Monthly Archives - April 2006

Hope for those with no options

For those of you trying to get on two active drugs….

You can get TMC 114 in expanded access. It is taking about 3 weeks to get it if the doctor knows the process. No T cell limit but your doctor has to prove that you have multi drug resistance. Three hours of paper work. Your doctor does not get paid for that time. Many doctors refused to be part of this system. To see who is listed in your area, email info@veritasmedicine.com and read
http://clinicaltrials.gov/ct/show/NCT00245739?order=1

Remember: TMC 114 will probably be approved in a month or so. TMC 114 is a second generation protease, and not a replacement to Fuzeon. Some people may be thinking about taking this drug with Merck’s integrase (info below) to get off Fuzeon. We really do not know much about how to compare a Fuzeon containing regimen with this one.

Never start a new agent on top of a failing regimen. This is called virtual monotherapy and only works for a little while. Read more here
http://salvagetherapies.org/announcements.htm

If you have multidrug resistance and very low T cells…like under 10, you can qualify for a single patient access program that requires a lot of work from your doctor. Most doctors do not know how to do it. Read the last link about that.

The Merck integrase study is now enrolling fast in phase III. This is a very promising drug (MRK518). They allow the use of TMC 114 in expanded access. Bad news: you have a 33% chance of placebo but they will give you the real thing in 16 weeks if your viral load is not undetectable then.

You can find out more about this here
http://benchmrk.com/secure/investigator_sites/sites.html

This product MAY be in expanded access by the end of the year if Merck enrolls the study fully by then.

Pfizer’s oral entry inhibitor Maraviroc: we are waiting to hear from the company to see if this product is a go or no go for treatment experienced patients. We will not know until they unblind their study in August.

Email me if you have any questions since this can be very confusing.

You can read some people’s testimonials at
http://salvagetherapies.org/testimonials.html

Consensus Statement on the Pricing of TMC114 /Darunavir

Consensus Statement on the Pricing of TMC114 /Darunavir
April 17, 2006

TMC114/darunavir will soon become Tibotec’s first licensed drug for the treatment of HIV disease. It is likely to be the first of several important anti-HIV drugs from Tibotec. To date, the HIV/AIDS community’s relations with Tibotec have been exemplary as the company has shown an exceptional willingness to invite and listen to input from people affected by HIV disease. Based on everything we know now, the licensure of TMC-114/darunavir will be a worthy addition to our anti-HIV armamentarium, especially for people who have developed resistance to the existing protease inhibitors.

This good news, however, does not exist in a vacuum. Instead, it will be played out against a background of growing national and international crises in the cost of health care. The cost of a typical anti-HIV regimen in United States has risen to $15,000 or more for initial therapy, while the cost of salvage therapy can easily reach three times that amount. This is just for cost of the drugs. These costs plus the cost of associated medical care must be supported for decades to come for every single person with HIV disease. Better drugs, like TMC114/darunavir, result in longer lives and thus even longer times on therapy. If the average duration of therapy is limited to no more than 50 years per person, the costs of HIV drugs over this period will easily exceed a trillion dollars in the US alone, not even counting future price increases. Add in a reasonable cost for the vast numbers needing therapy in developing nations and the overall cost of drug for treating HIV disease worldwide could easily equal the current US national debt. Clearly, the path we are on is not sustainable, at least not for anyone other than the pharmaceutical industry.

At a time when evidence of responsible citizenship is needed from the pharmaceutical industry, we have instead been treated to ever increasing prices with each new drug. Two recently approved protease inhibitors, Reyataz and Aptivus, leapfrogged each other in setting new pricing thresholds, quickly reaching a price nearly three times that charged for Crixivan when it offered the first real breakthrough in AIDS treatment in 1996. TMC114/darunavir is the next drug in line and all eyes will be on it the day its price is announced. Its net price must include the cost of a booster drug, Norvir from Abbott Labs, whose price was recently increased by 400% in another demonstration of reckless civic behavior by a pharmaceutical company. While Tibotec isn’t responsible for the price increases taken by others, it is responsible for the decision to use the Norvir booster. Tibotec now has two choices. It can either follow in the footsteps its predecessors, defying the needs of patients and taxpayers, or it can make a bold statement that shows that the industry will do its part to restrain the cost of healthcare. Make the wrong choice and all of the company’s efforts to maintain strong relationships with the government and the community will have been for naught. The cycle of ever increasing costs, and ever higher profits, will once again be validated. Is this the legacy that Tibotec wishes to create?

Since it was formed in 1998, the Fair Pricing Coalition has sought drug pricing that is cost neutral. We seek to avoid having each new drug push the cost of treatment upward. In the case of TMC114/darunavir, this leads to a very specific demand: we ask that the price charged for TMC114/darunavir should be less than or equal to the current price of Kaletra, which is presently the best selling protease inhibitor and the drug that TMC114/darunavir is most likely to replace in clinical practice. Since Tibotec has chosen to use a ritonavir booster to improve the bioavailability of TMC114/darunavir, the price must include its cost, just as the ritonavir booster is already included in the price of Kaletra.

We also expect substantial discounts over and above the minimum required by law for the AIDS Drug Assistance Program and other government payers. We trust that separate negotiations are underway with the appropriate representatives of those programs, but we hope to establish the baseline for those discussions with the pricing principles laid out here.

We urge the leadership of Tibotec Research, Tibotec Therapeutics, and parent companies Ortho and Johnson & Johnson to give this proposal the most serious possible consideration. We believe that the company will benefit greatly from agreeing to this request. It will establish the company both as a scientific leader and also as a civic leader. It will stand as evidence to the taxpayer and to the Congress that the pharmaceutical industry is capable of more than simply seeking the greatest possible profits without regard for the impact on society. Perhaps most importantly, it will be welcomed and appreciated by the people with HIV and the medical professionals who treat them. It will almost certainly generate positive press about a “new, more responsible attitude” by industry. And, we believe, it will encourage the fastest possible uptake of the drug into clinical practice. Tibotec is aware, no doubt, that recent Medicare Part D formulary guidance issued by the Centers for Medicaid and Medicare services, has changed the mechanism for adding newly FDA approved drugs in the six protected classes, including anti-retrovirals, as of April 17, 2006. Any drug approved by the FDA after April 17 must be approved for inclusion in the individual plan formulary by that plan’s Pharmacy and Therapeutics (P & T) committee. Drugs included in a protected class will have a expedited approval time that can take up to 90 days or three months, but there is no guidance suggesting that newly approved drugs in the protected classes must automatically be added to the plan formulary. Each state will likely take price into account along with therapeutic value. Additionally the P& T committees will make decisions as to how to tier new drugs for co-payment amounts. Because of their price, most of the newer anti-retrovirals are tiered in the highest tiers making them unaffordable for many. Therefore, if Tibotec hopes to see a rapid inclusion in formularies, they must price it aggressively. How state authorities and the HIV affected public feel about the pricing of new drugs will contribute to the speed of this process. At the state level, price will almost certainly be a key consideration. Meeting the goal described here will make it possible for the activist community to support the fastest possible acceptance on the formularies.

The payers, Congress, patients and providers are greatly frustrated with the pricing practices of the pharmaceutical industry. While patients and payers are struggling year after year to raise the money needed to obtain access for a growing patient population, the pharmaceutical industry has shown virtually no restraint in its quest for profits and shareholder benefits. Its profitability ranks among the highest of all industries while the percentage of revenues devoted to research and development are at best average. The pharmaceutical industry speaks proudly of the need for a “free market economy” and the benefits of competition, but in fact it behaves more like a group of monopolies. It accepts little or no pressure on prices as a result of competition, the cornerstone of a market driven economy. In the US, the industry funds massive political lobbying to prevent government from negotiating prices for the largest national payers. Unlike other industries, in which high profits are usually the result of the consumers’ selection of outstanding products, the “buyers” of pharmaceutical products have little choice in the selection of products and product quality bears no relationship to the price charged. This coercive relationship between buyer and seller can no longer be tolerated. It must be challenged, whether through consumer protest, eventual price controls, or payer product selection, none of which are very attractive to industry. Make the right choice now and none of these approaches will be necessary.

We will follow-up this letter with continued discussions and one or more face to face meetings with Tibotec. The list of signers supporting this position will be updated weekly.

[list in formation]

Regards,

Nelson Vergel
powerusa dot org

“I learned that…no one is perfect but most people are good; that people can’t be judged only by the worst or weakest moments; that harsh judgements can make hypocrites of us all; that a lot of life is just showing up and hanging on; that laughter is often the best, and sometimes the only response to pain.” My Life by Bill Clinton

—————–
Forwarded Message:
Subj: Request for Sign-On New HIV Drug Pricing Consensus Statement
Date: 4/19/2006 3:44:46 P.M. Central Standard Time
From: Leichou

Please help distribute widely, apologies for duplicates.

Pricing of pending new HIV drug critical to domestic treatment access,
Now is the time to impact the pricing decision by Tibotec,
Join the Fair Pricing Coalition’s consensus statement

The new anti-HIV drug TMC114/darunavir made by Tibotec is expected to receive FDA approval this summer. This drug is particularly important because clinical trials have shown it to work against highly resistant strains of HIV. Access to this drug is a matter of life and death for many people, particularly long-term survivors.

As shown by recent pricing decisions by other HIV drug makers, the industry trend is to price new therapies at record high levels. The prices of the last two protease inhibitors, Reyataz from Bristol Myers Squibb and Aptivus from Boeringher Ingelheim, bring the price of protease inhibitors alone to well over $10,000 and the cost of a typical regimen in excess of $16.000. With drug prices like these, we may never be able to get adequate funding for ADAP and the Ryan White program.

The escalation in the price of prescriptions drugs MUST STOP NOW if there is ever to be a hope of bringing treatment to all in need.

We believe that we have a good chance of reversing the upward spiral of prices with this company and this drug, but only if we raise sufficient public pressure before the price is set. Please join us and our organizations to help make this a reality. Directly or indirectly, it affects every other battle over government funding for HIV.

Thank You,

Martin Delaney, for Project Inform
Lei Chou, for Community HIV/AIDS Mobilization Project
Lanny Cross
Mark Harrington, for the Treatment Action Group
Lynda Dee, for AIDS Action Baltimore
Dennis deLeon, for the Latino Commission on AIDS
Matt Sharp, for the Test Positive Aware Network
Bob Huff, for Gay Men’s Health Crisis (GMHC)
William E. Arnold, for Title II Community National AIDS Network

To sign on to this consensus statement, please send the following information to leichou@aol.com

Name:
Organization:
Address:
City:
State:
Zip:
Phone:
email:

Consensus Statement on the Pricing of TMC114 /Darunavir
April 17, 2006

TMC114/darunavir will soon become Tibotec’s first licensed drug for the treatment of HIV disease. It is likely to be the first of several important anti-HIV drugs from Tibotec. To date, the HIV/AIDS community’s relations with Tibotec have been exemplary as the company has shown an exceptional willingness to invite and listen to input from people affected by HIV disease. Based on everything we know now, the licensure of TMC-114/darunavir will be a worthy addition to our anti-HIV armamentarium, especially for people who have developed resistance to the existing protease inhibitors.

This good news, however, does not exist in a vacuum. Instead, it will be played out against a background of growing national and international crises in the cost of health care. The cost of a typical anti-HIV regimen in United States has risen to $15,000 or more for initial therapy, while the cost of salvage therapy can easily reach three times that amount. This is just for cost of the drugs. These costs plus the cost of associated medical care must be supported for decades to come for every single person with HIV disease. Better drugs, like TMC114/darunavir, result in longer lives and thus even longer times on therapy. If the average duration of therapy is limited to no more than 50 years per person, the costs of HIV drugs over this period will easily exceed a trillion dollars in the US alone, not even counting future price increases. Add in a reasonable cost for the vast numbers needing therapy in developing nations and the overall cost of drug for treating HIV disease worldwide could easily equal the current US national debt. Clearly, the path we are on is not sustainable, at least not for anyone other than the pharmaceutical industry.

