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NOTES FROM THE UNDERGROUND
The PWA Health Group Newsletter
"Access to Information Precedes Access to Treatment"
September 1998 Issue 37

Table of Contents

HYDROXYUREA-EVER MORE FASCINATING!
by Tim Horn

The AIDS/HIV treatment pipeline is simply full of surprises. Hydroxyurea, a relatively powerful experimental treatment for HIV, has managed to steal the spotlight from the ever-mighty protease inhibitors and continues to baffle even the most jaded researchers and treatment advocates. For starters, hydroxyurea isn't even an antiviral; it is an anti-cancer drug-approved as a treatment for leukemia and advanced ovarian cancer-and has been on the market for more than thirty years.

Numerous test tube studies have shown that hydroxyurea is capable of slowing down, maybe even stopping HIV replication in virtually all immune system cells and tissues; a feat beyond that of many antiretrovirals approved to date. They also show that it does not cause resistance while somehow increasing the activity of some antiviral drugs against drug-resistant strains of the virus.

Finally, over the past year, one group of researchers studying hydroxyurea has claimed to have achieved sustained undetectable viral loads in two newly-infected people for one year after all antiviral drugs were stopped. Adding an interesting twist is the fact that Bristol Myers Squibb, the manufacturer of hydroxyurea, no longer holds the patent to the drug, allowing competing manufacturers to produce generic, low-cost versions of the same compound.

Claims about hydroxyurea's potential benefits are not new to the HIV/AIDS community. Hydroxyurea made its debut in 1993 at the IX International AIDS Conference in Berlin, when Dr. Robert Gallo, then with the National Cancer Institute (NCI), presented early test tube results involving hydroxyurea. Gallo showed that the drug had potential antiviral activity, not by manipulating parts of HIV like other antiviral drugs, but rather by altering parts of the cell which HIV targets instead.

Hydroxyurea alters the cellular enzyme ribonucleotide reductase, a protein needed by the virus so that it can transcribe its RNA into DNA inside the cell. The body uses ribonucleotide reductase to produce proteins called dNTPs which are normally used as building blocks to make DNA, the genetic material of cells. In HIV-infected cells, the dNTPs are used by HIV's reverse transcriptase (RT) enzyme to transcribe its RNA into DNA. The viral DNA can then take over the cell's nucleus, turning it into a virtual HIV factory. Without ribonucleotide reductase, the virus cannot successfully take over the cell.

Hydroxyurea and Drug Resistance
Because hydroxyurea directly interferes with the functioning of the targeted cell and has no contact with the virus, the chances of developing resistance are much lower than it would be with most or all antiviral drugs currently approved. Those drugs -- protease inhibitors, nucleoside analogues, etc. -- directly interfere with how the virus works. Because the virus changes its structure (mutates) rather quickly, a drug or combination of drugs that directly targets HIV may become weak and unable to halt HIV production. While cells are capable of mutating and becoming resistant to the onslaught of drug therapy, they often do so at a much slower rate than viruses.

Towards the end of 1994, a paper published in Science made some startling claims regarding hydroxyurea. The paper, prepared by Dr. Franco Lori and NCI's Robert Gallo, reported that hydroxyurea surpassed the antiviral activity of all antivirals, given its capability of halting HIV replication in virtually all immune system cells and tissues, including the brain.

Its ability to penetrate the brain means that hydroxyurea has the potential to treat or prevent neurological diseases directly caused by HIV, such as HIV encephalopathy. Hydroxyurea also penetrates the lymph tissues where the majority of HIV in the body is thought to be. Studies have shown that most drugs currently approved do not easily enter these major reservoirs of HIV.

Side Effects and Toxicities
The blood levels of hydroxyurea needed to slow or stop HIV are approximately 50 times lower than those required to treat leukemia and other forms of cancer. Like most cancer drugs, hydroxyurea can reduce bone marrow production of white blood cells, red blood cells, and platelets. While safety data from hydroxyurea studies involving people with HIV/AIDS seem to suggest that the standard research dose-500 mg twice daily-does not appear to be associated with any major side effects, it's possible that hyroxyurea may cause low red blood cells (anemia), low white blood cells (leukopenia), and low platelets (thrombocytopenia). This may be especially true if you take hydroxyurea with other drugs that cause these problems, such as AZT and other cancer drugs.

HIV Studies
In recent years, hydroxyurea has been put to the test, most often in combination with ddI (Videx) and sometimes d4T (Zerit)-a highly suspect combination of three Bristol Myers-Squibb drugs-in a number of small clinical trials. According to Dr. Lori, hydroxyurea boosts ddI's strength 20 times without causing additional side effects. In test tube studies, the combination was able to bring viral replication to a virtual stand still (99.9% decrease in viral activity). Moreover, Lori has found that in both test tube and clinical studies, hydroxyurea allows ddI to work even against strains of HIV that have developed resistance to ddI. While the combination of ddI and hydroxyurea does not prevent the emergence of mutations that cause ddI resistance, resistant mutants still remain sensitive to standard doses of ddI in the presence of hydroxyurea. The reason for this is not entirely understood and is still being investigated by Lori and other researchers. There has been a slew of small and medium sized clinical trials of hydroxyurea and ddI.

