HIV HERALD Publication from the National Treatments Project -- Australian Federation of AIDS Organisations PO Box H274, Australia Square, Sydney NSW, 2000 Australia Tel : (+612) 231 2111 Fax : (+612) 231 2092 November 1994 Volume 4 No 10 CONTENTS BITS AND PIECES >Thalidomide for treating weight loss. >Cancer drug found to benefit people with AIDS related weight loss. >Passive Immune Therapy. >Fusion Toxin News. >Breakthrough in funding for alternative medicine research in the USA. >Searle stops further development of it's protease inhibitor. ANTIVIRAL NEWS >D4T (Stavudine) interim results released at ICAAC. >Merke protease inhibitor results reported at ICAAC. >Side effects of ddC (Zalcitabine, Hivid). >GEM 91 phase I clinical trial results look good. OPPORTUNISTIC ILLNESSES >Clarithromycin as prophylaxis against MAC? >Why do people with HIV develop an allergic reaction to co-trimoxazole? GENE THERAPY >CD8 cells inserted with marker and suicide genes. COMPLEMENTARY THERAPIES >Some suggested complementary treatments. BITS AND PIECES By Ian McKnight-Smith and Alan Strum >Thalidomide for Treating Weight Loss. Tumour Necrosis Factor (TNF) is a cytokine (chemical messenger) of the body that appears to be involved in the process of weight loss in people with HIV. Thalidomide is popping it's head up as a possible treatment to reduce the levels of TNF in people who are losing weight. A small study completed in Mexico City showed an average weight gain of 8% after 12 weeks of treatment, while the placebo group lost an average of 8% during this time. A similar study from Thailand showed a weight gain of 4.5% after 21 days of treatment. The study in Thailand also had participants (50%) in it who had tuberculosis, which also increases the production of TNF in people with HIV. Neither of the trials measured any markers of the immune system or viral load. A trial using thalidomide for weight loss is now starting in the USA. GMHC Treatment Issues, September 1994. >Cancer drug found to benefit people with AIDS related weight loss. A drug that was first developed for ovarian cancer also helps people with AIDS to regain weight, two studies have found. Whether the short term weight gains will translate into longer life expectancy in people with AIDS remains to be shown, according to an editorial accompanying the studies in the Annals of Internal Medicine (September 15 1994). The Food and Drug Administration in the US approved the drug, megestrol acetate, (Megostat) a year ago for AIDS weight loss based on the two studies that have now been published. First developed as a drug to fight cancer in the breast and ovaries, in part because of its ability to block the cancer promoting effects of oestrogen, megestrol acetate also was found to stimulate appetite and weight gain. In Professor Von Roenn's study, involving 271 AIDS patients, almost 60% of those taking megestrol gained at least 2.3 kg in weight compared to 21% of those who received a placebo In the second study, led by researchers from the University of California. People with AIDS receiving the drug gained an average of more than 5.4kg in 12 weeks, while those on placebo actually had a further weight loss. Both studies found that people taking the drug have a better sense of well-being than those who were taking the placebo. Dr Donald Kotler (a co-author of the study) said "a popular belief among people with AIDS is that once the weight loss begins it cannot be reversed and leads to death." and "weight loss is not a foregone conclusion - weight loss can be reversed." Dr. Howard Grossman, a New York City physician who treats many people with AIDS, said severe weight loss in AIDS could be life threatening. "In most cases it had to do with a loss of the appetite," Dr Grossman said. Even before the FDA approved megestrol acetate, he and other doctors who specialise in AIDS had been successfully using the drug to prevent wasting. "Megestrol acetate works well. Five pounds (2.3kg) can make an enormous difference in how well somebody does." Australian Doctor Weekly Oct 21 1994 (For more information see HIV Herald August 1994 (vol 4 No 7) p7-8 >Passive Immune Therapy Passive immune therapy, also known as hyperimmune therapy, is the process where the fluid of the blood (plasma - which contains antibodies and other chemical properties) is taken from health asymptomatic people and is given to people with a declining immune system. A recent report of a one year study has found that passive immune therapy is not harmful and may be helpful to people with CD4 cell counts of between 50 and 200. The group receiving 500ml of plasma per month showed the most benefit with less deaths reported than the placebo group, but this was not considered to be statistically significant. What was considered to be significant was the increase in CD4 cells in this