At a time when evidence of responsible citizenship is needed from the pharmaceutical industry, we have instead been treated to ever increasing prices with each new drug. Two recently approved protease inhibitors, Reyataz and Aptivus, leapfrogged each other in setting new pricing thresholds, quickly reaching a price nearly three times that charged for Crixivan when it offered the first real breakthrough in AIDS treatment in 1996. TMC114/darunavir is the next drug in line and all eyes will be on it the day its price is announced. Its net price must include the cost of a booster drug, Norvir from Abbott Labs, whose price was recently increased by 400% in another demonstration of reckless civic behavior by a pharmaceutical company. While Tibotec isn’t responsible for the price increases taken by others, it is responsible for the decision to use the Norvir booster. Tibotec now has two choices. It can either follow in the footsteps its predecessors, defying the needs of patients and taxpayers, or it can make a bold statement that shows that the industry will do its part to restrain the cost of healthcare. Make the wrong choice and all of the company’s efforts to maintain strong relationships with the government and the community will have been for naught. The cycle of ever increasing costs, and ever higher profits, will once again be validated. Is this the legacy that Tibotec wishes to create?

Since it was formed in 1998, the Fair Pricing Coalition has sought drug pricing that is cost neutral. We seek to avoid having each new drug push the cost of treatment upward. In the case of TMC114/darunavir, this leads to a very specific demand: we ask that the price charged for TMC114/darunavir should be less than or equal to the current price of Kaletra, which is presently the best selling protease inhibitor and the drug that TMC114/darunavir is most likely to replace in clinical practice. Since Tibotec has chosen to use a ritonavir booster to improve the bioavailability of TMC114/darunavir, the price must include its cost, just as the ritonavir booster is already included in the price of Kaletra.

We also expect substantial discounts over and above the minimum required by law for the AIDS Drug Assistance Program and other government payers. We trust that separate negotiations are underway with the appropriate representatives of those programs, but we hope to establish the baseline for those discussions with the pricing principles laid out here.

We urge the leadership of Tibotec Research, Tibotec Therapeutics, and parent companies Ortho and Johnson & Johnson to give this proposal the most serious possible consideration. We believe that the company will benefit greatly from agreeing to this request. It will establish the company both as a scientific leader and also as a civic leader. It will stand as evidence to the taxpayer and to the Congress that the pharmaceutical industry is capable of more than simply seeking the greatest possible profits without regard for the impact on society. Perhaps most importantly, it will be welcomed and appreciated by the people with HIV and the medical professionals who treat them. It will almost certainly generate positive press about a “new, more responsible attitude” by industry. And, we believe, it will encourage the fastest possible uptake of the drug into clinical practice. Tibotec is aware, no doubt, that recent Medicare Part D formulary guidance issued by the Centers for Medicaid and Medicare services, has changed the mechanism for adding newly FDA approved drugs in the six protected classes, including anti-retrovirals, as of April 17, 2006. Any drug approved by the FDA after April 17 must be approved for inclusion in the individual plan formulary by that plan’s Pharmacy and Therapeutics (P & T) committee. Drugs included in a protected class will have a expedited approval time that can take up to 90 days or three months, but there is no guidance suggesting that newly approved drugs in the protected classes must automatically be added to the plan formulary. Each state will likely take price into account along with therapeutic value. Additionally the P& T committees will make decisions as to how to tier new drugs for co-payment amounts. Because of their price, most of the newer anti-retrovirals are tiered in the highest tiers making them unaffordable for many. Therefore, if Tibotec hopes to see a rapid inclusion in formularies, they must price it aggressively. How state authorities and the HIV affected public feel about the pricing of new drugs will contribute to the speed of this process. At the state level, price will almost certainly be a key consideration. Meeting the goal described here will make it possible for the activist community to support the fastest possible acceptance on the formularies.

The payers, Congress, patients and providers are greatly frustrated with the pricing practices of the pharmaceutical industry. While patients and payers are struggling year after year to raise the money needed to obtain access for a growing patient population, the pharmaceutical industry has shown virtually no restraint in its quest for profits and shareholder benefits. Its profitability ranks among the highest of all industries while the percentage of revenues devoted to research and development are at best average. The pharmaceutical industry speaks proudly of the need for a “free market economy” and the benefits of competition, but in fact it behaves more like a group of monopolies. It accepts little or no pressure on prices as a result of competition, the cornerstone of a market driven economy. In the US, the industry funds massive political lobbying to prevent government from negotiating prices for the largest national payers. Unlike other industries, in which high profits are usually the result of the consumers’ selection of outstanding products, the “buyers” of pharmaceutical products have little choice in the selection of products and product quality bears no relationship to the price charged. This coercive relationship between buyer and seller can no longer be tolerated. It must be challenged, whether through consumer protest, eventual price controls, or payer product selection, none of which are very attractive to industry. Make the right choice now and none of these approaches will be necessary.

We will follow-up this letter with continued discussions and one or more face to face meetings with Tibotec. The list of signers supporting this position will be updated weekly.

I have updated my web sites and internet discussion groups!

Lipodystrophy, Wasting, Hormones, Exercise, Nutritrion

www.medibolics.com

Therapies for people failing HIV treatments

www.salvagetherapies.org

Nelson Vergel’s personal web site

www.nelsonvergel.com

Subscribe to the largest Internet discussion group by sending a blank email to

pozhealth-subscribe@yahoogroups.com

If you are taking Fuzeon or planning to, send a blank email to

FuzeonSupport-subscribe@yahoogroups.com

If you have failed most of your HIV medications and you want to talk to others going through the same challenge, send a blank email to

Salvagetherapies-subscribe@yahoogroups.com

Interview with Dr Jon Kaiser about his supplement

By Nelson Vergel

Jon D. Kaiser, M.D., has been a leader in promoting the integration of natural immune system support with state of the art standard medical therapies for HIV. He is also the author of Healing HIV: How to rebuild your immune system (1999 HealthFirst Press). All of Dr. Kaiser’s current treatment guidelines and current research activities can be followed at www.jonkaiser.com.

I felt compelled to ask Dr. Jon Kaiser to give us his input on micronutrient use for the management of mitochondrial toxicity. Differing with Dr. Walker from Germany, Dr. Kaiser in San Francisco has positive experience with the use of simple micronutrients available over the counter in the US.

NV: Thank you Dr. Kaiser for taking the time to answer these questions. Could you tell us about your protocol for mitochondrial toxicity? What supplements are you using and at what dose? What variables are you looking at?

JK: Nelson, first let me commend you on the questions you submitted. They are both probing and insightful. It is my belief that mitochondrial toxicity is a severe problem which potentially affects every HIV(+) patient taking a reverse transcriptase inhibitor (RTI) (i.e. D4T, AZT, DDI, abacavir, etc.).

As is commonly known, the mitochondria are the power plants inside every cell that produce the energy required for healthful functioning. The RTI class of medications significantly blocks a mitochondrial enzyme whose sole purpose is to assist the mitochondria in producing the building blocks necessary to produce this energy.

As this enzyme is poisoned, the ability of the mitochondria to break down the toxic waste products of normal energy metabolism diminishes. These toxic waste products are known as “free radicals” and they contain highly charged oxygen atoms which are poisonous to the cells. As this process progresses over time, the level of free radicals increases to dangerous levels.

NV: Is there anything that can be done to prevent or reverse the buildup of these toxic free radicals in the mitochondria?

JK: The level of vitamins and antioxidants we consume as part of a normal diet are only adequate for detoxifying free radicals in a system that is not under stress. Once you add HIV infection, plus the use of RTI antiviral drugs, to a person’s system, the level of toxic free radicals rises dramatically and begins to cause system-wide toxicity which can ultimately lead to neuropathy, pancreatitis, liver problems, fat atrophy, lactic acidosis, amongst others.

I have been testing different combinations of antioxidants for the past several years in an attempt to identify which ones most effectively reduce the incidence of mitochondrial toxicity. Fortunately, I believe I have found a combination that, not only reduces antiviral medication side effects, but also provides the immune system with enhanced levels of energy and vitality.

This combination of antioxidants includes high doses of NAC, alpha lipoic acid, and acetyl L-carnitine, supported by a base of B-complex, vitamin C, Calcium, Magnesium, Zinc, and Selenium. After experimenting with different formulas, I have been so pleased with the beneficial effects of the current formula that my previous recommendation to include coenzyme Q-10 in the program has been dropped without any apparent loss of benefit. Leaving out coenzyme Q-10 has however allowed the overall cost of the formula to be reduced.

The exact formula that I have been using with my patients during the past three years for preventing mitochondrial toxicity with excellent results can be viewed on my website at www.jonkaiser.com. The dosage is based on a person’s weight. HIV(+) patients who weigh greater than 145 lbs. should take twice the dosage of HIV(+) patients who weigh less than 145 lbs. I have found this weight cutoff to work the best.

It is my opinion that HIV(+) patients taking this formula of nutrients experience far fewer medications side effects including peripheral neuropathy, fat atrophy, pancreatitis, liver inflammation, etc. Furthermore, I often observe a CD4 count boost of approximately 15-20 percent within a few months after beginning this formula.

NV: In your opinion, can micronutrients possibly prevent neuropathy for someone starting “D” drugs?

JK: In my opinion, there is no doubt that the right combination of quality antioxidants can block this mitochondrial toxicity process. My opinion is based on the past three years of reviewing the latest research combined with my clinical experience in over 500 patients following my protocol.

NV: Is there a difference between vitamin brands and manufacturing standards?

JK: Without a doubt. As I began the process of manufacturing my formula for a clinical study, I learned a great deal about how vitamin supplements are produced. In essence, vitamin supplements can be produced cheaply, using inferior raw materials, mixing them with wax so they can be pressed into less expensive tablets that don’t break down easily in the gut, or they can be produced to extremely high quality, pharmaceutical-grade standards that use the highest quality raw materials possible.

NV: In addition, the antioxidants I mentioned above (NAC, alpha lipoic acid, and acetyl L-carnitine) are extremely sensitive to heat, light, and most importantly, exposure to air. Antioxidants react vigorously with oxygen. Therefore, if they are not protected from the air and kept in cold long term storage, they will degrade over time.

JK: I guarantee that the manufacturing of my formula by IHC Vitamins applies these pharmaceutical-grade standards to every batch. They use the highest quality raw materials, are mixed into quick dissolving capsules, are sealed into single dose convenient packets and are kept in cold storage until shipment. I have direct oversight of the quality control process and every batch is tested for potency by a nationally accredited reference laboratory.

These are the same nutrient packets currently being tested in my research studies. To view the study protocol visit www.jonkaiser.com and click on the research button.

NV: What is the monthly cost of your mitochondrial toxicity prevention formula?

JK: As I mentioned above, the recommended dose of my formula is based on a person’s weight and health status. HIV(+) patients who weigh greater than 145 lbs. should take a double-strength packet twice daily while those weighing less than 145 lbs. should take a single-strength packet twice daily.

The current cost to individuals for a month’s supply of single strength packets is $84.95 per month while the cost for a month’s supply of double strength packets is $142.95 per month. In my opinion, this program provides all the micronutrients an HIV(+) person needs to take for optimal immune system support.

Buyers clubs and non-profit organizations can order the vitamins for their members at a substantial discount (30% off) and I am working hard to get the cost down even further as quickly as possible without compromising the high quality standards.

NV: Are you looking at the effect on fat cells under the skin? If not, do you know anyone doing research on supplements that may prevent lipoatrophy?

JK: The proposed mechanism…that fat atrophy in the face and extremities is due to the buildup of reactive oxygen species (free radicals) in the fat cells…is plausible and substantiated by a significant amount of research to date. There may be other factors as well, but the buildup of free radicals in fat tissue will cause apoptosis (cell death) to fat cells as just as effectively as it causes it to other types of cells.

A study which has yet to be done is to give a large group of patients just beginning antiviral therapy high-dose antioxidants, compared to a second group that gets a placebo. They should then be followed for at least 3-5 years with close monitoring. In my opinion, the high-dose antioxidant group will have fewer side effects (including lipoatrophy) and will require less frequent changes to their antiviral therapy due to resistance.

NV: Have you observed any improvements in metabolic parameters, lipids, etc.?

I have yet to see a patient taking my micronutrient formula develop diabetes due to antiviral medications. Cholesterol and triglycerides are another story. Increases in these parameters is most probably not due to a mitochondrial toxicity mechanism.

NV: In your assessment of neuropathy, what tool did you use?

JK: I used a questionnaire called the NILAS, plus a physical exam assessing the effect on light touch, pain, and vibratory sense to measure the degree of peripheral neuropathy present. The NILAS is a linear scale from 0 to 100 that asks three questions and is scored based on the patient’s subjective responses.