Trials have involved both previously untreated (naive) and treatment-experienced patients and have yielded fairly consistent results. The majority of patients in clinical trials were able to achieve at least a 1.5 log reduction in viral load, regardless of their prior drug experience. Not surprisingly, undetectable viral loads were most commonly reported in people with low viral loads (usually less than 10,000) and little or no drug experience. In one particular study of ddI/d4T hydroxyurea, treatment-experienced people had viral-load decreases of 30- to 300-fold.

Apparently, the proof that hydroxyurea is effective is not in its ability to elevate T-cell counts. While some studies have demonstrated an increase of more than 100 T-cells in people taking hydroxyurea/ddI therapy, this was most often the case in people who had high T-cell counts (greater than 450 cells) to start with. Because hydroxyurea can suppress the bone marrow's ability to produce new white blood cells, it is not surprising that its use did not result in substantial T-cell increases.

Data from one particular trial of hydroxyurea and ddI, reported by Dr. Jorge Vila in the British medical journal Lancet, caused quite a media frenzy. The study involved two newly-infected people who took ddI and hydroxyurea (standard doses of both). Patient A had been infected for three months and patient B had been infected for twelve months. Both volunteers had very low viral loads; patient A had 676 copies and patient B had 1,120 copies. After a year on this combination, both had undetectable viral loads and only one, patient B, was found to have a traceable amount of viral DNA in his lymph node sample.

Both volunteers agreed to stop their antiviral therapy at the end of the first year. After one year off therapy, both their blood and lymph nodes were re-checked for viral load. The researchers could not detect virus in either of their blood samples but were able to detect viral DNA, although extremely low levels, in their lymph nodes. Two years after stopping their antiretroviral treatment the volunteers still had no viral rebound.

Proviral DNA was still present, although at very low levels. As outlined above, one explanation for the continued absence of viral load going up in these people could be that this combination works in resting cells-such as non-activated lymphocytes (including T-cells, monocytes, and macrophages)-which are thought to harbor a significant amount of virus, and are virtually untouched by the other antivirals.

However, it is important to understand the limitations of this study. Data from newly infected individuals-whether they involve hydroxyurea, protease inhibitors, or any possible combination of therapies-does not necessarily apply to all people infected with HIV. Hydroxyurea, like all anti-HIV therapies, needs more carefull study. Studies should investigate every possible characteristic of HIV infection: heavy to moderate treatment experience, drug naive as well as asymptomatic and symptomatic people (men, women and children of all ages, ethnic origin and sexual orientation) with HIV.

The possibilities of hydroxyurea as a treatment option are, quite possibly, endless. Perhaps hydroxyurea's prolonged anti-HIV activity, in the absence of active drug therapy, will require only periodic bursts of treatment, rather than a continuous dosing schedule, minimizing toxicity. This carries extraordinary possibilities for further reducing perinatal transmission rates, especially in geographic locations with limited antiretroviral access. Studies to assess the potential benefits of hydroxyurea for severely immune-compromised, antiretoviral-experienced people with low T-cells must be initiated immediately.

Hydroxyurea continues to be studied in various clinical trials-most of which are too small to answer significant questions-in the United States and Europe, including an ACTG trial (ACTG 307), and an AmFAR sponsored trial, fully enrolled, should have results shortly.

How it's given
By mouth. One tablet in the morning and one in the evening (500 mg twice a day). The capsules should be swallowed whole with plenty of water.

Where it's available
Hydroxyurea is available from most pharmacies, with a prescription. Because hydroxyurea is not specifically approved for the treatment of HIV, HIV-infected folks who rely on ADAP don't stand a good chance of getting access to the drug. Because Bristol Myers-Squibb no longer holds the patent or exclusive marketing rights, it is entirely possible that hydroxyurea may never be approved by the FDA as an effective treatment for HIV.

Possible side effects
Like many anti-cancer drugs, hydroxyurea can alter the body's ability to produce new white blood cells and red blood cells. This can result in fatigue and anemia (due to low red blood cell production); risk of bruising or bleeding (due to low platelet production), and lymphopenia (reduced lymphocyte production). This effect is usually mild, especially with the low dose being studied for HIV.

NEW DATA!
Numerous studies of hydroxyurea have shown how effective it can be in terms of drastically reducing viral load. But what about the immune system? Because hydroxyurea does not appear to increase T-cell counts and may even lower them, this may not be welcome news to people who already have low T-cell counts.