group of 32.7 compared to an average loss of 3.5 cells in the placebo group. There did not appear to be any differences between the groups in opportunistic infections, however a French study has reported that there were 3 times as many AIDS-related illnesses in their placebo group when compared to the treated group. AIDS Treatment News, October 21, 1994 >Fusion Toxin News A preliminary look at the antiviral effects of DAB389IL-2 fusion toxin were recently announced. This study enrolled 22 participants with CD4 counts between 300 and 600 cells and who were P24 antigen positive. The participants were randomised to one of three doses of DAB389; 50,125 and 220 kU/kg/day. The drug was administered intravenously for 5 consecutive days every 21 days for 3 rounds of treatment. The volunteers were all off antiretroviral treatment for at least 28 days before starting this study. Overall CD4 and CD8 counts remained stable during the study and there were no significant anti-HIV effects detected based on measurement of P24 antigen, viral cultures, or on viral burden as measured by quantitative PCR (polymerase chain reaction) test. 20% of the participants reported side effects such as headaches, nightsweats, fever/chills and myalgia. There were also a couple of cases of reversible elevated hepatic transaminase (a liver enzyme). Project Inform, Oct 26 1994 >Breakthrough in Funding for Alternative Medicine in the USA. The National Institute Of Health (NIH) in the USA has given a 3 year grant of $840,000 to Basyr University in Seattle, WA. Basyr University was founded by Naturopaths in 1978 and now offers degrees in naturopathic medicine, acupuncture and Oriental medicine. The University has studied potential naturopathic and alternative therapies to be used for people with HIV for many years. The grant is to be used to set up an Alternative Medicine Centre for research into HIV/AIDS and will be responsible to : - * "research the patterns of use of alternative treatments for AIDS and related conditions. What is the extent of use of different treatments - both prescribed by health care providers, and self-administered? Are people informing their mainstream doctors about what else they are using?" * "screen and evaluate therapies from the field of alternative medicine, including reporting of adverse events." * "train alternative medicine practitioners in the scientific evaluation of their treatments." * "educate the mainstream biomedical community in alternative medical treatment of HIV infection and AIDS." AIDS Treatment News, October 21 1994 >Searle Stops Further Development of its Protease Inhibitor. The Searle protease inhibitor candidate, SC-52151, has been withdrawn from further development after disappointing results from 2 early studies in humans. Eventhough the drug works very well at inhibiting HIV in test tubes, the human studies have shown that the protease inhibitor does not work against HIV in the body. It is thought that a human protein binds to the drug once it is in the body, therefore preventing the drug from being active against HIV. This is a particular problem that seems to be only associated with the Searle protease inhibitor, and not with other protease inhibitors being developed by other pharmaceutical companies. ANTIVIRAL NEWS >D4T (Stavudine) Interim Results Released at ICAAC By Alan Strum D4T, a nucleoside analogue, is currently available through an open access trial in Australia. Some of the first interim results have now been released from a phase III clinical trial, analysing the results of 359 of 822 people with AZT or D4T. The results were presented by Bristol-Myers Squibb at the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Orlando, Florida USA. In this trial all people had already been receiving AZT for an average of approximately 22 months. Approximately 50% of people in the trial were asymptomatic, 10% had AIDS and the CD4 cell counts ranged from 50 to 500. People in the trial received a single antiretroviral only (monotherapy) in the form of either D4T (40mg twice a day) or AZT (200mg three times a day). The interim results have shown that D4T improves immunological markers in people who have already been using AZT. In the group receiving D4T, there were improvements in CD4 counts, p24 antigen levels and viral load measurements as taken from human cells (PBMC). Also, weight gain was seen in the D4T treated group that was sustained for 80 weeks. All of the above markers declined in the AZT treated group of people. Quality-of-life measurements were significantly higher in the D4T group than the AZT group. The presenter of the report did, however, point out that these results need to be confirmed by clinical outcomes to see what real effect the D4T is having against HIV, and whether the improvement seen in the immunological markers will translate into