NV: Do you think there may be a possibility for BMS to provide supplements that enable people to take D4T and DDI in the long term as part of their product? I remember when adefovir was provided with Carnitine when it was studied for HIV.

JK: Yes, it is the goal toward which I am fervently working. However, high quality research needs to be performed which supports any benefit claims before they will consider this proposal.

NV: . If you had unlimited funds for research, what would you study and why?

JK: That’s easy. First, I would design a large research study that gave patients beginning antiviral medication for the first time either my vitamin packets or a placebo packet to be taken twice daily with food. Then I would follow both groups for as long as possible (at least 3-5 years) and carefully observe the incidence of drug related side effects as well as immunologic parameters such as CD4 cells and how often the patients needed to switch their antiviral regimens due to drug failure. I’m pretty sure the vitamin group would show clear benefits in several areas.

Next, I would do a study in an under-developed area, such as Africa, to test whether a combination of high-dose micronutrients, plus a daily protein supplement, could slow the progression of HIV in patients not taking antiviral medication. The use of this type of nutritional support could stabilize a large percentage of the population until the availability of antiviral medications had increased. My experience leads me to believe that this type of intervention would work very well.

NV: Are there any other natural treatments that you believe make a big difference in the long term health and wellbeing of an HIV(+) individual?

JK: Yes. I check a body composition test (BIA) on my patients every six months and strive to keep their muscle mass in the 40-44 percent range for HIV(+) men and the 30-34 percent range for HIV(+) women. This helps maintain solid energy production by the body and optimally supports the immune system.

While I believe accomplishing this naturally utilizing protein supplements and resistance exercise is optimal, I often prescribe nandrolone, oxandrolone, and occasionally recombinant human growth hormone, if the situation warrants.

I also strongly encourage all HIV(+) individuals to get their free testosterone and DHEA-sulfate levels checked every six months as well. The optimal range for these depends on each individual’s needs, however a general rule of thumb is to keep these hormone levels within the upper half of the normal range. Both these hormones support energy production, mood, libido, and immune function.

By utilizing micronutrients and intelligent hormone supplementation, the immune system can be well supported, ultimately leading to less reliance on drugs and fewer HIV-related illnesses. The E-newsletter archives on my website (www.jonkaiser.com) provides in-depth articles on how to supplement each of these hormones to your greatest advantage (see issues 12/02 through 5/03).

NV: You have been a trendsetter in the HIV medical world. Do you think physicians would embrace the use of micronutrients as a pharmacological intervention for side effect management?

JK: Yes, I do. There would need to be one or two very compelling studies (which I hope to do) that attract other researchers who had an open mind to study the effects of high-dose micronutrients in HIV disease. Once other researchers become involved, I believe there would be a great deal of important data generated that would convince HIV treatment providers that micronutrients can provide real benefits.

Remember, HIV has always been a condition that has been able to break down barriers for patients needing to access new treatments. This is primarily because the scientific community is trying to improve the standard level of care which is presently unable to guarantee our patients long and healthful lives.

Thank you very much for allowing me to share this information with your readership.

NV: And thank you, Doctor.

Uridine- Nucleomaxx- A supplement that may help to reverse lipoatrophy- Interview with Dr Walker

I had the pleasure to meet Dr. Walker after his oral presentation on Uridine and mitchondrial toxicity at the Lipodystrophy Conference in Paris. I was very excited to see his in vitro data on how this supplement may protect liver cell mitochondria exposed to D4T (Zerit) and DDC (Hivid). He gladly agreed to be interviewed for our newsletter. I am looking forward to seeing more data on this exciting approach that may make it possible for many of us to take nucleosides without the long term mitochondrial toxicity related side effects.

Dr. Ulrich A. Walker underwent his medical school education at the University of Tübingen/Germany and at the University of Michigan (AnnArbor/ MI) and graduating in 1991. He recieved his specialization in Internal Medicine, Rheumatology and Allergology at the University of Freiburg/ Germany. He did postdoctoral studies (3 years) with focus on mitochondrial genetics and metabolism at the Neuromuscular Research Centre in Melbourne/ Australia and at Columbia University (NYC, NY). He has also been director of a research lab on mitochondrial genetics and metabolism since 1999 and is currently anAssociate professor in Internal Medicine at the University of Freiburg/Germany since 2003. Dr Ulrich has also been a consultant doctor and medical director of the HIV outpatient care unit at the University of Freiburg/Germany since 2000.

NV: Doctor Walker, What is Uridine?

UAW: Uridine is a particular “nucleoside” which is used by our body to produce DNA. Uridine is also required for many other metabolic pathways – for example uridine is needed to produce glycogen. Uridine is a natural substance in our body. Humans are normally able to produce uridine, but the ability to do so requires intact mitochondria.

NV: How does Uridine reduce mitochondrial toxicity caused by nucleosides?

UAW: Our current research supports the following concept: One class of anti-HIV drugs are the so called “nucleoside reverse transcriptase inhibitors” (NRTIs). As the name implies, the NRTIs are themselves nucleosides (“nukes”). The NRTIs are “bad nukes”, as they are toxic to mitochondria. This is because they inhibit gamma polymerase, an enzyme that is essential for the replication of mitochondrial DNA. As a consequence, the levels of mitochondrial DNA in mitochondria decline. Mitochondrial DNA however is necessary for the proper function of the respiratory chain (this is were we “breathe internally,” consume oxygen and make ATP as the energy for our body. Another consequence of respiratory chain dysfunction is that the body cannot make uridine and other natural nucleosides (the “good nukes”).

Therefore, the NRTI-nucleosides (“the bad nukes”) are more abundant in relation to the natural nucleosides (“the good nukes”) at gamma polymerase. This excess of the bad nukes makes mitochondrial function even worse, because a vicious circle is closed. Uridine replenishes the good nukes and therefore abolishes this vicious circle.

NV: Your research shows that the dose use invitro studies was 200 micromoles. What does that translate to in a 150 Lb man?

UAW: We have shown full protection at a concentration of 200 µM but there were some indications of improvement starting at about 50 µM. Other researchers looked at the effect of zidovudine (AZT) on blood cells in vitro and in mice and have shown protection at 50 µM.

Uridine can be bought at the chemist but the costs there are prohibitive to be used long-term by anybody. NucleomaxX is a dietary supplement that comes in sachets to be dissolved in water, milk or juice. It contains Mitocnol, a sugar cane extract with high amounts (18%) of nucleosides. We have discovered, that a single sachet of NucleomaxX increases the dose to more than 100 µM (for example in myself (190 Lb) to 105 µM. Repeated doses increase the serum concentrations even more.

NV: Your research so far shows promising results in liver cells that have been exposed to D4T, DDC, AZT+3TC. Are you planning to conduct studies to see the effect on fat, muscle and nerve cells?

UAW: Several studies looking at liver, fat, peripheral nerves, lactate, anemia and leucopenia in humans have been approved or are currently submitted.

NV: Are you currently performing any in vivo studies? If so, what are the variables you are looking at?

UAW: Other than the studies in humans discussed above, we are currently looking at mice, measuring mitochondrial DNA and mitochondrial function in every relevant tissue. We have not yet finished our experiments but I can say that the mice drink NucleomaxX without any apparent problem and that high uridine serum levels are achieved.

NV: What is the human dose?

UAW: We don’t know for certain yet. The experience from our in vitro work and from a very limited number of HIV-patients suggests that uridine resets the mitochondrial clock, thus supporting an intermittent dosing schedule. NucleomaxX is recommended to be taken on three consecutive days on each month. 7.
NV: How can anyone order the product?

UAW: Please refer to the NucleomaxX website www.nucleomaxX.com.

NV: Your research shows that Uridine may not work for mitochondrial toxicity related to DDI. Could you tell us why?

UAW: Nucleosides can be divided into two chemical classes, namely the “pyrimidines” (such as stavudine, zidovudine, zalcitabine, lamivudine) and the “purines”, such as DDI (didanosine). Uridine itself is also a pyrimidine and thus does not block vicious circles caused by purines at the mitochondrial gamma polymerase. 9. You mention that the use of supplements like carnitine , thiamine, riboflavin and Coenzyme Q-10 have shown disappointing results in protecting the mitochondria against nucleosides. The HIV positive community in the US is using these products a lot. Should we stop using them? What would the effect be in we combined these supplements with Uridine? Would they work synergistically?

We have tested the above-mentioned supplements in our system but did not find any benefit. You may continue these supplements if you like as they are not harmful. I just would not put too much hope (and money) into them. I have no information on synergism.

NV:. There was a concern that Uridine may affect blood levels of nucleosides. It seems that your in vitro studies show that Uridine may increase blood levels and enhance the antiviral effect of nucleosides. Could you elaborate?

UAW: The increase of uridine blood levels is a desired effect. Our in vitro work and work by others did not show a significant interaction with the anti-HIV efficacy of antiretrovirals, but I think this still needs a watchful eye.

NV: Even though Uridine improves mitochondrial function of liver cells exposed to DDC, it seemed that the mitochondrial DNA was not restored to baseline values. Does this have any significance?

UAW: Probably not. This is because mitochondria seem to work badly only when mitochondrial DNA drops below a certain threshold (about 20% of baseline). Therefore mitochondrial function in our experiments was fully restored despite the fact that the levels of mitochondrial DNA did not fully return to baseline.

NV: Could Uridine be used to prevent AZT induced anemia and leucopoenia?

UAW: Yes, studies in vitro and studies in mice have shown this.

NV: What are the potential side effects of Uridine?

UAW: The dose-limiting effect in Uridine studies so far was a mild diarrhea with excessive doses. The diarrhea stopped immediately when Uridine was discontinued. We have not yet observed this with NucleomaxX.

NV: You mentioned in Paris that the old studies of Uridine were done in IV formulations and that you have a more bioavailable oral formulation. Can you expand on this?

UAW: This is probably a misunderstanding because intravenous Uridine is more bioavailable than oral Uridine.

NV: Any plans for US studies?

UAW: One study will look at lipodystrophy under Stavudine and is currently being submitted.

NV: Thank you Doctor.

The Chipmunk look that noone talks about

I have been seeing many HIV positive men with enlarged parotid glands in my 14 years of travels giving lectures around the country. I was also one of those men with moderate inflammation of the parotid glands. No one really knows what causes this disfiguring inflammation. It could be due to the HIV virus itself, inflammatory cytokines and too many CD8 cells produced by immune reconstitution, hormones, fat build up in the glands, etc. Some people have this problem along with facial wasting, which makes their faces look very abnormal. So even if you treat your facial wasting with facial fillers, this problem needs to be treated so that you can attain a more normal look that resembles what you normally would look like without the effects of HIV and its medications. The parotid gland is the largest of the salivary glands that produce saliva that is important in the digestion of food. The gland lies under the angle of the jaw just beneath the ear. I have been searching for a long time for an answer. Not a single HIV conference has had a presentation on this problem that may affect around 20 percent of men with HIV. It does not seem to affect as many women with HIV for unknown reasons. I had heard about radiation treatments in the past but they created severe side effects like burning of the salivary glands, salivary production problems, and eventual tooth decay. A few months ago my dear friend Dr. Ton y Mills from Los Angeles called me to tell me about the great results he had seen in his patients referred to Dr Patricia Gordon. I decided to call Dr. Gordon myself to talk to her about her experiences. Dr. Gordon did her undergrad at Harvard and her residency at UCLA. She is a radiation oncologist and practices at Century City Hospital in Los Angeles. A very pleasant and seemingly dedicated doctor, she immediately told me how happy she was with the excellent remission rates she had been seen in her patients. Most noticed complete resolution of the problem after a few sessions of low dose electron-based radiation. She stressed the fact that this protocol differs greatly from the ones used in the past that created greater side effects because of the nature of the radiation, Unlike the old method that used photons that penetrate the skin more deeply, she uses electrons that penetrate a very thin layer of tissue instead, so they do not cause the burning and salivary gland dysfunction seen in the past. She has had over 200 male patients referred to her practice (not one female has been referred). At baseline, all patients get a CT scan of their parotid gland area for assessment. They get a customized molded lead mask that only exposes the area to be treated. They then receive 16 sessions (once a day for five days a week, for five minutes each) on both sides of the face. She said that most patients see improvements after four sessions. However, she did not have before and after pictures to share with me. All procedures have been reimbursable by Medicare and insurance. I decided to get my parotid glands treated and I am happy to say that they got back to normal after 7 sessions. It has been 4 years now (March 2006) and they are still normal ! I had no significant side effects besides redness for a few days, no beard for a month (which I liked), and a temporary loss of normal saliva production. All returned to normal after a month or so. I am not sure, but I think I had a slight decrease in CD4 cells (around 20) but this is hard to tell unless someone performs a controlled study. My CD4 cells also returned baseline after two months. Dr. Gordon will publish a paper on her experiences soon. Her phone number is 310-201-6739. Her email is _pgordonmd@aol.com_ (mailto:pgordonmd@aol.com) .She is happy to talk to doctors or patients about this procedure. (http://www.facialwasting.org/pages/891053/index.htm)

Face to Face with Lipoatrophy

Face to Face with LipoatrophyAn Interview with David Nolan

By Nelson Vergel

HIV-related lipoatrophy (fat loss under the skin) is a clinical problem that affects many people living with HIV. Lipoatrophy can cause substantial loss of buttock tissue, veiny legs and arms, and facial wasting. Lipoatrophy can happen alone or in combination with lipohypertrophy (fat accumulation) in the visceral (organ) and dorsocervical (back of the neck) area. These body changes, with or without blood level alterations of cholesterol, triglycerides, lactic acid, glucose, and insulin, is called HIV-related lipodystrophy syndrome.