Does hydroxyurea offer any benefits to the immune system?
In recent months, many researchers have been scrambling to find out how strong the immune system really becomes after starting antiviral therapy. After all, someone with 100 T-cells who experiences a 200 T-cell increase after starting antiviral therapy may not be out of the danger zone just yet; we still don't know how healthy these new T-cells really are. T-cells can be broken down into two different groups: naive T-cells and memory T-cells.

Naive T-cells are new T-cells produced by the body that can respond to any disease-causing organism it encounters. Memory T-cells, on the other hand, are needed to respond to organisms that have invaded the body before; it's much easier for the immune system to respond to the presence of a familiar organism than to a new, unfamiliar one. Infections such as tuberculosis, PCP, and CMV are all kept in check by memory T-cells.

At a conference this past winter in Chicago, much new data from studies of hydroxyurea demonstrated that the drug does have an effect on both of these types of T-cells. Naive T-cells were increased quite a bit, 140% in people taking hydroxyurea. Overall, memory T-cells increased but at a much slower rate than naive T-cells. These results are similar to those from many other studies involving other antiviral drugs. The bottom line? Even if you experience a massive T-cell increase, it may take awhile, possibly a year or more, to ensure that these T-cells are capable of doing the job they're supposed to do.

THALIDOMID-THE STORY GOES ON...
by James Learned

In mid-July, the FDA approved thalidomide as a treatment for leprosy (Hansen's disease) with the brand name, THALOMID. So begins another chapter in the complicated history of a drug with enormous clinical potential as well as dangerous possible side effects. Working with the FDA, Celgene Corporation (one of the drug's manufacturers) has developed a distribution program modeled on the program we created in mid-1995.

It was at that time that the PWA Health Group first imported the drug for PWAs suffering from aphthous ulcers (painful sores in the mouth, throat, vagina or rectum) and/or wasting (unexplained weight loss). Our rigorous standards and requirements (a 21 page booklet of necessary information with informed consent signed, supply limited to 10 days per prescription, a new prescription required with refill and one-on-one counseling session) established the blueprint for Celgene and the FDA to open compassionate use access to the drug for AIDS indications.

THALOMID's approval requires doctors and pharmacies to register with the FDA in order to provide the drug to patients. The program will help educate doctors, pharmacists and patients about the drug's pros and cons, but the intention is also to restrict and control access as much as possible. Off-label use will definitely occur, probably a lot. In other words, doctors will prescribe it to treat conditions other than leprosy, conditions for which it has shown some promising results-AIDS-related wasting, aphthous ulcers, kaposi's sarcoma, microsporidiosis, cancer and lupus. The drug will be dispensed before your final approval is granted and it will be discontinued if your reason for use is disapproved by the FDA.

For information about how to register to prescribe THALOMID, your doctor and pharmacist should call Celgene: (888) 423-5436. Informed consent will be required of anyone before they receive the drug. Women of "child bearing age" will need proof that they're not pregnant, and each prescription, which will be limited to 28 days worth of drug, must be filled within seven days or it expires. Celgene is aiming for Oct. 1. but probably won't have THALOMID on pharmacy shelves until mid-October, 1998. If you have questions about Celgene's program please call Dr. Ken Resztak, Director of Medical Services at Celgene Corporation, (732) 805-4083.

THALOMIDE's approval is a victory for PWAs and others who need access to the drug. But the victory carries enormous responsibility. The birth defects caused by thalidomide forty years ago weigh heavily on all considerations of its use. Other possible serious side-effects include peripheral neuropathy, neutropenia (fewer white blood cells that help fight infections) and heavy sedation. Educational pamphlets, informed consent, and restricted access have been useful tools in the Health Group's program, and hopefully, will be enough to keep history from repeating itself. As THALOMID becomes more widely available to people with life-threatening conditions, including those that are HIV-related, we can only hope that these tools will remain successful.

The approval of thalidomide as THALOMID does not mean that clinical trials of thalidomide are now closed. Here are phone numbers to call if you or your doctor are interested in other ways to get the drug:

  1. Pediatric Pharmaceuticals: (732) 603-7708. FAX (732) 632-2522
    Doctors need to get an IND from the FDA (see #5 below). Drug is shipped in bottles of 200 tablets (100mg) for $210, prepaid with a check. Cost includes $10 shipping.
  2. Andrulis: (301) 419-2400
    Doctors need to get an IND from the FDA (see #5 below). This program is HIV friendly and they have the ability to help those who can't pay. Drug is shipped in bottles of 100 tablets (100 mg) for $309.
  3. Clinical Trials Info: (800) TRIALS-A (AIDS trials)
    (800) TRIALS-C (Cancer trials)
  4. The Network: (212) 260-8868 or (800) 734-7104.
    The Network helps you locate experimental treatments and clinical trials information.

Sometimes things aren't as easy as they would seem. If you run into trouble with any of these programs please call us or have your doctor call us here at the PWA Health Group, (212) 255-0520. We will do everything in our power to help you get the treatment you need.

