Is the Answer to HIV-Associated Diarrhea Found in South America’s Rain Forest?
By Nelson Vergel, BsChE, MBA
As more and more shamans (traditional healers) in the Amazonian rain forest die as they age, the new generations of indigenous people are moving on to jobs in cities, forgetting valuable medicinal knowledge gathered through centuries. Recognizing this potential loss in key know-how a small team from a company called Shaman Pharmaceuticals in South San Francisco went searching for medicinal plants in South America’s rain forest by working hand-in-hand with local shamans. With the help of ethnobotanists and physicians who worked with the traditional healers to document the therapeutic qualities of the foliage, Shaman Pharmaceuticals created a library of 2,600 medicinal plants.
“Indigenous people led us to a situation where we could make and improve a safe and effective pharmaceutical product and give back to the population that provided the information," said Lisa Conte, founder of Shaman.
“We ensure that medicinal plants are cultivated with replanting that requires careful management and conservation in conjunction with the indigenous and local peoples who reside in the forest where it grows,” added Steven King, PhD, Vice President of Sustainable Supply, Ethnobotanical Research and Intellectual Property, one of the main experts involved in the search for medicinal plants in South America.
One of their earliest targets was Sangre de Drago ( “Dragon’s blood” or Croton lechleri), a plant with a blood-like sap (properly called ‘latex’) that has been used by indigenous people for centuries to treat wounds, diarrhea, stomach problems, and other ailments (Jones 2003.) Shaman’s researchers isolated and purified the main component from the latex, named “crofelemer”, and formulated crofelemer into standard oral medication. The company produced a supplement called “Normal Stool Formula” that was widely used in the HIV community in the 1990s to successfully treat diarrhea.
“It was our best seller for diarrhea,” said Fred Walters, founding director of the Houston Buyers Club, a Houston-based non profit that provides supplements at cost to people with HIV nationwide. “We were sad to see Shaman close its doors due to financial difficulties back then, so we are glad to see Napo Pharmaceuticals acquiring the rights for the pharmaceutical-grade of the product for new research and potential FDA approval,” added Mr. Walters.
“In our country and most other western countries, there are only two anti-diarrhea medications, both approved over 30 years ago and both work about the same way – they slow or stop the movement of the gut. Crofelemer works differently and we see an exciting opportunity to study crofelemer for HIV-associated diarrhea and many other diseases where diarrhea is a major, sometimes fatal symptom of other infections,” said David Golman, PharmD, Senior Director of Clinical Operations of Napo Pharmaceuticals. An estimate by the World Health Organization suggests that worldwide, everyday 6,800 children die from diarrhea and its complications (Guerrant 2002.) “Clearly, there is the need for a more effective and widely available treatment for diarrhea,” added Dr. Golman
Diarrhea associated with HIV infection is still very much an issue to many. In a survey performed by POZ magazine in September 2007 with a total of 941 responders, 21 % said that side effects were the primary reason that they switched antiretroviral regimens in the past. Diarrhea, nausea and vomiting were the number one side effects that make a person switch meds. In a recent prospective study of 163 HIV+ patients performed by Dr. Uzma Siddiqui, 28.2% of patients reported having 3 or more bowel movements per day but only 14.1% reported use of anti-diarrheal medications (about ½ of those with chronic diarrhea) (Siddiqui 2007).
Before the widespread availability of highly active antiretroviral therapy (HAART) in 1995, most HIV-infected people developed progressive immuno-supression and opportunistic infections (OIs); and many OIs were in the gastrointestinal track causing diarrhea. After the introduction of HAART, there was a dramatic decrease of OI-associated diarrhea, however, non-infectious causes appear to have become more dominant. In a review performed by Stephanie Call, MD (Call 2000) it was shown that between 1995 and 1997, while the use of HAART increased, non-infectious causes of diarrhea increased from 32% to 70%. One prominent cause of non-infectious diarrhea among HAART- treated patients is the antiretroviral medications themselves. Since their introduction in the market, we have learned that protease inhibitors like Viracept®, Norvir®, Kaletra®, Aptivus®, Lexiva®, Prezista®, and others can cause significant, even serious gastrointestinal problems in people taking those medications (Physicians Desk Reference 2008).
Another potential cause of HIV-associated diarrhea is the virus itself. In an interview for the newsletter HIVhealth, Calvin Cohen, MD, Research Director of the Community Research Initiative of New England, said that the HIV virus itself can increase the risk of diarrhea since HIV attacks the lymph nodes in the intestines. This may lead to a condition called enteropathy which can result in diarrhea and other diarrhea symptoms.
Currently, there are no drugs approved by the FDA for HIV-associated diarrhea in the U.S. but it remains a serious problem for many people. “Chronic diarrhea not only has a significant negative impact on quality of life, but it can also affect HIV treatment and adherence, decreasing the effectiveness of medications,” said Shannon Schrader, MD, a leading physician in Houston. “Diarrhea may also lead some of us to switch their patients to other HIV medications, reducing treatment options later on when the patient might need them more,” added Dr. Schrader.
“I have lived with HIV for over 15 years and deal with diarrhea weekly, even though my immune system has improved with HIV medicines,” said Al Benson, a patient and activist living in Los Angeles. “I am glad we have drugs like Imodium® and Lomotil®, but I am concerned that they give me a yo-yo effect from constipation to diarrhea returning with a vengeance. I certainly believe that we need another option that is more gentle on the gut,” added Mr. Benson.
Crofelemer is believed to work by a different mechanism of action. The common anti-diarrheal drugs such as Imodium® and Lomotil® are absorbed into the blood, distribute throughout the body, and work by slowing down the flow of material through the intestines, they are called “anti-motility” drugs. While this stops diarrhea, it also allows toxins to remain in the body longer. Crofelemer is thought to act locally in the gut, and because it is not absorbed the potential for systemic adverse drug effects and interactions are minimized. Crofelemer does not affect motility; instead it reduces the abnormal excessive flow of water into the gut that is the root cause of many diarrheas. In clinical studies crofelemer has been very well tolerated, and constipation in particular has not been commonly reported (Napo Pharmaceuticals, data on file).
“Crofelemer works by normalizing water flow in the gut. It is not absorbed into the blood, but acts in the intestines to treat diarrhea and reduce the chances for dehydration. Because it is not absorbed and acts locally, it has a favorable safety profile,” explained Pravin Chaturvedi, PhD, Chief Scientific Officer of Napo. The drug’s capacity to treat diarrhea by blocking the secretion of chloride ions, and still allowing bowel movements, makes this useful for treating chronic diarrhea,” explained Dr. Chaturvedi. “This is a novel mechanism of action for the treatment and management of diarrhea, and it has been brought to us by indigenous knowledge,” added Dr. Chaturvedi.
A study published in 2004 found that Viracept®, a commonly used protease inhibitor used to treat HIV, stimulated chloride ion secretion and may explain its high rates of diarrhea in HIV-positive patients (Rufo 2004). Crofelemer’s mechanism of action could provide an answer to drug induced secretory diarrhea.
Crofelemer has been tested in clinical studies involving approximately 1,700 patients with diarrhea of various causes. Its novel mechanism is important to people living with chronic diarrhea, so much so, that the U.S. Food and Drug Administration (FDA) granted Napo a fast-track designation for the crofelemer drug for use in treating HIV-related diarrhea (Napo Pharmaceuticals, data on file.) Napo is currently conducting a clinical study in HIV positive individuals with chronic diarrhea. More information can be found on the company’s web site (www.napopharma.com).