Many of these body changes occur normally with aging, but being HIV positive seems to accelerate their development. Many observational cohorts and studies to determine the causes and potential treatments of lipodystrophy have been performed since 1997, the first year when we realized that living longer with HIV may be accompanied with side effects like body changes. Even though there is not yet a consensus-based case definition for lipodystrophy, there are many things that we have learned since then. One is the potential impact of nucleoside thymidine analogs like d4T (Zerit, stavudine) and AZT (zidovudine) on subcutaneous (under the skin) fat wasting. Studies in which patients were switched from these drugs to abacavir (Ziagen) or tenofovir (Viread) have produced encouraging results in reversing lipoatrophy, even if at a slow rate. Other studies looking at using insulin sensitizers like rosiglitazone (Avandia) to reverse lipoatrophy have produced conflicting results. It seems that the use of Avandia in combination with Zerit or AZT does not allow for regrowth of subcutaneous fat tissue. Fortunately, good news came to patients with lipoatrophy in the U.S. when the FDA approved Sculptra (polylactic acid) injections in August 2004 for the treatment of HIV related facial lipoatrophy. Although this option does not treat the root cause of the problem, it can give patients the hope of restoring a healthy appearance once again.

David Nolan is a clinician and researcher based at Royal Perth Hospital in Western Australia, where he works at the Centre for Clinical Immunology and Biomedical Statistics. He has a broad range of interests relating to HIV and its treatment, with a particular emphasis on lipoatrophy where he has explored associations between NRTI therapy, mitochondrial toxicity and fat tissue pathology. He has published more than 30 research papers and reviews, covering the broad topic of lipodystrophy as well as related topics including mitochondrial toxicity syndromes, metabolic complications of HIV protease inhibitor therapy, hyperlactatemia syndromes, genetic susceptibility to abacavir and nevirapine hypersensitivity reactions, and the effects of HIV and treatment on bone density.

Nelson Vergel: Can HIV itself cause lipoatrophy or mitochondrial dysfunction in treatment-naive patients?

David Nolan: There is no evidence that HIV infection itself can cause lipoatrophy. It has been known for some time that severe immune deficiency and AIDS-defining illnesses can be associated with “AIDS wasting,” but this is quite different in terms of the effects on body composition. Lipoatrophy specifically affects the fat tissue just under the skin surface (subcutaneous fat), leading to fat loss that is particularly noticeable over the legs, buttocks and face. It is also notable that the lean body mass (i.e., muscle tissue predominantly) is unaffected in the case of lipoatrophy, and indeed muscle mass often improves in the presence of lipoatrophy.

On the other hand, AIDS wasting associated with untreated HIV predominantly affects lean body mass while having less of an effect on fat tissue. The only exception here is that women with advanced HIV disease tend to lose fat as well as muscle, although again this has different characteristics. Loss of fat in AIDS wasting in women tends to be generalized (i.e., the same all over the body) as with any weight loss, while part of the reason that lipoatrophy is so noticeable in both men and women is the way in which fat loss is so “unevenly spread” over the body. For women in particular, the preferential loss of fat over the legs and buttocks associated with lipoatrophy is quite unusual.

Your lipoatrophy data on AZT shows only about half the adipocyte (fat cell) depletion that is asssociated with d4T. Do you think the depletion of fat cells and mitochondrial DNA/function warrants removing AZT from the treatment guidelines of industrialized countries for first-line therapy?

This is a very interesting question and one where there is no definitive answer yet. The adipocyte depletion findings tell some of the story, although the clinical data are probably more important in showing how significant the effect of AZT is in terms of lipoatrophy risk. Overall, the severity of fat loss — and the risk of clinical lipoatrophy — is approximately halved with zidovudine treatment compared to stavudine. This means that in “ball park” terms, the risk of developing noticeable fat loss is 15 percent to 20 percent after 3 to 5 years of zidovudine treatment.

My own view (and again there is no consensus opinion available as yet) is that the impact of zidovudine treatment is not sufficient to minimize its use for first-line therapy in industrialized countries. There are a number of reasons:

The fat loss associated with zidovudine treatment tends to be fairly slowly progressive, typically beginning after the first year of treatment with the greatest risk of fat loss between 12-36 months. In this instance, if those taking AZT (and those clinicians treating them) are aware of the risk of lipoatrophy and actively monitor for early signs (i.e., fat loss that particularly affects the legs, buttocks and/or face, and which is often not associated with any loss of weight), then treatment can be altered if and when this complication develops. We know from the results of “NRTI switching” studies involving the use of abacavir or tenofovir that fat loss is at least halted, and often improves, when the NRTI drugs are changed.
There are host and disease factors that also contribute to the risk of lipoatrophy when AZT or d4T are used (although, as stated above, these risk factors only operate when these drugs are used). Therefore, the risk of lipoatrophy with AZT treatment is likely to be substantially reduced in those who are younger than 35 years of age, who are of non-white racial origin, and who start treatment when the CD4+ T cell count is greater than 100–200.
Finally, I think that part of the reason that AZT has remained in continuous clinical use since 1987 is that it has a favorable resistance profile in terms of its interaction with other NRTI drugs. The available data for newer “backbone” NRTI drugs such as tenofovir and abacavir is certainly very promising, but there are still some questions regarding both their long-term effectiveness and (to a lesser extent) the potential for tenofovir to cause renal and/or bone toxicity.
For those who want to start or remain on a non-protease inhibitor combo, AZT seems to have a protective role in the selection for K65R and L74V/I in nucleoside combos. How can patients or doctors balance this fact with the potential lipoatrophy effects of AZT?

Again, a very interesting question. I think it is fair to say that any triple-NRTI drug regimen needs to include AZT to have a good chance of success, given the poor outcomes that have been associated with NRTI combinations such as tenofovir/abacavir/lamivudine or tenofovir/didanosine/lamivudine (very poor efficacy), or stavudine/didanosine/abacavir (poor efficacy and high toxicity) [reviewed in 1]. In these regimens, it appears that these drugs all tend to favor the emergence of a similar pattern of resistance mutations, so that there is very little barrier to the emergence of K65R or L74V/I. AZT appears to counteract this effect, as it “pulls in another direction,” actually becoming more potent when these resistance mutations start to emerge. This means that the virus has more difficulty becoming broadly resistant to both AZT and the other NRTI’s (most commonly lamivudine and abacavir) within the NRTI combination.

As stated above, I think the risk of lipoatrophy associated with AZT can be managed in a rational way that minimizes the chances of developing problematic fat loss, and in this particular case (when triple NRTI therapy is desired) there really is no effective alternative drug at present.

Do you think the move in international and U.S. guidelines for delayed treatment at lower CD4 counts will increase the incidence of lipodystrophy in the HIV population?

I think there is strong evidence that delaying treatment until CD4+ T cell counts fall below 200 increases the risk of a number of drug-related toxicities, including lipoatrophy (if using d4T or AZT) and neuropathy (which can be associated with HIV itself as well as the use of d4T or ddI) [reviewed in 2]. There is also a concern that low HDL-cholesterol levels associated with more advanced HIV disease may predispose patients to metabolic complications and the potential for a greater risk of cardiovascular disease [3]. I would argue that treatment should be initiated at higher CD4+ counts (i.e., 200–350) and should be focused on:

Assessing each individual case on its merits. This means taking into account the patient’s characteristics and finding the best “match” in terms of HIV therapy. These considerations may include the toxicity profiles of individual HIV drugs, as well as the tolerability of the HAART regimen. The main goal is to provide the best possible chance of achieving 100 percent adherence to therapy.
And, assessing and monitoring those side-effects that are specifically associated with the HIV drugs being used, so that these complications can be picked up early and managed appropriately.
The TARHEEL study results seem to point to the intriguing fact that even though mitochondrial DNA (mtDNA) levels rebounded after d4T therapy was discontinued, mitochondrial function did not recover. Do you think that there may be some permanent mitochondrial damage even after patients switch from d4T or AZT to non-thymidines?

I think the mitochondrial toxicity at a cellular level is reversible, as it is likely that the toxicity of these drugs is mediated specifically by their effects on mitochondrial DNA depletion. The more worrying problem is that severe lipoatrophy represents a profound loss of adipocytes (fat storing cells) within the fat tissue through cell death (apoptosis). The TARHEEL study showed very nicely that you can “turn off” this process of cell death by switching from d4T to a non-thymidine NRTI (i.e., far fewer cells are killed), but you are then left with the problem of having to replace the cells that have been lost. While the non-thymidine NRTI’s are obviously not toxic to fat tissue, they do not actively encourage new cells to grow, and treatments that may be anticipated to help this process of regeneration (such as rosiglitazone) have not performed well to date. This problem is further complicated by the fact that lipoatrophic fat tissue contains a large number of macrophages, inflammatory cells that are probably there to “mop up” the adipocytes and their stored fat after cell death, and these may also inhibit the growth and development of new fat cells.

What is your opinion about the use of micronutrients (carnitine, coenzyme Q-10, thiamine, riboflavin) or the use of uridine to reverse or prevent loss of mitochondrial DNA or function in the presence of thymidine analogs?

With regard to the micronutrients you mention, there is no evidence that they improve any clinical outcomes if used as a preventive treatment. They have been used in the management of lactic acidosis (usually in an intensive care setting) although, because these events are so rare, the benefits are not really known. Uridine treatment (in the form of a sugar cane extract called “Mitocnol” or “Nucleomaxx”) has shown a lot of promise as a preventive treatment that may limit the toxicity associated with either stavudine or zidovudine without compromising the effectiveness of these drugs against HIV, but these results have been obtained primarily from the laboratory. Clinical experience with this extract is minimal at present and the cost of treatment is about $100 per month. I’m sure more information will be available in the next year or so, which will be watched with interest.

We have seen several studies that show improvement in limb fat after switching patients from AZT or d4T to abacavir or tenofovir. Unfortunately, no one has really been able to quantify facial fat in those studies. Do you think that patients with moderate to severe facial wasting may see improvements after this switch? Some of your data show loss of fat cells due to macrophage activation. Do you think people may not have enough fat cells for facial lipoatrophy reversal?

This is an important area, but one where it has been difficult to obtain good data. Facial lipoatrophy is obviously one of the most stigmatizing aspects of lipodystrophy, and this is an area where people really want to see improvement following NRTI switching. We do see improved facial appearance associated with NRTI switching, although in general the more severe the initial lipoatrophy (prior to switching) the more limited the improvement. This is a frustrating aspect of the syndrome, as it is a case of “first affected, last to improve.” This means that less affected areas (such as the arms and trunk) tend to improve before more badly affected areas such as the face and legs. Also, because the process of “regrowing” populations of fat cells seems to be slow, improvements happen over years rather than months.

What is your personal opinion about the fact that AZT and d4T are still the most widely used drugs for the treatment of HIV in the developing world?