One From Column A and Two From Column B
by Mark Niedzolkowski

Column AColumn B
Alternative TherapyTraditional Therapy
Complementary TherapySupplemental Therapy
Holistic TherapyNatural Therapy
Natural TherapyHolistic Therapy
Supplemental TherapyComplementary Therapy
Traditional TherapyAlternative Therapy

Not a week goes by that we at the PWA Health Group don't get at least one request from someone for information on alternative, complementary, holistic, natural, supplemental or traditional therapies. When the question comes up during a one-on-one conversation it's easier to scope out just exactly what's being requested. However, when the question pops up in a piece of mail , it's harder to figure out.

To some, alternative therapy is a huge umbrella term which covers all the others, plus vitamin therapy and even the "hands on" healing arts (massage, reiki, shiatsu, et al). To some, an alternative therapy is simply less toxic or non-toxic substance which can substitute for the traditional therapies they are on or thinking of starting. There are many interpretations, people are very creative.

ALTERNATIVE: "employing or following non-traditional or unconventional ideas, methods, etc.; existing outside the establishment: an alternative newspaper; alternative lifestyles; alternative therapies."1

The most common misconception about alternative therapies is that there really are alternative therapies out there which will work as well as traditional western medicines that you are trying to void. Somewhere along the way, in our search for a cure for AIDS, we got it in our heads that there has to be an alternative cure as well. The problem is that almost all of the information about these "phantom cures" is word of mouth and rumor, not to mention the occasional salesperson.

Only after a sufficient number of people are trying something or talking about it do we see any real discussion of alternatives amongst the men and women who write and publish our newsletters and who we trust to decipher the technical information released by the scientific community. It is often possible to hear or read personal testimonials by people who have a strong belief that they have been helped by some alternative therapy; however, it is just as often impossible to find legitimate documented clinical trial results on these alternative therapies.

The real truth is that we are all different and what helps you might just kill me and vise/versa. Don't misunderstand. There are lots and lots of people who swear by their alternatives. They just don't have clinical data to back up their claims. When you are taking these "non-toxic" alternative therapies, you are experimenting on yourself (and there's nothing wrong with that), and therefore you are responsible for checking your blood work and determining that you are getting the results you desire.

Some examples of alternative therapies include: vitamin C drip, massage therapy, yoga, acupuncture, anti-oxidants and plasma pheresis. There are lots more, too many to mention them all here.

There are no federal agencies out there charged with watching out for our butts when we start to play around with alternatives. What we have are manufacturers self regulating with no unbiased independent agent verifying that what they say it is on the label is what it really is. We are truly on our own. Buy products from companies you trust. Don't be afraid to ask the manufacturer for proof of their claims. Pay attention to where your information comes from, and always be aware that the alternatives you're taking may produce adverse interactions with the traditional meds you're taking. Just because it's called an alternative doesn't automatically mean it's good for you.

With HIV/AIDS we have base line numbers as our markers to tell us if we are successful in our attempts to control viral replication and T-cell counts. Just because an alternative makes you feel better, doesn't mean it's having a beneficial effect on your viral load or T-cells. Conversely, it's important to remember that even if what you're taking isn't giving you the results you want in terms of your T-cells and viral load but it has improved the way you feel then maybe it's doing something good and you might want to keep taking it. There is value in feeling better.

COMPLEMENTARY: "to make additions to something, to provide something felt to be lacking or needed; it is often applied to putting together two things, each of which supplies what is lacking in the other, to make a complete whole."

"Oh, what a pretty pill. It goes so well with your outfit." No, that's not what I mean by complementary. What are some complementary therapies? An example would be grapefruit juice. Grapefruit juice was used as an addition to saquinavir because it provided what was lacking and made saquinavir more bio-available, increasing the amount of saquinavir in the blood to effective levels. Saquinavir needed a good shot in the arm and grapefruit juice was a useful complement.

Another example of complementary therapies is a bit more complicated. Anti-oxidants. If you decide to use them, you need to study how they react to each other. In other words, it is pretty common knowledge that anti-oxidants are good for us. In essence they are supposed to clean out the "rust" in our systems.

None of us want to have a rusty system. But, just like in any good clean up scenario, toxins can be released and these toxins can harm you. So, to avoid harm from toxins it is necessary to study how anti-oxidants work with and for each other.

Let's imagine you decide you want to take L-Glutamine Fuel. It is a good idea to add a few things to make sure that you receive all of the benefits you are seeking, without harm. The complements to L-Glutamine Fuel are vitamin C, vitamin E, NAC, Beta Carotene, Selenium, Garlic, Thioctic acid and exercise. I'm not saying that any or all of these things are bad for you if taken alone. What I'm trying to point out is that when they are put together, they complement each other. While each does its own job, it also cleans up the refuse left by the others.

If you want to be literal we can look at triple combinations of anti-viral drugs as complementary therapy. Each of the anti-virals when combined with the others adds something which the others lack or need. In other words, they complement each other.