a delay in HIV disease progression. In another session at ICAAC Bristol-Myers Squibb presented information about a trial with 41 retroviral naive patients (people who had never taken AZT, ddI, ddC or D4T) and 108 patients who had previously taken AZT for an average of approximately 69 weeks. When given D4T, the people who had never taken AZT before had a larger increase in CD4 cells than those who had taken AZT previously. The information from this trial was compared with the ACTG116A trial (AZT vs ddI). This showed that people who had never taken a nucleoside analogue before and then who took AZT had an increase in their CD4 cells for approximately 24 weeks, but people who took D4T as their first nucleoside analogue had an increase in their CD4 cells which remained above baseline for 48 weeks. In general, D4T is showing itself to be a more potent nucleoside analogue than AZT, but it is still early days, and the only way to really show any differences will be in the clinical outcomes of these groups of people as they are followed over time. AIDS Weekly, October 31, 1994 >Merke Protease Inhibitor (L-735,524) Results Reported at ICAAC By Alan Strum Two phase I clinical trial results were reported at ICAAC involving the monotherapy use of the Merke protease inhibitor L-735,524. In all, 16 people participated in the trials with a median CD4 cell count of 71. People received a total of 2.4 grams a day of the drug for 24 weeks. All participants were p24 antigen positive and had a 2 week AZT washout period before the trial started. Results showed a sustained 90% reduction in p24 antigen, a median body weight gain from 72kg to 81kg by the 24th week, and a median increase in CD4 cells of 77. Two people withdrew from the trial due to drug related toxicity, causing reversible problems with the liver. HIV RNA (viral measurements) levels were reduced by one log for the first 2 weeks, but then rebounded as viral resistance to the drug occurred. By the 24th week only 5 of the 14 remaining participants still showed the virus to be susceptible to the drug. AIDS Weekly, October 31 1994. >Side effects of ddC (Zalcitabine, Hivid). By Ian McKnight-Smith Last year Roche, the manufacturers of ddC, reported that the drug caused thymic lymphomas (a form of cancer) in mice when given at very high doses. Furthermore in one human trial, people who received ddC or a combination of ddC and AZT were more likely to develop this kind of cancer than were the people who were receiving AZT alone. However this effect may be just a fluke as there were no cases of lymphoma reported in the AZT alone group, even though it is an AIDS related Illness. Two studies that were reported at the International Conference on AIDS in Yokohama looked at this issue. The first study confirmed that ddC does indeed cause cancer in mice. Further the effects seen were directly related to the doses of the drug given, as well as how long ddC had been given for. In this study the mice developed lymphomas after 3 months of treatment at the very high dose of 1000 mg/kg/day. They also developed cancer when they were given a lower dose of 500 mg/kg/day over a longer period of time (4-6 months), It should be stated however that even in the latter case the dose of 500 mg/kg/day is still an extremely high dose and is about 16,000 times higher than the average dose used in humans to treat HIV. A further study conducted at the University of Colorado in the United States, looked to see if the tests that have been conducted in mice are a real guide to what may be happening when people with HIV take the drug.They reviewed previous studies that have suggested that mice have a different body metabolism to that seen in humans, and may therefore convert ddC to a cancer causing substance while humans do not have the same metabolic process. Another suggestion is that mice are more commonly infected with the viruses that cause cancer than is the case in humans. In this study, ddC seemed to cause cancers in mice by suppressing cells from which blood cells are derived. As ddC did not seem to suppress these cells in humans, the researchers suggest that the mouse studies are not a good indicator of ddC's likely ability to cause cancer in humans. A study in San Francisco confirmed that mouth ulcers are indeed more likely in people who are taking ddC than those taking the other nucleoside analogues such as ddI or AZT. In the sample 29% of those taking ddC developed mouth ulcers while only 15% of those taking AZT or ddI. >GEM 91 Phase I clinical trial results look good. By Ian McKnight-Smith At the recent Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in Orlando Florida, Hybridon announced that they will commence phase IB/II clinical trials with their antisense compound called GEM 91. (see October issue of HIV Herald for further information). The decision