My own opinion is that we need to put this issue on the agenda and keep it there — particularly in the case of stavudine, where there is a substantial concern about toxicity issues. There is a rationale that stavudine may be better tolerated in non-white populations — and certainly this is an anecdotal opinion that is expressed by clinicians who look after mainly African-American patients. However, the potential toxicity of these drugs needs to be assessed carefully and quickly in the developing world, before the development of severe and widespread complications. We have already seen the burden of disease associated with severe lipoatrophy in our own communities — this history should not be reproduced in developing countries.

Besides lipoatrophy, what other long-term health implications does having decreased mitochondrial DNA or impaired function mean to someone with HIV?

In truth, probably very few implications. The effects of NRTI drugs on mitochondrial function appear to be very tissue-specific, so in the case of lipoatrophy it is very likely that the “damage” is limited specifically to fat tissue. For example, it is notable that stavudine treatment — which has been consistently associated with severe mitochondrial DNA depletion in adipocytes — has no significant effects on mitochondrial DNA in blood cells. Also, the mitochondrial toxicity associated with NRTIs appears to be readily reversible, in the sense that mitochondrial DNA depletion goes away quickly after ceasing/switching NRTI therapy.

Will we ever have data to show whether or not ddI is implicated in lipoatrophy?

Some historical data exists suggesting that ddI treatment is not associated with lipoatrophy. For example, an early study of dual NRTI therapy by Thierry Saint-Marc (published in 1999) included a number of patients receiving didanosine in both stavudine (d4T/ddI = 13/27, 48%) and zidovudine treatment groups (AZT/ddI = 13/16, 81%) that were well-matched for NRTI therapy duration. In this study, use of stavudine remained the most significant risk factor for lipoatrophy (relative risk 1.95 compared with zidovudine), while no significant didanosine effect could be demonstrated [4]. More recently, results from the FTC-301A study also suggest that the once-daily NRTI drug emtricitabine (FTC) compares favorably with stavudine (each combined with ddI-EC and efavirenz) in terms of lipoatrophy risk over 72 weeks (n=571), while maintaining equivalent efficacy and improved overall tolerability. Average loss of fat was noted only in the stavudine group, despite the fact that ddI was used in both study arms [5]. More long-term data are awaited in this study.

In your experience, does tenofovir have the same or different benefits when it comes to lipoatrophy reversal/prevention as abacavir? How about when it comes to lipids?

We have observed the same “non-toxic” effects on adipocyte’s mitochondrial DNA levels for these drugs, and the study data certainly suggest that tenofovir and abacavir are not associated with risk of lipoatrophy (both with an incidence of

Nelson chats at thebody.com about salvage

Transcript of The Body’s Live Chat With Nelson Vergel on Issues for HIVers With Multi-Drug Resistance

Following is the transcript of The Body’s live chat on issues for HIVers with multi-drug resistance, which took place on Feb. 16, 2005, at 9 p.m. Eastern Standard Time. The chat was sponsored by Roche and Trimeris, moderated by The Body’s editorial staff and hosted by Nelson Vergel, a leading treatment advocate who has been HIV positive since 1983. This transcript has been edited for grammar and clarity. In rare occurrences, additional follow-up information was obtained from the host after the chat’s conclusion.

This is the third chat that The Body has moderated; to see transcripts of previous chats, click here.

Moderator 1: Thank you all for coming to The Body’s live chat on HIV treatment issues for people with multi-drug resistance. Tonight’s topic is a broad one; our guest speaker, Nelson Vergel, will discuss HIV drug resistance, new drugs in development, health and nutrition tips, and other issues of importance for treatment-experienced HIVers.

Nelson, before you begin to answer everyone’s questions, would you like to tell the room a little bit about who you are and why you’re here tonight?

While we’re waiting for Nelson to introduce himself, you can read his full bio at: www.thebody.com/bios/vergel.html.

Nelson Vergel: I have been positive for 21 years. Formerly a chemical engineer, I have been active in the HIV field since 1988. I am a co-author of “Built to Survive” and lecture extensively around the country.

Moderator 1: Thanks, Nelson! And with that, let’s open the floor to everyone’s questions.

Original message from Confused: I have been on a HAART regimen that includes Kaletra [generic name: lopinavir/ritonavir] for a few years now, but have NOT had a treatment failure. For a number of reasons (liver toxicity, pill burden, etc.), I have been considering changing to Reyataz [generic name: atazanavir]. Everything I have read about Reyataz, however, lumps “people who have taken HIV drugs in the past” with “people who have experienced a drug failure.” To me those are two different issues. Thus, if I ultimately decide to switch, should I start the regimen of Reyataz boosted with Norvir [generic name: ritonavir] (for treatment-failure patients) or the once-a-day regimen without Norvir (for treatment-naive patients)? OR should I give up the idea entirely, since recent studies tend to suggest that Kaletra isn’t that much more toxic for the liver than Reyataz, and since conventional wisdom suggests that one shouldn’t change in mid stream?

Reply from Nelson Vergel: Please talk to your doctor about this. Kaletra is the protease inhibitor with the most long-term data. It has been shown to be effective in naive and experienced patients. Some people may experience lipid increases and diarrhea with it. It is taken twice a day. Reyataz is a newer protease inhibitor that is taken once a day, usually with Norvir as a booster. It can cause increases in bilirubin in some patients, making them jaundiced (turning their skin and eyes yellow). So far I have not seen studies that show any difference in liver enzyme increases between the two drugs. They seem to have comparable efficacy in a 48-week study. We do not know if that holds for longer periods of time.

Original message from Max: It would seem like many HIV specialists don’t know a lot about resistance. Is this your experience as well? Who should be sought?

Reply from Nelson Vergel: No. I think most HIV physicians who have large practices are pretty well trained in genotype and phenotype testing interpretation. But combining drugs and predicting response is still more of an art than a science in many cases.

Original message from MKNYC: How does one (or DOES one) try to assess in advance any kind of timeline for potentially developing resistance to regimens (assuming excellent adherence)?

Reply from Nelson Vergel: It is impossible to predict how durable a regimen will be, assuming that you are adhering perfectly to your medications.

Original message from Eduardo: Will the oral CCR5 inhibitors make Fuzeon [generic name: enfuvirtide; also known as T-20] obsolete since it is an injectable?

Reply from Nelson Vergel: Currently, there are several oral entry inhibitors in phase II development. They work on different receptors (entry ports) than Fuzeon. We are not sure if they will be effective in people with more advanced disease. Some of these drugs are being researched in combination with Fuzeon.

Moderator 1: For more info on entry inhibitors in development, you can also visit The Body’s collection of articles at: www.thebody.com/treat/fusion.html#other.

Original message from pozington_bear: I hear lots about the up-and-coming DAPYs, including TMC-120 and TMC-125, along with R278474. What do you think will come of them?

Reply from Nelson Vergel: I am very hopeful about these drugs. Tibotec is the first company in AIDS history that has two drugs going through the same phase of development. Both TMC-114 (a protease inhibitor) and TMC-125 (a non-nuke) have shown promising results for multi-drug resistance. They have just completed their phase II studies and are getting ready for phase III and expanded access in the upcoming months.

Original message from ATL650: My mother is resistant to all medications and the doctors say there is nothing else for her to do. Did she develop the resistance from not taking her medications as required? Is she really resistant? Will she be able to use the medicines after being off them for a couple of months, or is there nothing else she can do but wait to die?

Reply from Nelson Vergel: The only way to find out if your mother has indeed developed resistance to medications is to perform a genotype and/or phenotype test while she is on the meds. Her viral load has to be over 1,000 to be able to perform the test(s). There is conflicting data on whether it is a good thing or not to take a break from medications before starting a new regimen, but U.S. data shows that it may not be a good idea. Have her talk to her doctor about this.

Moderator 1: The Body’s “HIV Drug Resistance” page can also provide more info on the basics of resistance and resistance testing: www.thebody.com/treat/resistance.html.

Original message from MOD: With so many new agents in the pipeline, some of which will take a while, should one wait as long as possible before attempting to put together a new regimen?

Reply from Nelson Vergel: I am very hopeful about the new treatments. I have developed resistance to all medications myself and am waiting to access two active drugs in the future. Within the next year we will have access to six [new] drugs via phase III studies and expanded access programs. For those who need something right away and have developed resistance to most medications, Fuzeon and the new protease inhibitor, tipranavir, are good options to consider. Tipranavir is not FDA approved yet, but is available through expanded access.

Moderator 1: You can learn more about tipranavir’s Expanded Access Program at: www.atdn.org/access/ind/tipr.html.

Original message from Shay: Do you live a fairly busy, active full life?

Reply from Nelson Vergel: Yes. I lecture weekly around the country and moderate several Internet groups and Web sites. Keeping busy and having a purpose in life are the best medicines to stay alive.

Original message from clif: I have been through many drug regimens and am about to start yet another. I am going to be on six HIV meds: Sustiva [generic name: efavirenz], emtricitabine [brand name: Emtriva; also known as FTC], Fuzeon, ritonavir, stavudine [brand name: Zerit; also known as d4T] and tipranavir. Is it unusual to be on a combination of so many HIV meds? Also, I heard that there is a new, needleless injection system for Fuzeon using Bioject, which my pharmacy is being trained on now. Is this a viable option to the painful needle?

Reply from Nelson Vergel: Yes, it is usual for people with multi-drug resistance to take more than three drugs. Many times these combinations have not been studied. Yes, Roche is testing a needle-free device to see if people will have fewer injection site reactions. Contact your closest StatScript Pharmacy for details on how to join this phase IV study (go to www.statscript.com for their closest location).

Moderator 1: To add on to Nelson’s response, the brand name for the needle-free device is the Biojector; studies on using it with Fuzeon have just begun, though the device itself is already approved in the United States.

Original message from sissy: I was told I had AIDS in 1989 and have been on just about everything. I had two bad episodes of Stevens-Johnson Syndrome and my viral load recently doubled. I am about to try Lexiva [generic name: fosamprenavir], Fortovase [generic name: saquinavir] and Truvada [generic name: tenofovir/emtricitabine]. My CD4 count is 255 and my viral load is 48,800. I have NEVER been undetectable. I hate to change meds — I feel good on these. Any suggestions?

Reply from Nelson Vergel: Talk with your doctor about this. If you have not developed resistance to Lexiva, Fortovase and Truvada, it may be a good thing for you to start a regimen that will offer you maximum viral suppression.

Original message from justaguy: How did you get HIV?

Reply from Nelson Vergel: From man to man sex.

Original message from Max: Are you using Fuzeon now and how does it affect your lifestyle?

Reply from Nelson Vergel: Yes, I have been on Fuzeon for the past 18 months. It took me a while to get used to it since I travel so much. Fuzeon has stabilized my health. I have also been able to manage injection site reactions. Fuzeon is a drug that works if you have at least one more active agent to start with it.

Original message from sr90650: If your T-cell count stays above 400, are you still able to contract opportunistic infections? Also, how do you deal with the neuropathy in your feet?

Reply from Nelson Vergel: Most opportunistic infections occur at levels under 200 T cells. You can still get several HIV-related complications at 400 T cells, like thrush, neuropathy, lipodystrophy, wasting and many others.

The best way to deal with neuropathy is to avoid Zerit or ddC [generic name: zalcitabine; brand name: Hivid]. Some studies have shown that acetylcarnitine may improve pain and help with nerve regeneration. Some doctors prescribe tricyclic antidepressants and anticonvulsants to manage the pain. There is also data on the use of a red chili pepper gel that may work.

Original message from Joseph: How do you keep up your energy level?

Reply from Nelson Vergel: Fatigue is my main challenge. Exercise has helped me a lot. I must admit that I like coffee — a lot. Supplements like carnitine, co-enzyme Q10 and B vitamins also seem to help me. When I’m really run down and I have a lot to do, I take an attention deficit disorder drug like Adderall [a combination of the generic drugs dextroamphetamine and amphetamine]. Testosterone replacement has also helped me tremendously in the past 11 years. Getting enough sleep is extremely important. Talk with your doctor about all your options to deal with your fatigue.

Moderator 1: You can also learn more about fatigue at The Body (of course!) by visiting www.thebody.com/treat/fatigue.html#fatigue.

Original message from MikeR: Hello Nelson and thank you for doing this. My question: What options are open for someone who had no CD4 response to both T-20 and tipranavir taken together along with Reyataz, Viread [generic name: tenofovir], Videx [generic name: didanosine; also known as ddI], Epivir [generic name: lamivudine; also known as 3TC] and Norvir? I was told by the tipranavir study doctor that I was the “first non-responder” she had seen to that drug. What’s next?