HOLISTIC: "identifying with principles of holism in a system of therapeutics, especially one considered outside the mainstream of scientific medicine, as naturopathy or chiropractic, and usually involving nutritional measures."

When I first started working in AIDS, I thought that holistic meant natural-wrong! An holistic approach is one which is concerned with the principles of holism or, to put it into other words, it concerns not only our bodies needs but also our mind's needs as well as the needs of our spirit. It's a philosophy which addresses the needs of the whole being, not just the specifics of your diagnosis.

Take cancer, for example. If you were to take only the traditional western approach to treating cancer, you would simply concern yourself with your chemotherapy and nothing else.

Chemotherapies are designed to attack the cancer and only the cancer, while doing little or no damage to other parts of the body. Yes, it makes your hair fall out and it's hard to get a meal down much less keep it down and you generally feel like shit. And, your doctor will tell you that's a small price to pay for getting rid of the cancer, so grin and bear it.

Chemo is usually administered in a sterile medical environment where there is little concern for anything other than a swift and efficient infusion of the chemo. Little concern is shown for the many other things a patient of chemo can experience.

An holistic approach to the treatment of cancer might include chemo, but would also be concerned and provide support for emotional and spiritual needs of the patient - making it easier to face the responsibility of having to make hard choices. In other words holistic isn't a product or a tangible substance that you can actually take, it's a philosophy. You can't really think of an herb or a specific treatment as holistic in and of itself.

What might an holistic approach to treating HIV/AIDS look like? Many PWAs have more than one doctor, an infectious disease doc (traditional western MD), possibly a Chinese herbologist (traditional Chinese MD) and maybe an acupuncturist. They take advantage of at least one of the many healing arts (Reiki, Massage, Shiatsu, Rubenfeld synergy, etc.) on a weekly basis. They have incorporated a well thought out regimen of vitamins and supplements with whatever western meds they have chosen (or chosen not) to take.

Many people regularly work out at a gym or take an aerobics or yoga class every week. Some just go out dancin' every weekend. Many PWAs find that some form of individual mental health counseling or therapy coupled with at least one good support group on a weekly basis is an important component of an holistic approach.

Often PWAs find themselves on a spiritual quest which involves reading about or studying different religious philosophies. Some find spiritual peace in meditation, while others are helped by a new found religious verve. This addresses the needs of the whole person, body, mind and spirit, a real holistic approach. It's a mix and match philosophy-some people need to put a stronger emphasis on the spirit while others need to focus on their mind and body. You have to create your own recipe for success and can change it as you discover which things in your recipe work and which don't. One thing that everyone does who takes an holistic approach to treating themselves, is learn everything they can about their diagnosis.

NATURAL: "having undergone little or no processing and containing no chemical additives, a natural substance or a product made with such a substance."

Probably the most common mistake that people make is to assume that if it's natural, it's good for you. Mostly it's a problem of semantics - if you are in need of treatment and you have the choice between a synthetic or natural therapy, the natural choice may be easier on your system. But it may also work a good deal slower than the synthetic or processed therapy. Whether you go to a traditional western or Chinese doctor with a viral infection, if they know what they are doing, each will want to treat the viral infection. The treatment will be with an antibiotic. The difference will be in how long it takes to work and how the treatment will be administered.

A western prescription will be for 8 to 10 days of antibiotics (pills) and the Chinese prescription will be for several bags of herbs (twigs, leaves, seeds, bark, etc.) which will come with instructions for cooking and dosing in tea form over the next 21 days (some Chinese docs have standardized formulas which they have in pill orcapsule form. Personally, I prefer the tea).

The western medication is a substance which may have started out as a natural substance but has probably been processed in one way or another and may contain chemical additives, but it works fast.

The Chinese medication is all natural but takes for- ever. Sometimes it's good, real good, to feel better in a couple of days as opposed to a couple of weeks. An interesting thing to know about natural is that most of the poisons known to man are natural substances.

Sometimes when you are taking an holistic approach it is of value to you to take three weeks to get rid of a bug-the process of drinking the tea three times a day can be a kind of ritual which can play into a meditation schedule. In that case, the benefit to your spiritual process is of greater importance to you than the discomfort of the infection you're trying to get rid of. It's a matter of making a wise and educated choice.

SUPPLEMENTAL: "added to complete a thing, supply a deficiency, or reinforce or extend a whole, added to furnish what is lacking or missing."

Supplemental therapy is very close, almost interchangeable with complementary therapy. More often than not when we consider using supplementation it is because of a feared dietary deficiency. If your diet doesn't provide you with the RDA (recommended daily allowance) of vitamins and minerals, then it's important to change your diet or supplement with pills or potions of whatever it is that you are lackingMany people with wasting will supplement because their lack of appetite and inability to eat as much as they should will prevent them from getting the vitamins, minerals, nutrients, proteins, carbohydrates and fats necessary to maintain a healthy body weight. There are many different supplementary pills, powders, drinks and shakes out there. Each of these supplements is designed to meet the specific nutritional needs of the individual.