to expand research with this compound has been due to the favourable results of the phase I clinical work which was reported by Dr Ruiwen Zhang and Robert Diasio from Alabama. "This trial conducted at the University of Alabama, demonstrated that GEM 91 was well tolerated by all patients, which confirms the results of the earlier phase Ia study." In the phase Ia study a single dose of Gem 91 had been given to 30 HIV positive people with no clinically significant side effects being reported. "Secondly the latest study, the trial demonstrated remarkably reproducible pharmacokinetics which was helpful as we plan for multiple dose trials" said Dr Diasio. Also at ICAAC Professor Daniel Sereni reported their Phase Ia study results that were conducted in France. Sereni reported on the first 24 people treated with doses of up to 1 mg/kg of Gem 91. In a follow up study, the group have been given a single dose infusion of Gem 91 at escalating levels up to 2 mg/kg. No clinically significant intolerance was observed and the blood levels were in the right ranges to inhibit HIV activity. This study will continue to higher doses. Separately, Drs Groopman and Byrn, have demonstrated that resistance did not develop in the test tube against Gem 91 over a six month test period, whereas in a parallel controlled experiment significant resistance developed against AZT. Also, in another experiment Gem 91 was demonstrated to inhibit HIV isolates that had been drawn from people with HIV, and were resistant to AZT and ddI. The relative absence of resistance to Gem 91 may be related to the drugs mechanism of action, which is a genetic based therapeutic approach. So while much of this work is in the test tube or in very early use in people with HIV, the results look promising. It will be important to monitor closely the phase II work with the view of starting trials with this agent in Australia Ä if and when GEM 91 shows that it is effective against HIV in the body. OPPORTUNISTIC ILLNESSES >CLARITHROMYCIN AS PROPHYLAXIS AGAINST MAC By Ian McKnight-Smith The results of a recent study using clarithromycin as a single drug prevention (prophylaxis) against MAC (mycobacterium avium complex) were presented at the recent Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) held in Orlando Florida. This has sparked a considerable amount of discussion as to whether this drug should be made available as routine prevention of this illness in people with CD4 counts below 100. The study compared clarithromycin at a dose of 500 mg twice daily to a placebo control group as a prophylaxis against MAC. The study had 684 participants and all had less than 100 CD4 cells. They were randomised to receive either clarithromycin alone (N=343) or to receive a placebo (n=341). Participants who were randomised to receive the clarithromycin had a significantly lower incidence of MAC when compared to the placebo group (not really very surprising really, something being better than nothing). However there were 15 cases of MAC (4.5%) in the treated arm as compared to 42 cases (12.5%) in the placebo group. There were also significantly fewer deaths in the clarithromycin treated group N=74 [22%] as compared to 98 [29%] in the placebo group. If we look at the numbers of side effects reported there were more cases of nausea and taste distortion while on clarithromycin, while as would be expected, there were higher levels of fever in the placebo group. There was a 68% reduction in the risk of developing MAC on clarithromycin as compared to placebo, which is clearly a significant benefit and on its own would indeed suggest that this treatment was effective and should be considered for routine prophylaxis in this group of people. However 9 of the 15 participants (60%) that developed MAC while being treated with clarithromycin became resistant to the drug while all of the participants on the placebo arm who developed MAC remained sensitive to clarithromycin. This means that those 9 participants would receive no benefit if they use clarithromycin to treat an outbreak of the symptoms of the illness, and there is also a strong likelihood that those people will also not receive any benefit from azithromycin as there is nearly always rapid cross resistance between these two closely related drugs. Clarithromycin and azithromycin are major components of the first line treatment of MAC if and when symptoms of the illness develop. So if indeed the treatment were to be made available as a routine prophylaxis against MAC, then it is likely that resistance will develop to both of these drugs in a high proportion of the treated community and thus this will result in a situation where clinicians will lose two key treatments for this illness and thereby limit the options that are available to them. In contrast however results look far more encouraging