References:
Call, S. et al. The Changing Etiology of Chronic Diarrhea in HIV-infected Patients with CD4 Cell Counts Less Than 200 cells/cc. The American Journal of Gastroenterology 2000; Volume 95 (11): 3142-3146.
Guerrant, R. et al. Magnitude and Impact of Diarrheal Diseases. Archives of Medical Research 2002; Volume 33 (4): 351-355.
Jones, K. Review of Sangre de Drago (Croton lecheri)- A South American Tree Sap in the Treatment of Diarrhea, Inflammation, Insect Bites, Viral Infections, and Wounds: Traditional Uses to Clinical Research. The Journal of Alternative and Complementary Medicine 2003; Volume 9 (6); 877-896.
Rufo, PA. et al. Diarrhea-associated HIV-1 Aspartyl Protease-inhibitors Potentiate Muscarinic Cl- Secretion by T84 cells Via Prolongation of Cytosolic Ca2+ Signaling. Am J Physiol Cell Physiol 2004; Volume 286: 998-1008.
Siddiqui, U. et al. Prevalence and Impact of Diarrhea on Health-related Quality of Life in HIV-infected Patients in the Era of Highly Active Antiretroviral Therapy. Journal of Clinical Gastroenterology 2007; Volume 41 (5); 484-490.
-
The untold Side of the movie "Dallas Buyers Club"
The movie Dallas Buyers Club brings attention to a little-recognized part of the AIDS activist movement: ....
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Exhorbitant Price New Hepatitis C Drug
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Six Promising HIV Drugs in the Pipeline (2013-2014)
What new HIV medications do we have to look forward to over the next few years? How will these newer drugs improve upon the older ones? To shed some light on these questions....
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TheBodyPRO.com's Nelson Vergel sat down with leading HIV cure research activist Richard Jefferys for an update on current important aspects, and controversies, in HIV cure research....
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What Supplements Can I take with HIV medications?
Is it ok to supplement with Creatine (Cell-Tech), and Protein (Nitro-Tech) along with Glutamine...
Saturday, April 12, 2008
Can Facial/Buttock Wasting Reconstruction Costs be Deducted from US Income Taxes?
Someone was nice enough to do some research on this topic for me (from my list pozhealth at yahoogroups.com)
Hi Nelson,
To our friends in other countries - ignore this message! It's about US tax.
As is usual with tax, there's no simple yes/no answer to your question. My answer boils down to - it SHOULD be deductible, and it's worthwhile trying, but if you are audited, there's a good chance that it will be reversed and you will be billed for tax and interest, and possibly penalty.
Deductibility of medical expenses comes down to "medical necessity." Internal Revenue Code section 213(a) says this:
"There shall be allowed as a deduction the expenses paid during the taxable year, not compensated for by insurance or otherwise, for medical care of the taxpayer, his spouse, or a dependent ..., to the extent that such expenses exceed 7.5 percent of adjusted gross income."
In other words, you add up all your allowable medical expenses, and if they are more than 7.5% of your adjusted gross income (also called AGI - the last line of page 1 of your Form 1040), then the excess is allowed as an itemized deduction. If your AGI is $100,000, and your total medical expenses are $10,000, your itemized deduction will be $2,500. Your total itemized deductions have to exceed your "standard deduction" to get any benefit. The standard deduction for a single person in 2007 is $5,350.
By the way, as for medication, section 213(b) says "An amount paid during the taxable year for medicine or a drug shall be taken into account ... only if such medicine or drug is a prescribed drug or is insulin."
So, no deduction for aspiring or cough syrup.
Now, in the tax code, you always have to look for the definition of everything. Section 213(d)(1) says "The term 'medical care' means amounts paid for the diagnosis, cure, mitigation, treatment, or prevention of disease, or for the purposes of affecting any structure or function of the body ..." And then it goes on to also allow deductions for certain medical-related travel expenses, for long-term care, and for medical insurance premiums.
It sounds from the above like facial and buttock reconstruction would be covered - it mitigates disease (effect of the treatment of a disease, which amounts to the same thing), and does affect bodily structures.
However, section 163(d)(9) says "(A) The term 'medical care' does not include cosmetic surgery or other similar procedures, unless the surgery or procedure is necessary to ameliorate a deformity arising from, or directly related to, a congenital abnormality, a personal injury resulting from an accident or trauma, or disfiguring disease. (B) ... The term 'cosmetic surgery' means any procedure which is directed at improving the patient's appearance and does not meaningfully promote the proper function of the body or prevent or treat illness or disease."
We have two problems, then. First, anything that can ALSO be cosmetic, is very hard to prove as being medically necessary - it's the same reason we have trouble getting our insurance providers to cover the treatment. The IRS is extremely skeptical of such deductions. In addition, the IRS is very skeptical of any treatment that addresses a mental/emotional problem, as opposed to a physical problem. So if you have your butt fixed because it's painful to sit, that's a physical issue. If you have your face fixed because you can't even recognize yourself in the mirror and it throws you into a deep depression - the IRS may not be sympathetic.
This is a heavily-contested subject - not lipoatrophy treatment, but deduction of cosmetic treatment.
There is no requirement that treatment be provided in the US, and if you can show that it cost less because you had it done elsewhere, that may help, although it also may look to suspicious to examiner, particularly if it was done in a place that is also a vacation spot (hmmm, Baja Mexico, Brazil) ... and the regulations related to medical travel expenses mention that a "vacation for to improve general health" is not deductible so you'll need to be ready to defend against that.
The IRS has a publication on Medical Expenses called Publication 502. Here's what it says about cosmetic surgery:
"Generally, you cannot include in medical expenses the amount you pay for unnecessary cosmetic surgery. This includes any procedure that is directed at improving the patient's appearance and does not meaningfully promote the proper function of the body or prevent or treat illness or disease. You generally cannot include in medical expenses the amount you pay for procedures such as face lifts, hair transplants, hair removal (electrolysis), and liposuction.
"You can include in medical expenses the amount you pay for cosmetic surgery if it is necessary to improve a deformity arising from, or directly related to, a congenital abnormality, a personal injury resulting from an accident or trauma, or a disfiguring disease."
Here's the link to the on-line version of Publication 502: http://www.irs.gov/publications/p502/index.html
If you want to download it: http://www.irs.gov/pub/irs-pdf/p502.pdf
So, you need to be able to prove that you meet this definition. A letter from a doctor will be a necessity here. Discuss all this with your own tax provider. Large medical expenses are a red flag for audit, so if you have other stuff in your tax return you don't want them asking questions about, then you'll want to think twice about taking this deduction.
I hope this helps!
Someone was nice enough to do some research on this topic for me (from my list pozhealth at yahoogroups.com)
Hi Nelson,
To our friends in other countries - ignore this message! It's about US tax.
As is usual with tax, there's no simple yes/no answer to your question. My answer boils down to - it SHOULD be deductible, and it's worthwhile trying, but if you are audited, there's a good chance that it will be reversed and you will be billed for tax and interest, and possibly penalty.
Deductibility of medical expenses comes down to "medical necessity." Internal Revenue Code section 213(a) says this:
"There shall be allowed as a deduction the expenses paid during the taxable year, not compensated for by insurance or otherwise, for medical care of the taxpayer, his spouse, or a dependent ..., to the extent that such expenses exceed 7.5 percent of adjusted gross income."
In other words, you add up all your allowable medical expenses, and if they are more than 7.5% of your adjusted gross income (also called AGI - the last line of page 1 of your Form 1040), then the excess is allowed as an itemized deduction. If your AGI is $100,000, and your total medical expenses are $10,000, your itemized deduction will be $2,500. Your total itemized deductions have to exceed your "standard deduction" to get any benefit. The standard deduction for a single person in 2007 is $5,350.