They each have high doses of the supplements required and they provide their dose in small, easy-to-ingest portions, which can add to a person's comfort.

TRADITIONAL: "a long-established or inherited way of thinking or acting, a continuing pattern of culture beliefs or practices, a customary or characteristic method or manner."

When we use the term traditional medicine, what we usually mean is western medicine. Sometimes we actually say "traditional western medicine." For those of us who have been raised in western society our largest comfort zone comes from trusting our primary physician. When we talk about our primary physician what we are talking about is a doctor who was traditionally trained in western medicine.

I personally use three doctors; one is a licensed physician who practices Chinese herbology, one is a licensed physician who practices acupuncture, and one is a licensed physician who practices traditional western medicine and is my primary physician.

Western medicine can be divided into three basic categories: diagnostic, surgical and pharmacological. All three categories deal with specific physical symptoms and their treatment. Traditional western medicine tends to be very clinical in its approach to diagnosis and treatment. Clinical means a controlled, fact based approach, no guesses.

The philosophy of western medicine places the highest emphasis on finding out what the problem is, fixing the problem and then returning the patient to as normal a life as is possible quickly. Traditional western medicine is much more about the specifics of the problem. It looks at the part of the body that is problematic without really considering the whole person. The approach to good health of traditional western medicine may not be complete, but it is extremely valuable.

We start our medical journey with an empty tool bag, we learn and are educated about what's going on in our bodies, and on our journey we discover a vast diversity of available treatment approaches. We begin to fill our tool bag with an assortment of different tools, each with a specific job, and we learn how and when to use these tools to our advantage. At the end of our journey, if we have used these tools well, we should be left with a sense of peace and tranquility, if not good health.

I think that the most complementary thing we can do for our good health is to take an holistic approach and find some good natural alternatives which we can use to supplement our traditional treatment regimen.

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UNITED AGAINST AIDS INTERNATIONAL (UAAI)
This committed group of humanitarians is attempting to provide the latest HIV/AIDS medications to developing countries. Without a modern health care system and the money to pay for expensive medications citizens infected with HIV/AIDS can't treat their illness. UAAI provides programs which raise the level of education and awareness in these countries. Through carefully monitored and professionally dispensed donations of medicine and medical supplies, which you or a loved one no longer need, you can help UAAI help others. Everything is needed, from antivirals to sterile gloves and bedpans-not to mention condoms.

If you can help with medicines, supplies, equipment or money we urge you to call Hugh Ward, Executive Director, UAAI (718)639-5696. You can also drop any of the aforementioned items off at the PWA Health Group, 150 W. 26th St., Ste.201 or call (212) 255-0520.

PWAHG VOLUNTEERS NEEDED
Are you concerned about people with HIV/AIDS? Would you like to contribute more than $$$ to AIDS? Do you have 4 free hours per week? If you answered yes to any of these questions you sound like the kind of person we're looking for. Call Mark at (212) 255-0520 and sign up for our ongoing volunteer training programs, including free treatment education training!!

WARNING! NORVIR (RITONAVIR) PROBLEMS WITH CAPSULE MANUFACTURING
Abbott has acknowledged a problem with the manufacture of its capsule formulation of Norvir. They have discovered an unexpected crystallization in the capsules which will affect how the drug dissolves. They have reassured us that this problem is new and does not affect the supplies already on pharmacy shelves. The bad news is that until this problem is resolved, everyone will be shifted to the liquid (elixir) formulation. The other bad news is that it tastes bad, really bad.

More bad news is that it must be kept unrefrigerated at temps of 68-77 degrees Fahrenheit (20 degrees Celsius). The baddest news-the liquid formulation is 40% alcohol, a problem if you're in recovery. Abbott does not know when the problem will be resolved, but assures us that there is plenty of liquid to go around. There's a Hotline set up to help with questions you have as well as a web site with relevant information.

The dosing of the liquid formulation is as follows:

NEW TRIAL STARTING
The U.S. National Institutes of Health (NIH) is starting a small trial to test a new kind of HIV vaccine in combination with standard antiviral therapy, to try to bring back HIV-specific immune responses in volunteers with relatively early HIV disease.

This trial is open to persons who currently have a T-cell count of over 500, and who either are on antiretroviral treatment already, or are willing to start. Volunteers must never have had a T-cell count under 300, unless the low count occurred during acute HIV infection. All medications will be paid for and the trial lasts 18 months.

Interest is growing rapidly for ways to restore HIV-specific immune responses. This trial will add information to the growing file of data at the NIH on immune restoration.

For more information about volunteering for this study, contact Tino Merced-Galindez, RN 800/772-5464 ext.562 or 301/496-8959, or merced@box-m.nih.gov, or Richard Little, MD 800/772-5464 ext.657, or rlittle@helix.nih.gov at the HIV and AIDS Malignancy Branch, National Cancer Institute.