with the use of rifabutin as prophylaxis since it appears to have similar efficacy in terms of preventing the illness but appears also to have a much lower incidence of resistant isolates developing. Indeed this drug has been approved by the FDA in the USA, and by ADEC in Australia, as prophylaxis against MAC. The problem at this time is that we are still waiting for reimbursement for this product, which is expensive. A study comparing clarithromycin versus rifabutin and a combination of the two drugs is ongoing. It is anticipated that there will be some presentation of progress results early next year. A combination of the two treatments may make more sense, since it would be hoped that the treatments would be more effective than if used alone, and the presence of two treatments would also make the development of MAC resistance even less likely. >Why do people with HIV develop an allergic reaction to co-trimoxazole? By Ian McKnight-Smith adapted from an article by Edward King at the National AIDS Manual in the U.K. Several suggestions have been put forward as to why people who are HIV positive are more likely to develop an allergic reaction when using co-trimoxazole (Bactrim/Septrin/Resprim) than people who have not been exposed to the virus or even in other people who have unrelated immunodeficiency problems. This drug is in fact made up of two separate drugs, trimethoprim (TMP) and sulphamethoxazole (SMX). It is widely accepted that the drug's allergic side effects are caused by the SMX component rather than the TMP, The reason for using the combination of the two drugs is that they work at slightly different points in the life cycle of the bacteria and their combined effects are greater than would be predicted from simply using each of the drugs individually. This is called a synergistic effect. Sulphamethoxazole is much more effective than trimethoprim against the bacteria that can cause diseases such as PCP (pneumocystis carinii pneumonia). In the case of other gut, urinary,and respiratory infections TMP alone may be just as effective but causes less side effects than the co-trimoxazole combination, but TMP alone has not been tested against PCP alone. In animal studies, TMP alone was unable to prevent PCP infection whereas the combination of TMP and SMX was effective. The side effects of SMX appear not to be caused by the drug in the form in which it is swallowed, but by a substance called a metabolite into which SMX is converted once it is in the blood stream. Inherited (genetic) differences may be one factor that causes some people to produce this metabolite more effectively than others, and this may explain why some people are more prone to developing side effects than others, Indeed, side effects from co-trimoxazole seem to be rarer among certain racial groups in particular African, Haitian and black Americans with AIDS than among caucasians. The expression of this inherited difference may also be more common in HIV positive people with more advanced stages of the illness. This theory may explain not only why co-trimoxazole causes side effects, but also why the side effects are more common in people with HIV. The toxic effects of the metabolite formed from SMX is usually cleared from the body by an important immune substance called glutathione. It is well recognised that glutathione levels are unusually low in people with HIV, and therefore this may then in turn allow an unusual build up of the toxic metabolite in the blood and hence cause the symptoms of the side effects. It may be possible to increase the levels of glutathione by taking the drug NAC, A trial to test whether NAC and co-trimoxazole reduces the incidence of side effects to the latter drug are currently being conducted in Canada. Other approaches would be to try to inhibit the production of the metabolite or to help the body remove it from the circulation more efficiently. However, It is probably worth taking some action to minimise the side effects that are experienced since co-trimoxazole has been proven to be such an effective treatment and prevention against PCP. It also provides a substantial protection against toxoplasmosis an illness of the brain and central nervous system. It is true that as many as 3 out of 10 people with HIV develop an allergy to co- trimoxazole. These reactions are characterised by rashes, fevers and a general feeling that you have 'the flu'. In many cases these effects are so serious that they have to stop the treatment. In some cases continued treatment would be life threatening. However, a number of centres around the world have developed what is called desensitisation protocols. That is to say, a method by which they can enable people to take the drugs that they would otherwise be allergic to. The way this works is to start by giving people minute doses of