Reply from Nelson Vergel: I know a few people like you. I am very hopeful that Tanox’s TNX-355, a once-a-week IV, Reverset [also known as D-D4FC], a new nucleoside, and other entry inhibitors will provide options for us in the next year or so when these drugs start their phase III studies and expanded access programs.

Original message from sam soriano: How do you reduce or eliminate injection site problems while using Fuzeon?

Reply from Nelson Vergel: I would suggest you join my Fuzeon support group by sending a blank e-mail to fuzeonsupport-subscribe@yahoogroups.com. I have injected Fuzeon in areas not recommended by the company and have managed to avoid my abdominal area, which seems to be the one that gives me the most trouble. Massaging for at least five minutes after the injections and using insulin syringes have also helped me a lot. Feel free to send questions to my support group. There are many people there that may help you. Also visit the Fuzeon resource center at TheBody.com.

Moderator 1: The Body’s main Fuzeon page is www.thebody.com/treat/t20.html; the Fusion Inhibitor Resource Center lives at www.thebody.com/fuzeon/resource/.

Original message from Confused: Do you have any specific suggestions for nutritional supplements?

Reply from Nelson Vergel: This is a very general question that will take me a long time to answer. I would suggest that you go to my Web site, medibolics.com, and click on the nutritional section. There is a link there that shows all the supplements I’m taking and why.

Original message from Hector: I have been fighting wasting ever since I was told by my doctor. He puts me on Serostim [a growth hormone] 6 mg every other day and only every other month and getting it from him is like pulling strings. Do you know of a doctor that treats wasting and HIV? I hate the way some of these doctors treat us HIVers. Please help me. I am in the HIV field as well. I don’t get hungry, I live alone [and am] very worried about myself.

Reply from Nelson Vergel: I do not know where you live, but I have a list of doctors on medibolics.com who use not only Serostim but anabolic steroids for men and women.

Moderator 1: The Body also has a collection of info on supplements at: www.thebody.com/treat/herbal.html.

Original message from Eduardo: Can you tell us where to apply for studies of new drugs and info on new drugs?

Reply from Nelson Vergel: The best Web sites to find out about studies for new drugs are:

salvagetherapies.org
clinicaltrials.gov
acria.org

Moderator 1: Also visit www.thebody.com/treat/open_trials.html for a comprehensive listing of clinical trial databases.

Original message from La Rae: If a drug is in Phase III, how long does it normally take to become available? Also, how long typically does it take to get from Phase II to Phase III?

Reply from Nelson Vergel: It depends. A drug that provides new options for people can go through accelerated approval. But usually a phase III may take 24-48 weeks. To go from phase II to phase III usually takes three to six months depending on the company. Phase II studies are meant to determine best dose and find out any side effects. Phase III are larger studies that are done prior to approval.

Moderator 1: New Mexico AIDS InfoNet has written a great overview of the U.S. drug approval process: www.thebody.com/nmai/approval.html.

Original message from poz88: Re-infection. Can two HIV/AIDS people have unprotected sex with each other and one becomes infected with a stronger strain of the virus? I manage several e-groups and several poz couples, and there seems to be varying opinion on this. I personally believe they CAN re-infect one another, but then I have had AIDS since ’88. What do I know?

Reply from Nelson Vergel: This is a very controversial subject and a gray area. All the superinfection reports that we have seen so far have been in people not taking HIV medications. We do not know if HIV medications may protect somebody from superinfection if they decide to have unprotected safe sex. I guess we will have to wait for more data.

Original message from ATL650: Nelson, I am so glad to hear you have been in great health for a long time. My question is do you consider yourself what is called a non-progressor?

Reply from Nelson Vergel: Not at all. If it wasn’t for the HIV medications I am taking, I would be dead. I would consider myself a normal progressor that for some reason has been able to survive for this long even though I have never had an undetectable viral load. I think that good nutrition, exercise, anabolics, stress management and keeping a positive attitude have been key to my survival.

Original message from wendy: What in the world can someone do if they get this multi-resistant HIV transmitted to them now?

Reply from Nelson Vergel: Oh boy, don’t get me started on this one. Nobody can really tell if the New York guy got a superbug or if his immune system was impaired before he got infected due to his crystal use. Around 14% of newly infected people nowadays are getting infected with HIV that is resistant to three of the approved drug classes.

Moderator 1: More info and opinions on this issue are available from our Web site at: www.thebody.com/treat/mdr_hiv.html.

Original message from lisa_89: I’ve been on HIV medication since diagnosed back in 1996. My T cells were around 360 and I’m not sure what my viral load was. I’ve been undetectable for years and had a T-cell count as high as 1,000; however, it hovers mostly around 850-900. My doctor says I’m doing excellent and we’ve been talking about taking a break from medication. I hear so much talk from friends and associates about how they’ve been doing off medication and the controversy about whether the cocktail works better than natural/alternative treatments that I’m confused and concerned about what to do next. Can you shed some light on this issue and help ease my mind about what I should do next?

Reply from Nelson Vergel: This is a very personal decision. There is conflicting data from structured treatment interruption studies. It seems that those with a low nadir (lowest T-cell count you ever had) may be more at risk for losing more T cells when taking a break from medications. Your nadir is not bad, however I would talk with your doctor about monitoring you closely if you decide to take a break from your HIV medications.

Original message from pablo: Did you ever experience any side effects such as facial wasting, buttocks wasting and potbelly? Can one do anything to combat these?

Reply from Nelson Vergel: I have experienced mild facial wasting that I treated 3 years ago in Tiajuana, Mexico with Bio-Alcamid. Now we have an FDA-approved drug in the United States called Sculptra [generic name: poly-L-lactic acid] that you can get for free if you make under $40,000 a year. Visit my Web site facialwasting.org for more information or join my list server by sending a blank e-mail to pozhealth-subscribe@yahoogroups.com.

I have managed buttock and body wasting with the use of anabolic steroids and exercise. More information about this is at medibolics.com.

Original message from texas: What are the top three supplements you think everyone with HIV should take?

Reply from Nelson Vergel: B-100 supplement, selenium and carnitine. It depends on the side effects that you may have. More information on supplements is at medibolics.com.

Original message from Robert: As a Dutch user of Fuzeon enrolled in the tipranavir trial, I would like to ask you: Besides the above-mentioned new medication, I also take loads of other HIV medications that give me some side effects. Since I started with Fuzeon and tipranavir, many more side effects have become apparent: a neurological condition called Restless Legs Syndrome, an overproduction of stomach juices and an alarmingly high cholesterol level. Is this because of these new medicines (I started taking them since about June of 2003) or is it just because my body cannot cope with yet another huge load of medicines? I am now taking meds to counterattack these side effects, but they in turn cause other effects, so I feel as if I am in some boring vicious circle. What is your opinion and how should I deal best with such a situation?

Reply from Nelson Vergel: So far I have not seen any reports on Restless Legs Syndrome being caused by antiretrovirals, but that does not mean that it may not happen. Tipranavir is well known to have gastrointestinal side effects and to increase lipids. If you have no more options to keep your viral load suppressed, I would try really hard to manage the side effects until new agents that may be more agreeable with you are available in a year or so through different studies.

Original message from Joe: I have been HIV+ for 15 years. My current regimen is Videx EC, Viramune [generic name: nevirapine] and Epzicom [generic name: abacavir/lamivudine]. My CD4 count is 236 and viral load 500. My doctor tells me that I am resistant to my drugs and wants me to switch to Fuzeon and a protease inhibitor, but I am very hesitant. I am 61 years old and have developed many health problems, such as high blood pressure, clogged arteries, PAD, COPD and depression, and I take medications for them. My CD4 count and viral load bounce back and forth. I would of course like to get a boost in my CD4 count and find something to stop the wasting, especially in the face. If I’m resistant to my drugs, why are they holding my numbers at a range I can live with? After all these years I feel if it ain’t broke don’t mess with it. But do you have any suggestions for an easier regimen?

Reply from Nelson Vergel: This is a very good question. Sometimes patients and doctors get very focused on keeping an undetectable viral load. Side effects and quality of life should also be considered when thinking about switching regimens. Some doctors are more conservative and try to keep you on the same combination if your health and numbers are stable. Ultimately, you are the one to make the decision. I would be concerned if I were you if your T cell count dropped below 200 and your viral load kept climbing.

Original message from Warren: I just recently completed drug trials on TMC-114 with no success. My virus has resistance to Fuzeon after nine months as well. Any suggestions?

Reply from Nelson Vergel: I do not know what your numbers are. You may want to wait if you can for future options that are coming up in the next few months. Go to salvagetherapies.org to explore your other options and talk to your doctor about treatment strategies.

Original message from NelsonFan: I just want to say, Nelson, that I admire your courage and commitment!

Reply from Nelson Vergel: Thanks a lot. You’re making me blush.

Original message from Reo: I have kidney failure and test positive for hepatitis C — I have been told by my doctor that my med options are limited. Right now I’m tolerating a Kaletra and Ziagen [generic name: abacavir] combo, but the bathroom routine is driving me crazy because I’m working full time. Being on dialysis, is there any combo I might consider? Sustiva kicked my butt.

Reply from Nelson Vergel: Talk to your doctor about this. There are other protease inhibitors, like Reyataz, that do not cause diarrhea. Try to avoid Viread and Videx, since they may present problems in those with pre-existing kidney disease.

Original message from pozington_bear: I have been on Fuzeon for almost three years. It was very successful at first, but I am now failing. I have been on tipranavir for about two years and have received no noticeable benefit. I just found out that I do not qualify for the CCR5 inhibitor trial because my virus uses mixed CCR5 and CXCR4 attachments. I have been positive for over 25 years. I am using or resistant to everything currently available. My viral load is 466,000. I have FOUR CD4s. What should I do next?

Reply from Nelson Vergel: I am sorry to hear that those combinations have failed you. I would keep my eye open for TMC-114, TMC-125, TNX-355, Reverset and other new agents coming soon. Go to salvagetherapies.org/newrx.html to see all the new drugs that are getting close to phase III. Talk to your doctor about keeping your replication capacity low with current HIV medications. Replication capacity measures how fast your virus multiplies and it is included in the phenotype test, Phenosense.

Moderator 1: You can also learn a little more about replication capacity by reading this article from Project Inform: www.thebody.com/pinf/nov04/replication.html.

Original message from wendy: Hi Nelson: How do you keep feeling so optimistic when you are really struggling to find treatment that works? Any tips you can share?

Reply from Nelson Vergel: Well, my T cells are still over 200 and my viral load is under 20,000, so I consider myself pretty stable. I am very fortunate to be very close to research data through my work at the drug development committee of the AIDS Treatment Activist Coalition (www.atac-usa.org). My activist work has given me a lot of hope about the future. We are looking for people who want to volunteer as treatment activists. We train people on how to become savvy about treatment information and how to deal with the pharmaceutical industry in different stages of research. In short, education and empowerment keep me optimistic.

Moderator 1: Tonight’s interactive chat on HIV treatment issues for people with multi-drug resistance has now concluded. Thank you, Nelson, for taking the time to answer all these questions — and thank you to everyone who asked questions or took the time to join our chat tonight!

My apologies to all of you who have submitted excellent questions we couldn’t get to tonight! I hope you’ll consider using The Body’s “Ask the Experts” area at www.thebody.com/experts.shtml to get the answers to your questions.

Nelson Vergel: I want to thank TheBody.com and the sponsors for this opportunity. Thanks to all of you for giving up your TV time to chat with me. I am looking forward to other chats in the future. Love and health to all.

Moderator 1: Thank you all again; enjoy the rest of your night!

Post-Chat Questions
These questions were submitted before or during the chat, but because of time limitations, Nelson did not have the chance to answer them.

Original message from alvy241: Are there going to be any fusion inhibitor drugs like Fuzeon in pill form in the near future (six months or less)?

Reply from Nelson Vergel: Currently, there are several companies developing CCR5 and CRX4 inhibitors that will be taken by mouth, but they will not be approved until 2007-2008. They will be available in probably six to 10 months in larger phase III studies and then in expanded access programs. Fuzeon acts on the gp41 protein of the virus, so it acts on a different site. Some of these companies are looking at combining Fuzeon with their inhibitors in the hope that there will be a stronger response. All of these oral inhibitors need to be taken with “optimized background therapy” (OBT) that may include the currently available drugs.