POTENTIAL INTERACTIONS BETWEEN CHOLESTEROL LOWERING DRUGS AND PROTEASE INHIBITORS
It has been reported that some people on highly active antiretroviral combination therapy which include protease inhibitors are experiencing increases in their cholesterol levels. High cholesterol levels are associated with heart disease. Therefore, some doctors are treating increased cholesterol with cholesterol-lowering drugs. The most commonly prescribed and most effective drugs available to lower cholesterol levels are the "statins". There is little or no information about the interaction of these drugs with protease inhibitors, but both are processed by an important group of liver enzymes, CYP3A.

Although there's little or no information on using statins with protease inhibitors, the FDA has examined the differences in how these cholesterol-lowering drugs are processed in the body. Lovastatin (Mevacor) and simvastatin (Zocor) are very dependent on CYP3A. There is a greater chance of drug interactions if Mevacor or Zocor are used with protease inhibitors.

Atorvastatin (Lipitor) and cerivastatin (Baycol) are less dependent on CYP3A but there still is a chance of a drug interaction if either is used with a protease inhibitor. Fluvastatin (Lescol) and pravastatin (Pravachol) are not dependent on CYP3A and are probably safe when used with protease inhibitors. In June, the FDA amended Pravachol's label to address this drug's reduced potential to interact with CYP3A, decreasing the likelihood of drug interactions.

The risk of using the CYP3A-dependent statins, particularly Mevacor and Zocor, with protease inhibitors is that levels of the cholesterol-lowering drugs will increase in your body. This can cause a rare muscle condition called rhabdomyolysis, destroying skeletal muscles in your legs, butt and arms.

So for now, until there are further data, if you and your doctor believe it is necessary to treat high cholesterol levels with statins while on protease inhibitors, Pravachol and Lescol are the safest bets. By the way, Pravachol lowers cholesterol more than Lescol.

See also Freak Fat and the 3d Network Report on the Geneva Conference.

NTZ-STILL PROMISING BUT UNIMED WALKS!
by James Learned

In early May, an FDA Advisory Committee recommended that the FDA not approve Unimed's NTZ (brand name Cryptaz). The committee asked for more analysis of the data Unimed presented, but when Unimed went to the FDA again in mid-June, the company's application was strongly rejected once again.

The PWA Health Group has been importing NTZ (nitazoxanide) for PWAs with cryptosporidiosis for over two years. Our decision to carry NTZ was based on a numberof factors: the lack of effective treatments for this debilitating, and sometimes fatal, parasitic infection; promising results from small trials in PWAs in Mali and Mexico; the lack of serious side-effects, toxicities or drug interactions; and the refusal of the drug's manufacturer, Unimed, to open large enough clinical trials and an ethical compassionate use program for PWAs who needed access to the drug.

Unimed is now doing virtually nothing; there are no new studies of the drug planned. Certainly, there are fewer cases of cryptosporidiosis and microsporidiosis at present due to combination therapy; this perceived smaller market doesn't encourage drug development for opportunistic infections. Unimed's data were abysmal-not because NTZ might not be effective, but because the trials were problematic in design, analysis was almost non-existent, and the number of people studied extremely small (228 people, with only 67 meeting the criteria required to figure out whether or not the drug worked). Unimed presented data based on its open-label compassionate use program-that's all! The bottom line is that none of us know how effective NTZ is in fighting crypto or micro or even the diarrhea caused by these parasites. We don't even know the correct dose if the drug is effective.

The somewhat good news: Unimed's NTZ compassionate use program is still open, at least for the time being. Your doctor has to enroll you and get approval from his or her IRB (Institutional Review Board). You must have documented crypto and be over age 3, but there's no longer any set T-cell criteria. The dosage you'll receive once your doctor has filed the necessary paperwork will be either 1,000 mg or 2,000 mg per day-the dose isn't up to or your doctor. In other words, you may receive a suboptimal dose. After four weeks, Unimed will adjust your dose upward if you have shown no clinical improvement. Unfortunately, Unimed's ethics have not improved. Call Sandy Faulkner at Unimed: (800) 864-6330 x3032.

If Unimed closes the compassionate use program and/or conducts no further studies of NTZ, we have useful strategies as a community to demand access. The company has only three approved products. Between marinol for weight loss, maxaquin, used for urinary and respiratory tract infections, and andranol, an anabolic steroid, their market is us! These products can be substituted with other company's products to varying degrees (or, in the case of marinol, with medical marijuana). According to Senior Vice President Robert Dudley, Unimed is exploring other options" for NTZ, "including future work," a vague statement, to say the least, that doesn't bode well for NTZ's future. We have to watch Unimed carefully. If NTZ is studied intelligently, we may have the first effective treatment for crypto. The worst case scenario? Well, we still don't know. Meanwhile, the PWA Health Group continues to import NTZ from Mexico for people who need it.