By the way, as for medication, section 213(b) says "An amount paid during the taxable year for medicine or a drug shall be taken into account ... only if such medicine or drug is a prescribed drug or is insulin."
So, no deduction for aspiring or cough syrup.
Now, in the tax code, you always have to look for the definition of everything. Section 213(d)(1) says "The term 'medical care' means amounts paid for the diagnosis, cure, mitigation, treatment, or prevention of disease, or for the purposes of affecting any structure or function of the body ..." And then it goes on to also allow deductions for certain medical-related travel expenses, for long-term care, and for medical insurance premiums.
It sounds from the above like facial and buttock reconstruction would be covered - it mitigates disease (effect of the treatment of a disease, which amounts to the same thing), and does affect bodily structures.
However, section 163(d)(9) says "(A) The term 'medical care' does not include cosmetic surgery or other similar procedures, unless the surgery or procedure is necessary to ameliorate a deformity arising from, or directly related to, a congenital abnormality, a personal injury resulting from an accident or trauma, or disfiguring disease. (B) ... The term 'cosmetic surgery' means any procedure which is directed at improving the patient's appearance and does not meaningfully promote the proper function of the body or prevent or treat illness or disease."
We have two problems, then. First, anything that can ALSO be cosmetic, is very hard to prove as being medically necessary - it's the same reason we have trouble getting our insurance providers to cover the treatment. The IRS is extremely skeptical of such deductions. In addition, the IRS is very skeptical of any treatment that addresses a mental/emotional problem, as opposed to a physical problem. So if you have your butt fixed because it's painful to sit, that's a physical issue. If you have your face fixed because you can't even recognize yourself in the mirror and it throws you into a deep depression - the IRS may not be sympathetic.
This is a heavily-contested subject - not lipoatrophy treatment, but deduction of cosmetic treatment.
There is no requirement that treatment be provided in the US, and if you can show that it cost less because you had it done elsewhere, that may help, although it also may look to suspicious to examiner, particularly if it was done in a place that is also a vacation spot (hmmm, Baja Mexico, Brazil) ... and the regulations related to medical travel expenses mention that a "vacation for to improve general health" is not deductible so you'll need to be ready to defend against that.
The IRS has a publication on Medical Expenses called Publication 502. Here's what it says about cosmetic surgery:
"Generally, you cannot include in medical expenses the amount you pay for unnecessary cosmetic surgery. This includes any procedure that is directed at improving the patient's appearance and does not meaningfully promote the proper function of the body or prevent or treat illness or disease. You generally cannot include in medical expenses the amount you pay for procedures such as face lifts, hair transplants, hair removal (electrolysis), and liposuction.
"You can include in medical expenses the amount you pay for cosmetic surgery if it is necessary to improve a deformity arising from, or directly related to, a congenital abnormality, a personal injury resulting from an accident or trauma, or a disfiguring disease."
Here's the link to the on-line version of Publication 502: http://www.irs.gov/publications/p502/index.html
If you want to download it: http://www.irs.gov/pub/irs-pdf/p502.pdf
So, you need to be able to prove that you meet this definition. A letter from a doctor will be a necessity here. Discuss all this with your own tax provider. Large medical expenses are a red flag for audit, so if you have other stuff in your tax return you don't want them asking questions about, then you'll want to think twice about taking this deduction.
I hope this helps!
Wednesday, April 09, 2008
Living Positively With HIV
Lecture in Detroit , Michigan
Sponsored by the Midwest AIDS Prevention Pro ject (MAPP)
Practical Health Tips from a Long Term Survivor Expert
May 6th from 6:00 pm to 8:00 pm
Como’s Restaurant & Pizzeria
22812 Woodward Ave
Ferndale, MI 48220
Free dinner and a free raffle for an IPOD Shuffle
For reservations call MAPP at 248-545-1435
You must register to attend
Nelson Vergel
HIV positive survivor for two and a half decades, Nelson,
a key national leader in HIV treatment advocacy, is the
founder of the Program for Wellness Restoration (PoWeR),
the HIV non-profit agency. For more information about
Nelson’s work, visit www.powerusa.org.
Nelson has co-authored Built To Survive, the guide to living
healthily with HIV, founded the Body Positive Wellness
Center in Houston and has spoken to thousands of his peers
and medical professionals on HIV treatments, side effect
management, salvage therapies and quality of life issues.
Lecture in Detroit , Michigan
Sponsored by the Midwest AIDS Prevention Pro ject (MAPP)
Practical Health Tips from a Long Term Survivor Expert
May 6th from 6:00 pm to 8:00 pm
Como’s Restaurant & Pizzeria
22812 Woodward Ave
Ferndale, MI 48220
Free dinner and a free raffle for an IPOD Shuffle
For reservations call MAPP at 248-545-1435
You must register to attend
Nelson Vergel
HIV positive survivor for two and a half decades, Nelson,
a key national leader in HIV treatment advocacy, is the
founder of the Program for Wellness Restoration (PoWeR),
the HIV non-profit agency. For more information about
Nelson’s work, visit www.powerusa.org.
Nelson has co-authored Built To Survive, the guide to living
healthily with HIV, founded the Body Positive Wellness
Center in Houston and has spoken to thousands of his peers
and medical professionals on HIV treatments, side effect
management, salvage therapies and quality of life issues.
Committed to Living
Continuing Education Series
Nelson Vergel's Lecture in Chicago
Nationally known
Treatment advocate,AUTHOR,
Fitness&Nutrition guru
Wednesday May 7 , 2008
7-9pm
Location to be announced
Learn why exercise is so important in fighting HIV.
Learn fitness routines you can do at home.
Be prepared to get out of your seat and move around!
Funded by
Illinois Department of Public Health
Please RSVP to TPAN reception at
773-989-9400 by May 5
Continuing Education Series
Nelson Vergel's Lecture in Chicago
Nationally known
Treatment advocate,AUTHOR,
Fitness&Nutrition guru
Wednesday May 7 , 2008
7-9pm
Location to be announced
Learn why exercise is so important in fighting HIV.
Learn fitness routines you can do at home.
Be prepared to get out of your seat and move around!
Funded by
Illinois Department of Public Health
Please RSVP to TPAN reception at
773-989-9400 by May 5
Tuesday, April 08, 2008
PoWeR Releases Groundbreaking Lipodystrophy Resources for HIV-Positive People
CONTACT: Nelson Vergel, Director
powertx@aol.com
713-539-1978
Houston, April 8, 2008- Program for Wellness Restoration, PoWeR, released the results of the largest online patient surveys performed to date on lipodystrophy options and resources along with a free Spanish translation of their book :"Built to Survive". The 776- people survey summarizes the main therapeutic options used in the HIV community along with a list and ratings of providers who specialize in reconstructive procedures for HIV-related body changes.
Ten years have passed since the first report of lipodystrophy at an HIV conference. The excitement and hope for a longer life that accompanied the arrival of Highly Active Anti-Retroviral Therapy (HAART) has been tempered by accounts of humps, bellies, and facial wasting. A decade on, many unanswered questions and misconceptions about HIV associated lipodystrophy persist with only a limited number of treatment options available. Frustrated and tired of waiting for answers from the medical community, many people living with lipodystrophy have turned to the internet for advice, treatment and support in hopes of reversing some of the devastating effects of this stigmatizing syndrome.