co-trimoxazole (see table 1) and then very slowly increase the doses of the drug so that on the fifth day they are then able to take the complete dose as is normally found in a standard double dose (DS) tablet. The success rate is high with reports of greater than 80% of people being able to take the normal dose without any side effects. It is also true that if the procedure is not successful on the first attempt some people will have success on a second or third round of doses. There are some reports that the benefits tend to wear off. In one report where 6 out of 8 people were successfully desensitised to co-trimoxazole, a proportion of these people had not ended up on the drug for very long. A few months on into treatment they have developed a 'grumbling skin' reaction or a low grade fever indicating a continuing but low level allergic reaction. In some of these cases even further on, they experienced the return of a skin rash. In most cases this will then mean the cessation of the treatment. However many would consider that any period of protection against these bacterial infections is a worthwhile exercise, and the numbers of people who are able to remain on longer term treatment after desensitisation is a significant number. Table I Co-trimoxazole desensitisation protocol As per St. Vincents Hospital Sydney Dose Volume Route of admin: Oral DAY 1 (use 100 microgram/mL suspension) 10 micrograms 0.1 mL 20 micrograms 0.2 mL 30 micrograms 0.3 mL 40 micrograms 0.4 mL 60 micrograms 0.6 mL 80 micrograms 0.8 mL 100 micrograms 1.0 mL 200 micrograms 2.0 mL DAY 2 300 micrograms 3.0 mL 500 micrograms 5.0 mL 600 micrograms 6.0 mL 750 micrograms 7.5 mL 1 milligram 10.0 mL 2 milligrams 20.0 mL (use 10 mg/mL suspension) 4 milligrams 0.4 mL 8 milligrams 0.8 mL DAY 3 15 milligrams 1.5 mL 30 milligrams 3.0 mL 50 milligrams 5.0 mL 100 milligrams 10.0 mL 200 milligrams 20.0 mL 400 milligrams 1/2 a DS tablet *800 milligrams 1 whole DS tablet DAY 4 1 double strength tablet taken 4 times per day DAY 5 2 double strength tablets taken 4 times per day or according to the persons weight for treatment of PCP *If prophylaxis only required omit 800 mg dose on day 3 and commence prophylaxis dose on day 4. GENE THERAPY >CD8 cells coded with a marker and a suicide gene. By Alan Strum The Fred Hutchins Cancer Research Centre, in Seattle Washington (USA), released some preliminary information about a gene therapy trial at the recent ICAAC meeting. The trial is enrolling 15 people to have some CD8 cytotoxic cells removed. Once removed, the cells are inserted with 2 genes which have a specific purpose. One gene will enable the researchers to track where the cells go to within the body when they are put back in (ie where will the cells go to fight against HIV). The other gene is what is being called a "suicide gene". This suicide gene is a safe guard to ensure that the cells can be destroyed if they cause an undesired adverse effect to the body when they are put back in. The way in which the cells are destroyed is to introduce a substance to the body which triggers the gene to kill the cell that it is in. In this case the substance to trigger the cell death is ganciclovir. The CD8 cells are also to be activated against a part of HIV and are to be grown in cell cultures to greatly increase in cell numbers (propigate). This way lots of new CD8 cytotoxic cells can be placed into the body that will hopefully kill or inhibit cells that are infected with HIV. 4 separate infusions with the altered cells are planned for the participants. So far 6 people have had their own CD8 cells reintroduced to their bodies with one person reporting a low grade fever, two people reported muscle pains and night sweats, and 3 people have had no apparent side effects from their altered CD8 cells. Once the trial has been completed, 3 of the 15 trial participants will be given ganciclovir to see if their altered cells will suicide. Other areas of development for the insertion of genes into CD8 cells is introduce genes that will allow the CD8 cells to function without the need for the presence of CD4 cells. AIDS Weekly, October 24 1994. COMPLEMENTARY THERAPIES >SOME SUGGESTED COMPLEMENTARY TREATMENTS By Ian McKnight - Smith At the recent Positive Living Conference, held in Sydney a session was devoted to the use of complementary treatments and an interesting paper was given by Peter De Ruyter, a prominent HIV complementary therapist. His discussion suggested that there is much that can be done both in terms of allopathic (western) medicine and the various disciplines in complementary therapy. He strongly indicated that neither should be exclusive of the other, and that clinicians in both schools of therapy should get a better understanding of each others approach. He also indicated that there are no "magic bullet" treatments in HIV