Original message from phillippe: Is Fuzeon a “last resort” drug?

Reply from Nelson Vergel: Well, that is what most of us used to think. But after looking at the data from Roche’s TORO studies (to review these studies, visit www.thebody.com/treat/t20_research.html), we have seen that those people who had over 100 T cells and a viral load of under 100,000 and who started a new drug with it had a better response. Also, those who started a combo without Fuzeon (the best possible combo as determined by genotype resistance testing and a patient’s medication history) and were switched to the Fuzeon arm (plus their regimen) later did not benefit from Fuzeon as much as those who had started it with one or more active drugs. So the message is to start Fuzeon when you can get the maximum response. Although, I have to admit, it is a big commitment for many people to begin an injectable drug. Personally, I decided to do whatever it takes to keep myself healthy, no matter how much discipline I needed to acquire to get there. I believe that HIV is a disease that really tests your level of commitment to your own health.

Original message from Max: I read in the newspaper the other day that one in four Fuzeon users drop it after the first month. Is this true, and if so, why? Because of pain? Because it’s not effective? Because it’s too tiresome to use?

Reply from Nelson Vergel: I am not sure that I have seen these data, but people probably drop out due to schedule conflicts that make it hard for them to mix and inject a drug twice a day, site reactions, fear of needles, or plain injection fatigue. It is definitely a commitment that some people may not be able to handle. I know flight attendants who have to inject in airplane bathrooms, so that shows you how committed some people are!

Original message from richardIII: Will site reactions no longer occur with the new Biojector device for T-20? That would be a godsend!

Reply from Nelson Vergel: So far the feedback I am getting at fuzeonsupport at yahoogroups.com is positive. We will have to wait and see until more people use the device to know if there are any interpersonal variations.

Original message from rfourniers: What’s the lowest your CD4 count has been?

Reply from Nelson Vergel: The lowest was 180, 10 years ago when I was only taking AZT plus 3TC.

Original message from La Rae: I have taken many drug combinations over the past 14 years. Now my strain is resistant to all drugs currently available. I am trying to get to Fuzeon and tipranavir, but I don’t even know if tipranavir will be effective. My doctor says that the test to determine whether I am resistant is not readily available. Can you suggest a process for me to get such a test?

Reply from Nelson Vergel: So far, I do not think that the currently available genotype tests include tipranavir. The maker of tipranavir thought that certain mutations might impair individual responses to the drug, but lately they have found that this is not the case. Tipranavir works pretty well when you start it with Fuzeon and possibly a background regimen that can lower your viral replication capacity. You may want to join my online support groups pozhealth or fuzeonsupport and ask others who may be on the combo already. You can do so by sending a blank e-mail to fuzeonsupport-subscribe@yahoogroups.com or to pozhealth-subscribe@yahoogroups.com.

Original message from Sam: Hi Nelson! Do you think that we’ll get to the point of having medicine regimens tailored to the individual instead of for general use? Seems that the medications would work better if the doctor had a DNA and genetic profile of the person being treated. Any comment?

Reply from Nelson Vergel: I certainly think treatments tailored to individuals would be more effective. We are finding out about genes that affect drug metabolism. Also, the use of therapeutic drug monitoring (testing for drug levels in your blood) will become more widely used in the United States. Roche got approval from the FDA in January for their first test that actually determines if individuals will be able to respond to certain drugs just by looking at their liver enzymes and metabolism. So I think that in about five to 10 years, we will have customized combos designed just for each individual.

Original message from Raffaele: I have recently read in The New York Times about an alleged vaccine, produced by a duo in Brazil, that is said to have been quite successful and is in phase II trials. Essentially it is purported to be administered once a year to an infected individual and assists the immune system in fighting HIV. I haven’t been able to discern more information or truths about it in recent days and my doctor hasn’t heard of it either … was it a bogus story?

Reply from Nelson Vergel: Actually I am very excited about this. The vaccine is made from a patient’s own dendritic cells and HIV isolated from the patient’s own blood. Dendritic cells are crucial to the immune response. They grab foreign bodies in the blood and present them to other immune cells to trigger powerful immune system responses to destroy the foreign invaders. It may be a costly option, but it sounds very promising for those of us who want to keep our immune systems from deteriorating. Please read more details at: www.thebody.com/kaiser/2004/nov30_04/hiv_vaccine.html.

Original message from La Rae: Is it possible to successfully apply for and get into phase III trials or expanded access programs in different parts of the country, regardless of where you live and what programs may be available in your immediate area? If so, how would one make such applications?

Reply from Nelson Vergel: For phase III studies, you have to be close to a research site (for a list, see www.salvagetherapies.org). For expanded access programs, it does not matter where you live, since your doctor can get the drug sent to his or her office. Right now there are close to eight phase II protocols and there may be four phase III protocols starting soon. Tipranavir is in expanded access.

Moderator 1: For more information about the program, healthcare professionals treating HIV-infected patients may obtain information by calling 1-888-524-8675 or visiting www.tpv-eap.com or www.clinicaltrials.gov. To find out particularly about tipranavir studies, click here.

Original message from MKNYC: Isn’t it true that 14% of those newly infected are resistant to three classes of HIV medications? And if so, then why are we just hearing about this one New York case as if it were something new?

Reply from Nelson Vergel: Yeah, about 14% of newly infected patients in a San Francisco cohort had resistance to three classes of drugs. But the alarming thing about the New York case is that the patient progressed to AIDS in two months instead of years. He got infected with a dual tropic virus that is more commonly found in later stages of HIV disease. He was also using crystal meth and had multiple sex partners. This, in combination with potential genetic factors, may have been responsible for his fast decline. He is being treated now with Fuzeon and Sustiva and his T cells are starting to increase. We will have to wait and see what happens in this case.

Original message from JDSmiami: How can you get Fuzeon if your state AIDS Drug Assistance Program (ADAP) doesn’t cover it?

Reply from Nelson Vergel: Most ADAP programs cover it. If not, you can contact Roche’s patient assistance program at:

Fuzeon Reimbursement Assistance Program; PO Box 221769; Charlotte, NC 28222; Phone: 866-487-8591; Fax: 866-487-8592.

Original message from George: Nelson, do you think that people like you and me, with lots of resistance, really have a chance to live 10 or more years?

Reply from Nelson Vergel: I am starting to believe so. I just came from the most important HIV research conference in the world and saw presentations on five new classes that are being studied in people. I think the key for most of us is how to buy time until we get there and how to stay healthy with failing drug regimens. I try to eat well, exercise, manage stress, take supplements, and take the best combo that can keep my viral replication capacity to a minimum (talk to your doctor about getting a replication capacity test). I think some of us may die, but many will make it to the day that there will be more than two new classes that will save our lives until a vaccine is developed. That is why I am so obsessed with getting the latest information, even before doctors see it. The next two to three years is a time of limbo for many of us, and we need to think positively and stay informed.

Original message from miamigo: My question has to do with staying on a regimen that is not working. Wouldn’t it make more sense to stop the regimen (because of toxicity) and just practice preventive measures to try and avoid opportunistic infections (my viral load is 750,000+ and CD4 below 20)?

Reply from Nelson Vergel: Taking a failing combo that your virus may have resistance to, assuming you can tolerate it, may still provide benefits. It can lower the speed at which the virus is replicating. So, the answer to your question is: Stay on drugs if you can, even if they are not working when it comes to keeping your viral load down and your T cells up. Just keep an eye on that replication capacity and try to start two new drugs together that you have sensitivity to.

Original message from JDSmiami: What do you think the hardest thing is about living with HIV?

Reply from Nelson Vergel: The hardest thing for me is the fear I have when I am sick. I always assume the worst and hate being sick. In 21 years of infection I have not learned how to be humble. I have a huge fear of depending on others for my care. That is what drives me to learn everything I can about my options, since doctors are too busy to tell us all of them, or they may not even know what’s coming up! Empower yourself and live!

My opinions about some HIV drugs

I wrote this for Test Positive Aware Network’s Positive Aware magazine, one of the best free HIV magazines in the country. Their link is http://www.tpan.com/

Sustiva

One of the “preferred drugs” in the DHHS guidelines due to its very good efficacy. It was the first drug to be approved for once-a-day dosing, so everyone jumped on it. Some people seem to get over the nightmares and fatigue in the first 2-3 weeks, but others seem not so lucky. Sustiva put a stop to my life for four months due to depression and fatigue, so I have my biases. But I have met many people who love it and are doing great on it. Also, unlike Viramune, Sustiva can increase lipids just like most protease inhibitors. I am waiting to see when BMS and Gilead will successfully co-formulate Truvada with Sustiva, since I think that will revolutionize the market with a convenient once-a-day pill to treat HIV with three meds. This will probably shift the paradigm in the industry to collaborate to improve patient adherence and pill burden. I just hope these two companies do the right thing and make that combo available to developing countries at low cost.—

KALETRA

Still the PI with the most robust long-term data and a “preferred” drug for treatment naïve patients. A tablet formulation of Kaletra was approved in the United States in October 2005. Abbott hopes to replace the original capsule formulation with the new tablets soon. The new formulation requires two fewer tablets a day and no refrigeration. The most common side effects of Kaletra in the past have been diarrhea and increases in cholesterol and triglycerides. Abbott claims that the new formulation may have fewer GI side effects but no improvements in triglycerides. The Kaletra market share is being eroded by Reyataz and may be further decreased with the introduction of TMC-114

FUZEON

This injectable product has had a difficult uptake in the community due to fear of needles, injection site reactions, and the fear that it is a “last resort drug before you die.” Studies have shown the obvious: starting Fuzeon with at least one more active agent may improve the duration of response. Unfortunately, most people who started it after approval did not have any other active agent left in their genotype, so they had to start it on top of a failing regimen, which only provided viral control for a few weeks. We have now seen the Aptivus RESIST and the TMC-114 POWER studies say the same thing: those who used these products with Fuzeon did better. I am happy to see that those who are running out of options can start Fuzeon with Aptivus or TMC-114, and possibly entry inhibitors soon. To minimize ISRs, people stopped using the needles provided in the kit and went for smaller insulin syringes. Also, a bioinjector needle-free device which is expected to be launched soon may help some people. Fuzeon is the most expensive single drug in the market at $26,000 a year (Aptivus plus Norvir is the highest boosted PI at $28,000). A very huge problem has been access for patients who do not have insurance in states with ADAP systems that have a cap on the number of people who can get Fuzeon. Roche would not give free drugs to those who apply after the cap has been met in those states.
Fuzeon is here to stay as a backbone to new drugs in the pipeline. But its price, administration and difficult access need to improve for it to be accepted as part of standard of care in the U.S.