Lipodystrophy is a condition of abnormal fat redistribution that can lead to either lipohypertrophy (fat accumulation in specific areas of the body such as the neck, belly, upper torso, and breasts) or lipoatrophy (fat loss in the face, buttocks, arms and legs).
"I am very happy that we have been able to provide this key information to the HIV community", said Nelson Vergel, founding director of PoWeR. "People have been wanting this important health resource for 10 years after the first report of lipodystrophy was reported at an HIV conference", added Vergel.
The results of the survey can be found at: Survey Results
A list of providers with comments from patients can be found at : Survey Results
A free PDF (Adobe Acrobat Reader format) copy of the Spanish translation of the book Built to Survive can be downloaded from : http://powerusa.org/pdf/Fortaleceteysobrevive1.pdf
Another distressing and negleted issue related to HIV lipodystrophy is wasting of the buttocks. Currently, there is no research being performed in the US or abroad on this debilitating problem that can cause pain and discomfort in patients who have to sit down for extended periods of time at work or school. PoWeR gathered all available anecdotal and research information on the subject and made it available in their new web page: http://facialwasting.org/buttock_wasting.htm
PoWeR is a national non -profit all-volunteer organization that provides patient-friendly educational information to HIV-positive people and their clinicians about ways to improve HIV treatment response, side effects, and quality of life. More information can be found at www.powerusa.org
For an update on where we are after ten years of lipodystrophy, please visit http://thebody.com/content/toparts/art45454.html
CONTACT: Nelson Vergel, Director
powertx@aol.com
713-539-1978
Houston, April 8, 2008- Program for Wellness Restoration, PoWeR, released the results of the largest online patient surveys performed to date on lipodystrophy options and resources along with a free Spanish translation of their book :"Built to Survive". The 776- people survey summarizes the main therapeutic options used in the HIV community along with a list and ratings of providers who specialize in reconstructive procedures for HIV-related body changes.
Ten years have passed since the first report of lipodystrophy at an HIV conference. The excitement and hope for a longer life that accompanied the arrival of Highly Active Anti-Retroviral Therapy (HAART) has been tempered by accounts of humps, bellies, and facial wasting. A decade on, many unanswered questions and misconceptions about HIV associated lipodystrophy persist with only a limited number of treatment options available. Frustrated and tired of waiting for answers from the medical community, many people living with lipodystrophy have turned to the internet for advice, treatment and support in hopes of reversing some of the devastating effects of this stigmatizing syndrome.
Lipodystrophy is a condition of abnormal fat redistribution that can lead to either lipohypertrophy (fat accumulation in specific areas of the body such as the neck, belly, upper torso, and breasts) or lipoatrophy (fat loss in the face, buttocks, arms and legs).
"I am very happy that we have been able to provide this key information to the HIV community", said Nelson Vergel, founding director of PoWeR. "People have been wanting this important health resource for 10 years after the first report of lipodystrophy was reported at an HIV conference", added Vergel.
The results of the survey can be found at: Survey Results
A list of providers with comments from patients can be found at : Survey Results
A free PDF (Adobe Acrobat Reader format) copy of the Spanish translation of the book Built to Survive can be downloaded from : http://powerusa.org/pdf/Fortaleceteysobrevive1.pdf
Another distressing and negleted issue related to HIV lipodystrophy is wasting of the buttocks. Currently, there is no research being performed in the US or abroad on this debilitating problem that can cause pain and discomfort in patients who have to sit down for extended periods of time at work or school. PoWeR gathered all available anecdotal and research information on the subject and made it available in their new web page: http://facialwasting.org/buttock_wasting.htm
PoWeR is a national non -profit all-volunteer organization that provides patient-friendly educational information to HIV-positive people and their clinicians about ways to improve HIV treatment response, side effects, and quality of life. More information can be found at www.powerusa.org
For an update on where we are after ten years of lipodystrophy, please visit http://thebody.com/content/toparts/art45454.html
Monday, March 31, 2008
FDA Probes Heart Risk From 2 HIV Drugs
FDA Probes Heart Risk From 2 HIV Drugs
FDA Reviewing Heart Attack Data in HIV Patients Taking Ziagen and Videx
March 28, 2008 -- The FDA is reviewing data on heart attack risk in HIV
patients taking the anti-HIV drugs Ziagen and Videx.
The FDA's review centers on the Data Collection on Adverse Events of Anti
HIV Drugs (D:A:D) study, which includes more than 33,000 HIV patients in North
America, Europe, and Australia.
The D:A:D study is tracking short-term and long-term adverse events of
treatment with anti-HIV drugs.
According to the FDA, analyses of D:A:D data gathered through Feb. 1, 2007,
show that recent use of Ziagen or Videx was associated with an increased risk
of heart attack. "Recent use" refers to current use of the drugs or
using the drugs within the past six months.
"Patients taking either of these drugs had a greater chance of
developing a heart attack than patients taking other medications," states
the FDA. "The risk did not appear to increase over time, but remained
stable and appeared to be reversible after [Ziagen] or [Videx] were
stopped."
Heart attack risk appeared to be greater in patients who had other heart
disease risk factors, including smoking, older age, high cholesterol, high
blood pressure, diabetes, and a history of heart disease.
The FDA considers those analyses to be incomplete. Because the FDA's review
isn't finished, the FDA isn't telling anyone to stop using or prescribing
Ziagen and Videx. At this point, the FDA advises patients and doctors to weigh
the risks and benefits of each HIV drug they use, including Ziagen and
Videx.
Drug Companies Respond
Ziagen is made by GlaxoSmithKline.
In a news release, GlaxoSmithKline states that its analyses show no
increased risk of heart attack associated with Ziagen and that no biological
mechanism linking Ziagen treatment to heart attacks has been identified.
GlaxoSmithKline advises patients not to discontinue treatment on their own,
and to minimize modifiable cardiovascular risk factors such as high blood
pressure, high cholesterol, diabetes, and smoking.
"Although the D:A:D study data suggest a relative risk increase in heart
attack risk for patients who are starting or continuing [Ziagen], that risk
remains low in absolute terms, and therefore [Ziagen] remains an important
treatment option for those patients," states a GlaxoSmithKline news
release.
Videx is made by Bristol-Myers Squibb.
"We have not seen an increase in cardiovascular events in prior studies
of Videx or in our safety database," Bristol-Myers Squibb spokeswoman Sonia
Choi tells WebMD.
Tuesday, March 25, 2008
HIV Cruise Raises $6000 for HIV causes
The HIV Cruise Retreat : A Fun Source of Education and Funds for HIV Projects
CONTACT: Paul Stalbaum at Paul@universal-travel.com
800-735-0401 ext 241
Fort Lauderdale, March 21, 2008- A group of 225 HIV positive men and women went sailing away from the worries of the disease while obtaining key health information and raising funds for HIV non profit projects. In this 10th year, the retreat raised $6,000 for Doctor’s Without Borders. Over $30,000.00 has been raised over the past 10 years.
“It is great to have people who have been challenged for years with fears of death enjoy life in the company of others who are on the same boat as they are”, said Nelson Vergel, AIDS activist and lecturer on the cruise. “I am glad our project leader Paul Stalbaum has been able to make this possible for so many people to spend a week sailing the seas at affordable prices while they get key medical information and bond with others” added Vergel.
“As a doctor who treats hundreds of HIV patients, I must say that spending a week with so many people having fun while being helped with medical information is an ideal scenario”, said Dr Michael Wohlfieler, a leading South Florida HIV physician and featured speaker on the cruise.