and that it is a concerted effort to retain the highest levels of "life force" for the longest periods of time. To achieve this, his approach is reduce as many of the possible events that will drain life forces. Some these include, smoking or taking recreational drugs and of course this includes tobacco, alcohol and marijuana, while others would include late nights, stress, poor diet and so on. He also suggested that the use of some of the western medicines may be toxic or have side effects and they then in turn will drain the life force levels. However, in his opinion probably one of the most significant and most overlooked factors is the mental approach to the condition. That is to say the likelihood that a person with HIV who feels that they will get sick, will indeed get sick. On the other hand the person who mentally conditions themself to remain well, is far more likely to do so and for long periods of time. There are no quick fix remedies and he suggests that anyone who is considering the addition of natural or complementary treatments to their own health care should first consult an appropriate therapist for advice on your individual needs. Peter did suggest however there are a number of natural treatments that can assist and provide "first aid" against a number of conditions. We have included a list of his suggestions as a guide to some of the conditions often faced by people with HIV and AIDS. ANOREXIA (excessive weight loss) Swedish Bitters The dose is between 2-5 ml diluted in water and taken 1/2 an hour before food. Bitter Herbs such as Gentian and Yarrow Both of these are available from health food stores NAUSEA Ginger As a tincture or made as a tea from the fresh root; 1 teaspoon of finely sliced root per cup of boiling water Swedish Bitters The dose is the same as for anorexia NIGHTS SWEATS Sage Tea 1 teaspoon dried herb per cup of boiling water and allow to stand for several hours. Dose 1 cup 2-3 times daily. Homeopathic Reckeweg R32 (available from practitioners or from Newtons Pharmacy 119 York Street Sydney ..Ph 02 267 7889). Place 10-15 drops under the tongue 3-5 times daily or as needed during the night. MOUTH ULCERS Vitamin B5 100-200 mg / day Zinc This can be obtained by taking "control acidophilus" 1 capsule three times per day. Beta carotene 50-100,000 international units per day for several weeks and then decrease the dose. Acidophilus FATIGUE Coenzyme Q10 Up to 4 capsules taken 3 times a day DMG 2ml taken twice a day. Spirulina 3 capsules taken 2-3 times per day. Herbal Tonics such as Bitter Melon tincture SHINGLES AND HERPES Homeopathic Reckeweg R68 10-15 drops under the tongue from 3 times daily up to every hour depending on the severity of the outbreak.(available from practitioners or from Newtons Pharmacy 119 York Street Sydney ..Ph 02 267 7889). L-lysine 500 mg four times a day taken on an empty stomach. I.M.I. B12 injection 1 mg per day (available from your chemist). Hypericum 2ml taken three times per day (available from practitioners). Leek juice apply the juice of the vegetable to the sores to help alleviate the pain. Cut out all chocolate and nuts since they are high in arginine which feeds the virus. Lecithin 1-2 gram capsules taken three times per day Homeopathic "Zincum met.30" 5 drops under the tongue twice a day to minimise the post herpetic neuralgia. This is available from practitioners. DIGESTIVE DISORDERS AND MALABSORPTION Swedish Bitters This stimulates the gastric/pancreatic and liver secretions The dose is between 2-5 ml diluted in water and taken 1/2 an hour before food. Bitter Herbs such as Gentian and Yarrow Both of these are available from health food stores Acidophilus But have your practitioner check for and treat bowel infections/ecological imbalances. Beta carotene 20,000 i.u,/day "Control acidiphilus" 1 capsule taken 3 times per day. DIARRHOEA Herbal Composition Powder (Nupro) 3 capsules taken 3 times per day Acidophilus Garlic Although in some cases this may not be appropriate. Gastrolyte Available from most chemists Hydrochloric acid supplements These can be very effective but must always be taken with food! Homeopathic Reckeweg R4 (available from practitioners or from Newtons Pharmacy 119 York Street Sydney ..Ph 02 267 7889). 10-15 drops 3 times per day or every half an hour if uncontrolled. Slippery Elm Powder. 1 tablespoon in -white rice 1/2 cup -1/2 grated apple allowed to go brown -acidophilus, 1 teaspoon -Probioplex, 1 tablespoon -Gastrolyte mixed into to make a porridge. -Cinnamon or nutmeg to taste. This can be eaten as often as desired, and helps supply some calories/nutrients/electrolytes as well as often settling the diarrhoea. ORAL HAIRY LEUKOPLAKIA Beta carotene 100,000 i.u per day + folate 3-5mg per day. This treatment should be taken under the supervision of your practitioner. Propolis lozenges