REYATAZ

The new darling in the PI class. It is taken once a day, does not have food restrictions and has little effect on lipids. If you are taking antacids or PPIs, you need to talk to your doctor, since many of them are contraindicated with Reyataz. Also, many people have increases in bilirubin that may make them jaundiced. As an activist, I have been concerned about how BMS priced this expensive PI and how they have marketed this drug by implying it does not cause lipodystrophy. The price is the highest for a protease inhibitor and set the tone for all drugs approved later, so it was a terrible hit to publicly funded programs. Also, there is not a single study that proves that Reyataz does not cause lipodystrophy. Actually, Reyataz showed the same high incidence of lipodystrophy as Viracept (a well-known PI that can cause lipo). Just because this drug may not have the negative lipid effects caused by most PIs, it does not mean that it may not cause fat accumulation. If it was that easy, lipid lowering drugs could prevent or reverse lipo, and they have not shown to do that! I would love to see lipo data on Reyataz/Norvir + Truvada, a popular once a day combo that doctors prescribe hoping that it does not cause body changes. Reyataz is here to stay and growing stronger as more comparison data against Kaletra are generated

INVIRASE

Invirase is a protease that has been reformulated three times. I remember being in the first study in 1995 with high hopes. Unfortunately we found out later that very little of the drug got absorbed, so I developed PI resistance early. Roche reformulated it in capsules later for better absorption, but with greater pill burden and GI side effects. The latest formulation seems to be the friendliest of all, taken with Norvir boosting, with lower GI side effects and pill burden. Too bad Roche launched this last formulation with little exciting data for doctors to prescribe it, since the drug has been around for so long. I would love to see comparison data with Kaletra and Reyataz for efficacy and lipids. The new Invirase formulation could find its niche for those who have to stop Kaletra for GI and lipid side effects, or Reyataz for bilirubin. It is also important to see more solid data on double PI boosted combos for salvage patients

APTIVUS

The first protease inhibitor exclusively approved for patients who have developed PI resistance. Two 250 mg capsules of Aptivus plus two 100 mg capsules of Norvir should be taken with food twice a day. Like Norvir, it requires refrigeration. It can cause diarrhea, increased cholesterol and triglycerides, and liver problems. Close monitoring of liver enzymes is imperative with this drug. It works a lot better if started with another drug that shows up as active in your genotype test. Those taking Fuzeon with it had a better response than those who started Aptivus with drugs that they had resistance to. One big problem with Aptivus is that it does not play well with others, so the list of contraindicated drugs is long. Aptivus should never be taken with another protease inhibitor, since it decreases PI blood levels. Aptivus is a complicated drug, but I welcome its introduction in the market for a population that has few to no options left. Too bad it is the most expensive protease inhibitor, with an annual wholesale cost (with Norvir) of $28,840 as of October 2005. If you use it with Truvada and Fuzeon, the total annual wholesale cost jumps up to $66,000, an exorbitant amount for salvage therapy

LEXIVA

It was hard to say anything about Lexiva. It is a second generation Agenerase with fewer side effects and lower pill count. It has not gained the acceptance that Reyataz and Kaletra have gained in the market. It has interactions with Kaletra and Sustiva. I took it with Norvir for a few months, but had to stop it due to severe fatigue, a side effect not usually reported with this PI (we are all very different in how we respond to meds). But many people are taking it successfully and like its lower incidence of GI side effects and lipids. It can be used with or without Norvir. It can cause rash in some patients, especially if you are allergic to sulfa drugs, such as Bactrim

TMC 114 (NOT YET APPROVED AS OF APRIL 2006)

This new promising PI has not been approved yet but is available through expanded access for those with CD4 cells of 200 or under, and who have failed most drugs available in the market. So far, Phase II data look very good in those patients with multi-drug resistance. It seems to have most of the common PI-related side effects. The most commonly used dose will be 600 mg along with 100 mg of Norvir as a booster, both twice a day. I am looking forward to seeing more data of TMC-114 plus entry inhibitor combinations in salvage patients soon. Tibotec is also starting a combination study of its non-nuke TMC-125 plus TMC-114, a first in the HIV drug development world where two investigational agents are combined prior to approval. I applaud Tibotec for this courageous step, which will set the tone for future research studies encouraging Multi-Experimental Agent Trials (MEAT)

TRUVADA

This is one of the bestselling HIV drugs nowadays, and for many reasons. It is taken once a day, is durable, can treat hepatitis B, and does not cause lipoatrophy, neuropathy, and lipid problems. Many doctors are switching their patients from drugs that may cause lipoatrophy (d4T and AZT) to this drug since some studies show that lipoatrophy may improve slowly after that switch. But Viread is starting to worry some people when it comes to kidney dysfunction, especially in the older and more advanced patient population. Be very careful if you are still taking it with ddI, even at 250 mg of ddI (see ddI). Also, have your doctor calculate your creatinine clearance every three months just to make sure you are not developing early kidney disease. You can visit this web site for an easy calculation of your creatinine clearance: http://www.intmed.mcw.edu/clincalc/creatinine.html

VIRAMUNE

Viramune was the first non-nuke to be approved, and has proven to work as well as Sustiva, although some docs may not think it has the same “punch” as its competitor. It can cause a rash that can be treated without discontinuation. Viramune may have a higher incidence of symptomatic liver toxicity which consists of elevated liver enzymes plus at least one symptom, typically rash, but may include flu-like symptoms or fever. The severity of symptomatic liver toxicity ranges from mild symptoms with liver enzyme abnormalities to rapidly occurring liver failure and death. Studies have found that females have a three-fold higher risk of symptomatic Viramune liver toxicity than males, and females with CD4+ counts above 250 T-cells have a 12-fold higher risk of symptomatic liver toxicity than those with less. Males with CD4+ counts above 400 T-cells have a five-fold higher risk of symptomatic liver toxicity than those with less. Viramune has been found to prevent mother-to-child transmission in a single dose, although it needs to be used with nukes to prevent the easy emergence of HIV resistance. Because of its seeming lack of negative effects on the central nervous system, cholesterol, triglycerides, glucose, and possible lipodystrophy, Viramune is still a popular drug 10 years after approval. I would love to see studies looking at Viramune+Truvada and its effect on lipodystrophy and long term viral suppression. Many doctors are prescribing this combo without any research data backing it up

ZERIT

Zerit (d4T) has fallen out of grace after years of reports of lipoatrophy, neuropathy and higher lipids due to toxic effects on the cells’ mitochondria (energy factories of our cells). It was dropped from a “preferred drug” to an “alternate” one by the DHHS guidelines committee for the treatment of naïve patients. I just wish that they had done it sooner, since this fact has been known well since 2001. Unfortunately, Zerit is becoming one of the most commonly used drugs in the developing world. I feel horrible for people in countries like mine (Venezuela) who will endure these side effects even after we have learned so much in the developed world. Zerit is still a valuable drug in salvage therapy, when the benefits outweigh the risks. Some studies seem to indicate that lower-dose Zerit may work as well without as many side effects, but I do not think doctors are totally buying that concept

VIDEX- DDI

I have a lot of biases against this drug and get criticized for it sometimes. It is known to increase the chances of pancreatitis and neuropathy, and its role on lipoatrophy is not well known yet. The good thing is that it is a great nucleoside that can control HIV in a once-a-day dose. After years of being exposed to the ddI+d4T combo, many people developed facial wasting and general lipoatrophy, and irreversible neuropathy, so the DHHS guidelines panel prohibited its use in that combo. Too bad for those thousands of patients who were exposed to it. I have the strong feeling that we will soon see a ban on the ddI+Viread combo, even at lower ddI doses. This combo can increase the ddI blood levels too high in some, which can increase risk of pancreatitis. Kidney dysfunction due to potential intracellular interaction with Viread is also being observed. For some strange reason that no one can answer for me yet, many people I have met in the past year on that combo are also experiencing involuntary weight loss on ddI+Viread. Just make sure that you are taking a lower dose of 250 mg or below (depends on body weight) if you are taking ddI with Viread and that your T-cells and weight are not decreasing. We have a lot better nucleosides in the developed world now to not have to endure all the risks I have mentioned

AZT

I am one of the people who are still alive from the original high dose placebo-controlled AZT study in the late ‘80s and early ‘90s. In 1993 we were shocked and depressed after finding out that high dose AZT was killing us faster. Fortunately, we later found out that a lower dose would work well in combination with other meds. AZT is now available alone or in a combo of AZT + Epivir called Combivir. There is also a new generic version available that may be lower in price (we are waiting to see). It is one of the few drugs shown to penetrate the blood-brain barrier, so it may have some protective effects on neurological complications like dementia. Too bad it can cause anemia, muscle weakness, and fatigue in some, and now we are also learning that it may cause lipoatrophy. There are also some studies suggesting that AZT may have a “protective role” in preventing a key mutation, K65R, in all nuke regimens. This mutation may render most HIV resistant to several nucleosides

ZIAGEN

Another very effective nucleoside analog that has shown to be key to many backbones for NNRTIs and PIs. But it can cause a hypersensitivity reaction that can be lethal if not dealt with quickly. If you feel like you are coming down with the flu a few days after starting the drug, call your doctor immediately. This problem occurs in less than 10% of people. Ziagen is now gaining a lot more momentum after several studies showed that it may not cause lipoatrophy. I have my own biases about this drug, however. I experienced increased anxiety while on it. I am glad that a few reports came up in the literature about this problem after that, but it is something that has not been studied at all and that is ignored by doctors due to lack of information. Ziagen is available alone or in a combo with Epivir (Epzicom) or in a 3-drug combo with AZT and Epivir (Trizivir). Warning: Trizivir alone may not be effective to treat HIV in most patients. Also, do not take Epzicom plus Viread, since you may fail this regimen too quickly and develop resistance to most nucleosides

EPIVIR

We used to think this was a wimpy drug back a few years ago, since resistance to it is developed quite easily. But we have learned that virus resistant to 3TC seems to be weaker than ones that are not, so doctors still prescribe it even if you have resistance to it (the mutation is 184V). It does not seem to cause severe side effects, although some people have reported fatigue and changes in pigmentation in the palms of their hands. It can treat hepatitis B also. It is available alone or in combination with Ziagen (Epzicom) or AZT (Combivir) or in a three-drug combo with Ziagen + AZT (Trizivir). An interesting study showed that people who have to stop their meds due to toxicity but kept taking Epivir had a lower CD4 cell drop than those who stopped all drugs

I am so tired of price gauging in HIV!

AIDS Activists Cry Foul as Drug Companies Push Prices to Record LevelsPosted
Topic Health

The following was released by AIDS Treatment Activists Coalition:

A steady onslaught of “unreasonable, unacceptable, and unjustified” increases in the price of therapies to treat HIV has caused activists in the US to accuse drugmakers of artificially inflating the market at the expense of people living with HIV/AIDS. As an example, activists point to the recent launch of the new drug Aptivus, a protease inhibitor developed by Boehringer-Ingelheim, which came in at the highest price ever for this class of medication — more than $13,000 per year, which does not include the cost of other medications that must be taken in combination with Aptivus.

“We are approaching the point where a year’s worth of HIV medications in the US will cost anywhere from $30,000 to $50,000 a year. Every time a new medication is made available, it usually comes in at a new higher price than others in its class,” stated Nelson Vergel, a member of the AIDS Treatment Activists Coalition. “The same thing happened with Reyataz, another protease inhibitor made by Bristol-Myers Squibb. It was the first once-daily medication of this kind, and the company priced it at an all-time high, with regular increases since then. It now costs almost $11,000 per year. This behavior is simply unreasonable, unacceptable, and unjustified.”

Indeed, many healthcare and community groups question why there is no guidance for drug pricing based on type of medication or disease. In the US, prices charged for medications are often much higher than in other developed countries. This tends to work against patients, even those who have insurance. Howard Grossman, MD, Executive Director of the American Academy of HIV Medicine notes, “Many insurance companies have focused on the high price of drugs to treat HIV. Healthcare providers are finding their choices increasingly limited as higher-priced drugs are taken off ‘preferred’ lists, in some cases raising patient copays from $20 to $75 or more per prescription. Anything that prevents doctors from prescribing the properly-indicated drugs reduces our chance of controlling HIV. High prices are driving this.”
But privately insured patients aren’t the only ones suffering under this no-hold-barred system of pricing for life-saving and medically necessary medications. Public payer systems, such as the underfunded AIDS Drug Assistance Programs (ADAPs), provide medications for more than half of all patients with HIV/AIDS in the US. These programs must renegotiate prices regularly with drug companies, and steep increases in medication prices make it difficult to provide medication to the same number of people each year. With numbers of new infections increasing steadily and flat funding for ADAPs, medication waiting lists have developed in several states.

To make matters worse, new legislation forbids government negotiation with drug companies on prices. In other words, patients receiving government assistance for healthcare may not have access to new and better medications if excluded from formulary because of expense. Even if the medications are added, they will cause patients to meet individual spending caps even more quickly and will use up allotted budgets.

“Sadly, Boehringer-Ingelheim failed to realize that the size of the potential Aptivus market is directly tied to patients’ access through publicly funded programs, and they just made that market a lot smaller,” said Lei Chou, Director of Mobilization at the Community HIV/AIDS Mobilization Project (CHAMP). “State Medicaid Programs will delay coverage of the drug for months, AIDS Drug Assistance Programs will have to place access restrictions or may not cover it at all. This pricing decision will put Aptivus out of reach for the majority of patients who can benefit from it.”
As companies continue to create a system of haves and have-nots for people living with HIV/AIDS, activists plans to redouble their efforts against price-gouging and profiteering. By working with legislators, consumer protection groups, and other advocacy groups, AIDS activists envision a future where unbridled greed does not dictate what treatments patients can afford or how public resources are spent in the effort to keep people alive.

The AIDS Treatment Activists Coalition is a national coalition of AIDS activists, many living with HIV/AIDS, working together to end the AIDS epidemic by advancing research on HIV/AIDS.