Sam, a long term survivor from San Francisco and participant of last year’s cruise said: “We remember all too well when the virus was considered more or less a signal that it was time to get one’s affairs in order. Thankfully those days are behind us. A week like the one I had on this cruise reminds me that life is rich and full and when the good times roll it can be downright amazing”. “I will definitely not miss this year’s cruise!” added Sam.
“This year’s cruise promises to be even better with a very exciting itinerary sailing over Halloween from Ft Lauderdale with stops at Grand Turk (Turks and Caicos), St Maarten, St Thomas and Princess Cays”, said cruise organizer Paul Stalbaum. “We will actually have separate fun activities for gay and straight groups with some intermingling ” added Stalbaum.
For more information please call Paul at 800-735-0401 ext 241 or visit his two web sites: http://www.hivcruise.com/ for the gay group and http://www.positivecruise.com/ for the heterosexual group.
Thursday, March 20, 2008
HIV Lipodystrophy: Where are we after 10 years?
From Gay Men's Health Crisis
HIV Lipodystrophy: Where Are We After Ten Years?
By Nelson Vergel
July-December 2007
Note: The following article expresses the opinions and learned lessons of the writer, not of GMHC, Treatment Issues, or their staff. It is not intended as medical advice and should not be taken as such.
Ten years have passed since the first report of lipodystrophy at an HIV conference. The excitement and hope for a longer life that accompanied the arrival of Highly Active Anti-Retroviral Therapy (HAART) has been tempered by accounts of humps, bellies, and facial wasting. A decade on, many unanswered questions and misconceptions about HIV associated lipodystrophy persist with only a limited number of treatment options available. Frustrated and tired of waiting for answers from the medical community, many people living with lipodystrophy have turned to the internet for advice, treatment and support in hopes of reversing some of the devastating effects of this stigmatizing syndrome.
Lipodystrophy is a condition of abnormal fat redistribution that can lead to either lipohypertrophy (fat accumulation in specific areas of the body such as the neck, belly, upper torso, and breasts) or lipoatrophy (fat loss in the face, buttocks, arms and legs). An online survey of 695 people (predominantly white men, over the age of 40, living with HIV for over 10 years and with exposure to HAART for at least that long) found that 20% had considered suicide because of body shape changes associated with lipodystrophy. Almost 90% of respondents believed that their HIV medications caused lipodystrophy, and 20% had stopped taking their HIV medications altogether due to this concern. Further, over 60% of respondents reported being rejected by potential sexual partners because of the syndrome. A similar number of respondents indicated that they had stopped looking into the mirror because of crippling body dissatisfaction. Nearly all of the respondents attempted to curb the effects of lipodystrophy with diet and exercise or by using costly facial reconstruction procedures, supplements and hormones -- treatments not typically covered by insurance companies or drug assistance programs.
Lipoatrophy and HIV Medications
In 1999, the HIV drug Zerit was correlated with the development of lipoatrophy related fat loss under the skin.1 Since then, several studies have concluded that Zerit can affect the way our mitochondria (energy factories in our cells) work and multiply. Later studies also linked lipoatrophy to AZT, although at a lower rate than Zerit. Nucleoside reverse transcriptase inhibitors (NRTIs) like Zerit and AZT, keep HIV from altering the genetic material of healthy T-cells, thereby halting the reproduction of new virus cells. Additionally, NRTIs affect the mitochondria in fat cells under the skin, preventing them from multiplying and causing them to die. Also, those who have taken Zerit and Videx (another NRTI) together report more lipoatrophy than those taking Zerit alone. This combination is not recommended by guideline groups. It appears that Zerit and AZT make fat accumulation worse in the presence of protease inhibitors or non-nucleoside analogs (NNRTIs) like Sustiva, leading researchers to suspect that their negative effect may play a combined role. However, Sustiva taken with Viread (Tenofovir) and Epivir (3TC) seems to cause less lipoatrophy. Due to the high risk of developing lipoatrophy and neuropathy, the US Department of Health and Human Services guidelines committee dropped Zerit from the list of recommended drugs for first line therapy for people new to HAART.
Viread (Tenofovir) and Ziagen (Abacavir), two other NRTIs in the same drug class as Zerit and AZT, do not seem to strongly correlate with the development of lipoatrophy. Some people have even reported a slow reversal of the fat loss after switching from Zerit or AZT to either Ziagen or Viread. However, even after a number of years most patients do not experience re-accumulation of fat in their faces after going off AZT or Zerit. It is also important to note that puzzling new data from a recent study by the AIDS Clinical Trials Group2 showed that 20% of subcutaneous fat loss (loss in body fat closer to the skin's surface) occurred in a small percentage of patients starting HAART for the first time with a combination of Sustiva, Viread and Epivir. More studies are needed to determine why lipoatrophy still occurs in some patients in the absence of Zerit or AZT.
The sales of Zerit and AZT in the industrialized world have dropped considerably in the past years due to their effects on lipoatrophy. Unfortunately, these two drugs are among the primary HIV medications used in the developing world, so millions of people in poorer countries will continue to suffer with body changes.
Treatment Options for Lipoatrophy
In recent years many men have relied on an off-label injectable anabolic steroid called nandrolone decanoate (old trade name: Deca Durabolin), to "balance out" their bodies and add muscle to their thin extremities and buttocks affected by lipoatrophy. Even though Watson Laboratories ceased production of nandrolone in March of 2007, it is still available through prescription at compounding pharmacies for a low cost.3
Uridine (Nucleomaxx), a supplement made of sugar cane and available through a German supplier,4 may lessen lipoatrophy in patients taking Zerit, however it may also cause abdominal fat and high triglycerides. These side effects, along with high cost and bad taste, make Uridine an unpopular choice. However, for those who must take Zerit, Uridine may be a viable option to prevent or reverse lipoatrophy. Additionally, for those who are no longer taking Zerit, the diabetes drug Rosiglitazone (Avandia) works well for reversing lipoatrophy. There are side effects however, including weight gain and high triglycerides.
Since 2002 there have been a couple of non-permanent reconstruction procedures available to treat facial lipoatrophy. The face wasting reconstruction option, Sculptra (polylactic acid, old name: NewFill) entails an expensive series of multiple sessions, requiring additional touch ups that can be used to treat those moderately affected by lipoatrophy. Radiesse, another FDA approved option, seems to last a little bit longer but is also costly, requiring 3?5 sessions and yearly touch ups. Some patients treated with face wasting fillers experience side effects such as bruising and treatable granulomas (hardened pimple-like nodules). There are patient assistance programs available for both Sculptra and Radiesse.5
There are no FDA approved permanent solutions for facial lipoatrophy, yet many in the US seek tiny injections of silicone (Silikon 1000) from their doctors. Silikon 1000 can be used legally in an off-label manner for facial lipoatrophy. Silikon 1000 micro-injections can reconstruct patients' faces slowly over five sessions spaced one month apart. There is no patient assistance program for this option and sessions cost anywhere from $600 to $900. Here too, multiple sessions are required. Beware that very few US doctors are well trained in this procedure.
Another permanent product, Polymethylmethacrylate (PMMA), has been used in Brazil for eight years and in Mexico for three with relatively positive results, though more time is needed to determine the long term effects of this procedure. Usually 2?4 sessions are required and no yearly touch ups are needed. Short term, we have seen that PMMA can harden and be lumpy in certain patients, but many people seem pleased with the results. Artefill, a PMMA based product, is FDA approved for cosmetic purposes but not for HIV related lipoatrophy. Artefill is extremely expensive for the amount required to treat lipoatrophy, so some HIV positive people in the US go to Mexico or Brazil for the procedure, where costs can range from $2000 to $6000. PMMA is not removable.