RIBAVIRIN APPROVED WITH A BIG FAT PRICE By John Falkenberg

On June 3rd, Schering-Plough announced that they had received FDA approval to market a combination of ribavirin and interferon alpha for the treatment of hepatitis C. This approval was granted for people with hepatitis C, who had previously responded to interferon alone but relapsed, meaning their "liver enzymes" went back up after treatment. The PWA Health Group has been importing ribavirin since the late 80s.

In Folks Experiencing Relapse
This approval was granted based on two clinical trials, one in the United States (153 people) and one international study (192 people). Volunteers with hepatitis C who had relapsed after being treated with interferon alpha alone were given either interferon alone again, or interferon in combination with ribavirin for 24 weeks. Participants were then followed for an additional 24 weeks after therapy was completed. The primary laboratory test used to determine if the treatment was successful was hepatitis C RNA (also known as hepatitis C viral load or PCR; a marker of viral activity). This laboratory test cannot measure viral load levels below 100 copies per ml. Therefore, anything below 100 was considered a response. This does not necessarily mean that the virus is gone but that viral activity is at very low levels.

The results of the U.S. and international studies were similar. In the U.S. 43% of those on the combination therapy experienced a viral load response, meaning hepatitis C viral load fell below 100 both at the end of 24 weeks of treatment and at the end of the 24 week follow-up period. Only 4% of those treated with interferon alone had a response. In the international study, 48% of those on the combination had a viral load response, far better than the 5% on interferon therapy alone.

Preliminary Results In Those Not Previously Treated
Schering-Plough has also announced positive results from a clinical trial in those with hepatitis C who have not been previously treated. These data have yet to be published. The two studies in this group of volunteers were similar to those described in those who relapsed except there were groups treated for a longer period, 48 weeks. Once again, participants were assessed for viral activity 24 weeks after treatment was completed. In those treated for 48 weeks with the combination therapy, 41% experienced a response (viral load below 100) versus 16% on interferon alone. In those treated for 24 weeks, the response rate was 33% for the combination versus 6% with interferon alone.

In mid-June, Schering-Plough applied to the FDA to expand the approval of combination ribavirin and interferon to include those who have yet to be treated. This approval could be granted by year-end. It is important to note that there are no data, to date, on interferon plus ribavirin treatment in those co-infected with hepatitis C and HIV.

The High Cost of Therapy
Schering-Plough not only launched ribavirin at a high price but they are packaging it together with their own brand of interferon which limits the choice of which interferon can be used in combination therapy. The brand name of ribavirin is Rebetol. The brand name of Schering's interferon alpha is Intron A. They are packaged together as a treatment for hepatitis C, called Rebetron.

Before Rebetron, the most common treatment for hepatitis C was 3 million IUs of interferon injected subcutaneously (under the skin), three-times weekly, for 24 weeks. At the average wholesale price, this treatment costs approximately $2,500. The approved Rebetron dose includes the same dosing scheme of interferon plus oral ribavirin 1,200 mg daily for those who weigh more than 75 kg, (165 lbs) or 1,000 mg daily for those 75 kg or less. The average wholesale price of 24 weeks of Rebetron treatment, depending on the individual's weight, ranges from approximately $7,800 to $8,600! Therefore, 24 weeks of ribavirin therapy has been priced at $5,300 (for 1,000 mg per day) to $6,100 (for 1,200 mg per day)!!

The PWA Health Group helps people import "Vilona", ribavirin manufactured by ICN pharmaceuticals, from Mexico under the FDA's Personal Import Regulations. Our price is $82 per box of 18, 400 mg tablets. Treatment for 24 weeks at 1,200 mg daily, costs approximately $2,300.

Schering's price is 265% greater than what's available through Mexico. That's quite a premium considering they simply conducted 24 to 48 week clinical trials in approximately 2,000 people. No wonder they recently renegotiated for exclusive worldwide rights to market oral ribavirin for hepatitis C. Analysts estimate that revenues from Rebetron will approach $1 billion in four years! Did anyone need another example of out-of-control drug prices? Well, here it is.

HAAC CALLS FOR ACTION IN FIGHT AGAINST HVC!
A new national direct action group called HAAC (Hepatitis C Action and Advocacy Coalition) has been formed in San Francisco. The group's mission statement says it all:

HAAC is a grassroots, all-volunteer group of individuals committed to non-violent direct action to end the Hepatitis C (HCV) crisis. We work to provide access to life-extending treatments to PEOPLE WITH HCV, foster effective prevention efforts, encourage sound public health policies, and ensure prevention of HCV. We work cooperatively with government and industry when progress is being made, and take to focused non-violent direct action when progress is stalled. We accept no money from pharmaceutical companies. Ending the HCV crisis is our highest priority.

Contact HAAC at:

530 Divisadero Street, #162
San Francisco, CA 94117
Email: haac_sf@hotmail.com.

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copyright 1998 by People With AIDS Working For Health, Inc.
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last modified: 9/21/98