viral coat and receptor) implies a finite composition of lipid [including polyunsaturated fatty acids (PUFA)], may indeed be ozone sensitive. Investigations with Rhodamine-labelled HIV, challenged with ozone sensitized HIV virions, have suggested alterations in receptor/ligand binding capacity yielding diminished viral binding. This data suggests that ozone, delivered by hollow fiber technology at antiviral concentrations, does impair HIV's ability to bind to CA4A + target cells. 2) It has been demonstrated that target cells with pro-viral DNA incorporated into its genome have decreased titers of certain protective enzyme systems with respect to oxidative perturbations. In particular, superoxide distumase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) levels are diminished in a number of virally transformed cell lines. Such decreases may render these cells selectively sensitive to the oxidative effects initiated by ozone. It should be noted that ozone's effects are instantaneous with regard to peroxidation and the products of this reaction with cellular membrane lipids (hydroperoxides) are relatively stable and can participate in a host of oxidative (including free-radical) propagating reactions. It is our intention to generate, via ozone's direct activity and product(s) derived through lipid interactions, data to support: a) inactivation of those viruses [ie. HIV, Hepatitis B, non-A and non-B (Hepatitis C)] associated with transfusion associated diseases while maintaining the replacement value of the blood fractionate of interest (ie. plasma proteins, packed red cell preparations and platelets). b) reduction of cell incorporation by virus through impairment of viral-receptor binding; c) inactivation of cell-incorporated virus render them non-viable while maintaining normal target cell viability. The results of experimental work have demonstrated non-toxicity in treating; a preliminary animal rabbit model, human HIV target cells, a limited feline model, human peripheral blood, and Factor VIII preparations exogenously 'spiked' with HIV-1, all with ozone/oxygen mixtures (Medizone(R)). Anti-retroviral was demonstrated at concentrations maintaining HUT-78 viability, as well as Factor VIII biological activity, respectively. On June 2nd, 1993, Medizone International Inc announced the successful completion of the first two phases of a Canadian research project that has demonstrated preliminary scientific evidence supporting the use of the company's blood decontamination technology in a live, primate (monkey) model. In making the announcement, Medizone president, Dr Joseph S Latino said, "To date, the research program has successfully demonstrated that monkeys receiving blood fractioned plasma, purposely infected with a highly virulent strain of Simian Immunodeficiency virus (monkey equivalent to HIV), but treated with Medizone's process, did not demonstrate any signs of infection over the course of the study (35 days). However, all animals receiving similarly infected products without the intervention of Medizone's contamination technology died within 12-14 days." This research project was under the direction of an international collaborative team of scientists representing the Canadian Red Cross, Canadian Departments of Defence and Agriculture, Cornell University Veterinary Medical College, and Medizone Canada Ltd. Please do not hesitate to contact me should you require any additional information. Your sincerely, Katherine M Kalinowski Corporate Secretary