BioAlcamid (poly-alkylamide gel), also permanent, is an injectable filler unavailable in the US (some patients travel to Mexico or Canada for injections). Unfortunately, BioAlcamid forms a "pocket" in the face and buttocks enabling bacteria to penetrate and posing a high risk of infection. As such, extreme caution is warranted before pursuing this option.
It is critical to remember that no long-term data on these experimental facial reconstruction treatments are available, so one must weigh the risks of injecting a foreign substance into one's body. Sadly, many people find that the emotional, psychological and social toll of living with lipoatrophy is so great as to justify these risks.
Understanding LipohypertrophyUnlike lipoatrophy, researchers have not been able to attribute lipohypertrophy (fat gain in the belly, back of neck and breasts) to any specific medication or drug class. Protease inhibitors were once thought to be the main culprits. However, researchers have recently discovered that fat gain in the belly may relate to inflammatory responses in the immune system when CD4 cells increase in number. This means that those who start HAART with a lower baseline CD4 count may see greater lipodystrophy. Moreover, recent data shows that patients with a CD4 count of over 250, who start a HAART regime with protease inhibitors boosted with Norvir plus Viread and Epivir, do not experience a gain in visceral fat (fat surrounding the internal organs). It is still too early to tell what happens to those on this particular regimen who start with lower CD4 counts. Some studies have shown that those who begin taking protease inhibitors in combination with Zerit, AZT or Zerit plus Videx seem to have more visceral and hump fat gain than those who start on protease inhibitors with other drugs. It may be that the same drugs that are linked to lipoatrophy may also make fat gain worse, especially in patients who start HAART with fewer CD4 cells.
A common misconception promoted by a few pharmaceutical companies and echoed by some doctors is that HIV medications that do not increase cholesterol, and that triglycerides do not cause fat gain. On the contrary, several studies have shown that people taking lipid friendly drugs like Reyataz with Viread also gain fat in the belly after starting HAART.
Dr. David Nolan, a clinician and researcher at Royal Perth Hospital in Western Australia and an expert on fat metabolism and HIV, was asked about why visceral fat does not get "burned off" by Zerit and AZT like subcutaneous fat does. Dr. Nolan hypothesized that fat cells in the organ cavity may not be as susceptible as subcutaneous fat cells to the mitochondrial toxicity caused by Zerit and AZT.
Fat gain may also be linked to insulin resistance. Insulin resistance can cause glucose intolerance, which has been associated with fat gain, increased triglycerides, and the development of diabetes. Insulin is a hormone produced by the pancreas to control blood sugar-glucose. HIV medications may block or slow down the process by which insulin converts glucose to energy. In laboratory studies, Crixivan and higher doses of Norvir and Zerit have been shown to impair the action of insulin in fat and muscle cells. In this scenario the pancreas will tend to produce more and more insulin to compensate for the decrease in function. High insulin levels may be present for years before type 2 diabetes develops. A glucose tolerance test (GTT) may reveal that problem easily but it is hardly used in clinical practices. Additionally, some people may have a genetic predisposition to insulin resistance. A sedentary lifestyle and a diet rich in sugars and animal fats may also compound this problem. In any case, insulin resistance may just be a part of the mystery of lipohypertrophy. There is no agreement among researchers whether or not monitoring insulin levels in HIV-positive people is justifiable or dependable as a tool to assess insulin resistance and fat gain.
The full body dual x-ray absorptiometry (DEXA) scan is the gold standard test in lipodystrophy. It is a highly valuable test that can provide information about body fat, muscle mass and bone density (low bone density has been associated with HIV in several studies.) Both Medicare and private insurance often cover this inexpensive test. While the scan cannot differentiate between fat accumulated in the belly on under the skin in the abdominal area, it can be useful as a baseline to assess body changes and to justify reimbursable therapies for fat, muscle, and bone mass.
Treatment Interventions for Lipohypertrophy
Some people have switched from protease inhibitors to Viramune or Sustiva to combat visceral fat gain, but this has not been shown to make a difference. It is not yet known what happens to belly fat when a patient switches from Zerit or AZT to Viread or Ziagen while taking protease inhibitors or non-nucleoside analogs like Sustiva or Viramune.
The recombinant human growth hormone Serostim is a daily injectable drug approved by the FDA for HIV associated wasting. At approximately $3000 a month, it is an expensive option for treating lipodystrophy. Serostim works well in lowering abdominal fat but has many side effects including joint pain, water retention, carpal tunnel syndrome, and irreversible diabetes. These side effects and the lack of proven long-term health benefits are why the FDA has not approved Serostim for the treatment of HIV related fat accumulation. Tesamorelin-TH9507, made by Theratecnologies, is a daily injectable growth hormone precursor that is in its last stages of FDA approval. Tesamorelin appears to have fewer side effects than Serostim, but may take a longer time to show benefits in patients. Disappointingly, fat gain returns after discontinuation of both Serostim and Tesamorelin.
Leptin, a hormone that produced by fat cells, is another new contender in the search to decrease visceral fat. Researchers have found that leptin levels in the blood are proportional to an individual's level of body fat. Leptin works in the part of the brain that controls appetite and other basic functions. High levels of leptin generally suppress the appetite and stimulate the burning of fat. Leptin does not appear to have a negative impact on glucose tolerance.
Nowadays, physicians are likely to prescribe testosterone gels, injections, and subcutaneous pellets. A testosterone gel applied to the belly can reduce the waist size in HIV-positive men. This decrease is usually as a result of a reduction in subcutaneous fat, not in visceral fat. In contrast, a small pilot study of Oxandrin (an oral anabolic steroid) has yielded encouraging results in decreasing visceral fat. Increases in the low density lipoprotein (the "bad" cholesterol) and decreases in the high density lipoprotein (the "good" cholesterol) correspond to a small decrease in subcutaneous fat. There are no data yet on a connection with the popular anabolic steroid, nandrolone decanoate, and visceral fat reductions.
Some individuals who have been looking elsewhere for fat burners have fallen prey to advertisements pushing growth hormone supplements or fat burners. These products do little but increase blood pressure and anxiety and are generally considered scams.
Metformin (trade name, Glucophage), is a generic diabetes drug that has been shown to improve glucose tolerance and lower visceral fat. Its effects may be enhanced by exercise. Metformin improves insulin sensitivity, triglycerides and fatty liver but can also cause diarrhea and weight loss. There have also been reports of low blood sugar and dizzy spells associated with this drug.
In addition to the aforementioned treatments many patients explore liposuction. Ultrasound-assisted liposuction can be used to successfully remove fat accumulated in buffalo humps and around the neck.
Some patients complain about the enlargement of salivary glands on each side of the face commonly referred to as the "chipmunk look." While only a few radiologists know how to use it for this purpose, low dose electron radiation has worked very effectively in treating the enlargement of salivary parotid glands. It is unknown whether the "chipmunk look" is related to lipodystrophy or caused by immune reconstitution.
Another under explored intervention is diet and exercise. A study at Tufts University revealed a trend towards less lipodystrophy in those who had higher consumption of soluble fiber (fruits and vegetables) and who exercised. However more research is needed with the use of diets lower in simple carbohydrates. These diets have been shown to improve insulin resistance and visceral fat in non-HIV studies. One observational cohort showed that people with HIV eat more saturated fats. A small pilot on a combination of cardiovascular and resistance exercise showed decreased triglycerides and visceral fat. However, adherence to exercise remains a challenge to many people, and exercise research in HIV generally remains in its infancy.
Increased Lipids: Low Density Lipoprotein (LDL) and Triglycerides
The most common lipid abnormalities in HIV are high triglycerides and LDL, "bad" cholesterol, and low High Density Lipoprotein (HDL), "good" cholesterol. Before HIV-positive people start HIV medication for the first time, both their high and low density lipoprotein may be lower than normal. However, after HIV drugs are started, low and high density lipoproteins and triglycerides increase in some people. Some studies have shown that LDL increases to "pre-HIV" levels while HDL never returns to normal levels. Increased triglycerides is the most strongly associated lipid change caused by HIV medications such as protease inhibitors, Zerit, AZT, or Sustiva. Among protease inhibitors, Reyataz seems to correlate with the lowest lipid increases.
Many people want to start supplements before they start lipid lowering medications. The only supplements with solid emerging data on lipids are omega-3 fatty acids (fish oils), and niacin (also available as Niaspan). Fish oils can decrease triglycerides but some patients' stomachs cannot tolerate them. Niacin is better than any lipid lowering drug in increasing the "good" cholesterol (HDL). It can cause flushing of the face and a hot sensation for a half an hour at a time, but most people get used to it. Non-flush versions are available but their effectiveness is unknown.
It is not clear if Raltegravir (Isentress, the first integrase inhibitor) or Maraviroc (Celsentry -- a CCR5 entry inhibitor) have any effect on body composition. So far, they appear to be lipid friendly when taken with Viread and Epivir. Fuzeon (an injectable entry inhibitor) also seems to be lipid friendly, but it is usually used with boosted protease inhibitors that can cause increases in lipids. It seems that there may be genetic factors that make some patients more prone to increased low density lipoprotein (bad) cholesterol and triglycerides.
Lipid lowering agents like statins (Lipitor, etc) or fibrates (Tricor, etc.) can work wonders in many, but even with their use, some patients never reach "normal" lipid levels. A combination of niacin, lower sugar and animal fat intake, exercise, fish oil supplements or an increase in fatty cold water fish consumption (salmon) and soluble fiber (fruits, vegetables, oats) are sometimes used to treat lipids. Some individuals have tried combining statins and fibrates, but this combo can lead to an increase in muscle related disorders in some patients.
Conclusion
We have learned a lot during the past 10 years about body changes associated with HIV, but many more questions remain. It is the hope that those new to HAART therapy will not have to suffer the devastating drug side effects that their predecessors have had to contend with in the past 20 years. As patients, it is our responsibility to stay educated and learn from others about emerging options that may make it possible one day to live fully without HIV related body changes and other side effects.
For more information visit: http://www.facialwasting.org/ or to subscribe to the largest internet HIV health discussion group send a blank email to pozhealth-subscribe@yahoogroups.com
Nelson Vergel is director of Program for Wellness Restoration.
A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. AIDS. 1999 Sep 10;13(13):1659-67.
Metabolic Outcomes of ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI-, and NNRTI-sparing Regimens for Initial Treatment of HIV-1 Infection. Richard H. Haubrich, S Riddler, G DiRienzo et al.
More information is available at http://www.medibolics.com/.
More information is available at http://www.nucleomaxx.com/.
More information is available at http://www.facialwasting.org/.
HIV Lipodystrophy: Where Are We After Ten Years?
By Nelson Vergel
July-December 2007
Note: The following article expresses the opinions and learned lessons of the writer, not of GMHC, Treatment Issues, or their staff. It is not intended as medical advice and should not be taken as such.
Ten years have passed since the first report of lipodystrophy at an HIV conference. The excitement and hope for a longer life that accompanied the arrival of Highly Active Anti-Retroviral Therapy (HAART) has been tempered by accounts of humps, bellies, and facial wasting. A decade on, many unanswered questions and misconceptions about HIV associated lipodystrophy persist with only a limited number of treatment options available. Frustrated and tired of waiting for answers from the medical community, many people living with lipodystrophy have turned to the internet for advice, treatment and support in hopes of reversing some of the devastating effects of this stigmatizing syndrome.
Lipodystrophy is a condition of abnormal fat redistribution that can lead to either lipohypertrophy (fat accumulation in specific areas of the body such as the neck, belly, upper torso, and breasts) or lipoatrophy (fat loss in the face, buttocks, arms and legs). An online survey of 695 people (predominantly white men, over the age of 40, living with HIV for over 10 years and with exposure to HAART for at least that long) found that 20% had considered suicide because of body shape changes associated with lipodystrophy. Almost 90% of respondents believed that their HIV medications caused lipodystrophy, and 20% had stopped taking their HIV medications altogether due to this concern. Further, over 60% of respondents reported being rejected by potential sexual partners because of the syndrome. A similar number of respondents indicated that they had stopped looking into the mirror because of crippling body dissatisfaction. Nearly all of the respondents attempted to curb the effects of lipodystrophy with diet and exercise or by using costly facial reconstruction procedures, supplements and hormones -- treatments not typically covered by insurance companies or drug assistance programs.
Lipoatrophy and HIV Medications
In 1999, the HIV drug Zerit was correlated with the development of lipoatrophy related fat loss under the skin.1 Since then, several studies have concluded that Zerit can affect the way our mitochondria (energy factories in our cells) work and multiply. Later studies also linked lipoatrophy to AZT, although at a lower rate than Zerit. Nucleoside reverse transcriptase inhibitors (NRTIs) like Zerit and AZT, keep HIV from altering the genetic material of healthy T-cells, thereby halting the reproduction of new virus cells. Additionally, NRTIs affect the mitochondria in fat cells under the skin, preventing them from multiplying and causing them to die. Also, those who have taken Zerit and Videx (another NRTI) together report more lipoatrophy than those taking Zerit alone. This combination is not recommended by guideline groups. It appears that Zerit and AZT make fat accumulation worse in the presence of protease inhibitors or non-nucleoside analogs (NNRTIs) like Sustiva, leading researchers to suspect that their negative effect may play a combined role. However, Sustiva taken with Viread (Tenofovir) and Epivir (3TC) seems to cause less lipoatrophy. Due to the high risk of developing lipoatrophy and neuropathy, the US Department of Health and Human Services guidelines committee dropped Zerit from the list of recommended drugs for first line therapy for people new to HAART.
Viread (Tenofovir) and Ziagen (Abacavir), two other NRTIs in the same drug class as Zerit and AZT, do not seem to strongly correlate with the development of lipoatrophy. Some people have even reported a slow reversal of the fat loss after switching from Zerit or AZT to either Ziagen or Viread. However, even after a number of years most patients do not experience re-accumulation of fat in their faces after going off AZT or Zerit. It is also important to note that puzzling new data from a recent study by the AIDS Clinical Trials Group2 showed that 20% of subcutaneous fat loss (loss in body fat closer to the skin's surface) occurred in a small percentage of patients starting HAART for the first time with a combination of Sustiva, Viread and Epivir. More studies are needed to determine why lipoatrophy still occurs in some patients in the absence of Zerit or AZT.
The sales of Zerit and AZT in the industrialized world have dropped considerably in the past years due to their effects on lipoatrophy. Unfortunately, these two drugs are among the primary HIV medications used in the developing world, so millions of people in poorer countries will continue to suffer with body changes.
Treatment Options for Lipoatrophy
In recent years many men have relied on an off-label injectable anabolic steroid called nandrolone decanoate (old trade name: Deca Durabolin), to "balance out" their bodies and add muscle to their thin extremities and buttocks affected by lipoatrophy. Even though Watson Laboratories ceased production of nandrolone in March of 2007, it is still available through prescription at compounding pharmacies for a low cost.3
Uridine (Nucleomaxx), a supplement made of sugar cane and available through a German supplier,4 may lessen lipoatrophy in patients taking Zerit, however it may also cause abdominal fat and high triglycerides. These side effects, along with high cost and bad taste, make Uridine an unpopular choice. However, for those who must take Zerit, Uridine may be a viable option to prevent or reverse lipoatrophy. Additionally, for those who are no longer taking Zerit, the diabetes drug Rosiglitazone (Avandia) works well for reversing lipoatrophy. There are side effects however, including weight gain and high triglycerides.
Since 2002 there have been a couple of non-permanent reconstruction procedures available to treat facial lipoatrophy. The face wasting reconstruction option, Sculptra (polylactic acid, old name: NewFill) entails an expensive series of multiple sessions, requiring additional touch ups that can be used to treat those moderately affected by lipoatrophy. Radiesse, another FDA approved option, seems to last a little bit longer but is also costly, requiring 3?5 sessions and yearly touch ups. Some patients treated with face wasting fillers experience side effects such as bruising and treatable granulomas (hardened pimple-like nodules). There are patient assistance programs available for both Sculptra and Radiesse.5
There are no FDA approved permanent solutions for facial lipoatrophy, yet many in the US seek tiny injections of silicone (Silikon 1000) from their doctors. Silikon 1000 can be used legally in an off-label manner for facial lipoatrophy. Silikon 1000 micro-injections can reconstruct patients' faces slowly over five sessions spaced one month apart. There is no patient assistance program for this option and sessions cost anywhere from $600 to $900. Here too, multiple sessions are required. Beware that very few US doctors are well trained in this procedure.
Another permanent product, Polymethylmethacrylate (PMMA), has been used in Brazil for eight years and in Mexico for three with relatively positive results, though more time is needed to determine the long term effects of this procedure. Usually 2?4 sessions are required and no yearly touch ups are needed. Short term, we have seen that PMMA can harden and be lumpy in certain patients, but many people seem pleased with the results. Artefill, a PMMA based product, is FDA approved for cosmetic purposes but not for HIV related lipoatrophy. Artefill is extremely expensive for the amount required to treat lipoatrophy, so some HIV positive people in the US go to Mexico or Brazil for the procedure, where costs can range from $2000 to $6000. PMMA is not removable.
BioAlcamid (poly-alkylamide gel), also permanent, is an injectable filler unavailable in the US (some patients travel to Mexico or Canada for injections). Unfortunately, BioAlcamid forms a "pocket" in the face and buttocks enabling bacteria to penetrate and posing a high risk of infection. As such, extreme caution is warranted before pursuing this option.
It is critical to remember that no long-term data on these experimental facial reconstruction treatments are available, so one must weigh the risks of injecting a foreign substance into one's body. Sadly, many people find that the emotional, psychological and social toll of living with lipoatrophy is so great as to justify these risks.
Understanding LipohypertrophyUnlike lipoatrophy, researchers have not been able to attribute lipohypertrophy (fat gain in the belly, back of neck and breasts) to any specific medication or drug class. Protease inhibitors were once thought to be the main culprits. However, researchers have recently discovered that fat gain in the belly may relate to inflammatory responses in the immune system when CD4 cells increase in number. This means that those who start HAART with a lower baseline CD4 count may see greater lipodystrophy. Moreover, recent data shows that patients with a CD4 count of over 250, who start a HAART regime with protease inhibitors boosted with Norvir plus Viread and Epivir, do not experience a gain in visceral fat (fat surrounding the internal organs). It is still too early to tell what happens to those on this particular regimen who start with lower CD4 counts. Some studies have shown that those who begin taking protease inhibitors in combination with Zerit, AZT or Zerit plus Videx seem to have more visceral and hump fat gain than those who start on protease inhibitors with other drugs. It may be that the same drugs that are linked to lipoatrophy may also make fat gain worse, especially in patients who start HAART with fewer CD4 cells.
A common misconception promoted by a few pharmaceutical companies and echoed by some doctors is that HIV medications that do not increase cholesterol, and that triglycerides do not cause fat gain. On the contrary, several studies have shown that people taking lipid friendly drugs like Reyataz with Viread also gain fat in the belly after starting HAART.
Dr. David Nolan, a clinician and researcher at Royal Perth Hospital in Western Australia and an expert on fat metabolism and HIV, was asked about why visceral fat does not get "burned off" by Zerit and AZT like subcutaneous fat does. Dr. Nolan hypothesized that fat cells in the organ cavity may not be as susceptible as subcutaneous fat cells to the mitochondrial toxicity caused by Zerit and AZT.
Fat gain may also be linked to insulin resistance. Insulin resistance can cause glucose intolerance, which has been associated with fat gain, increased triglycerides, and the development of diabetes. Insulin is a hormone produced by the pancreas to control blood sugar-glucose. HIV medications may block or slow down the process by which insulin converts glucose to energy. In laboratory studies, Crixivan and higher doses of Norvir and Zerit have been shown to impair the action of insulin in fat and muscle cells. In this scenario the pancreas will tend to produce more and more insulin to compensate for the decrease in function. High insulin levels may be present for years before type 2 diabetes develops. A glucose tolerance test (GTT) may reveal that problem easily but it is hardly used in clinical practices. Additionally, some people may have a genetic predisposition to insulin resistance. A sedentary lifestyle and a diet rich in sugars and animal fats may also compound this problem. In any case, insulin resistance may just be a part of the mystery of lipohypertrophy. There is no agreement among researchers whether or not monitoring insulin levels in HIV-positive people is justifiable or dependable as a tool to assess insulin resistance and fat gain.
The full body dual x-ray absorptiometry (DEXA) scan is the gold standard test in lipodystrophy. It is a highly valuable test that can provide information about body fat, muscle mass and bone density (low bone density has been associated with HIV in several studies.) Both Medicare and private insurance often cover this inexpensive test. While the scan cannot differentiate between fat accumulated in the belly on under the skin in the abdominal area, it can be useful as a baseline to assess body changes and to justify reimbursable therapies for fat, muscle, and bone mass.
Treatment Interventions for Lipohypertrophy
Some people have switched from protease inhibitors to Viramune or Sustiva to combat visceral fat gain, but this has not been shown to make a difference. It is not yet known what happens to belly fat when a patient switches from Zerit or AZT to Viread or Ziagen while taking protease inhibitors or non-nucleoside analogs like Sustiva or Viramune.
The recombinant human growth hormone Serostim is a daily injectable drug approved by the FDA for HIV associated wasting. At approximately $3000 a month, it is an expensive option for treating lipodystrophy. Serostim works well in lowering abdominal fat but has many side effects including joint pain, water retention, carpal tunnel syndrome, and irreversible diabetes. These side effects and the lack of proven long-term health benefits are why the FDA has not approved Serostim for the treatment of HIV related fat accumulation. Tesamorelin-TH9507, made by Theratecnologies, is a daily injectable growth hormone precursor that is in its last stages of FDA approval. Tesamorelin appears to have fewer side effects than Serostim, but may take a longer time to show benefits in patients. Disappointingly, fat gain returns after discontinuation of both Serostim and Tesamorelin.
Leptin, a hormone that produced by fat cells, is another new contender in the search to decrease visceral fat. Researchers have found that leptin levels in the blood are proportional to an individual's level of body fat. Leptin works in the part of the brain that controls appetite and other basic functions. High levels of leptin generally suppress the appetite and stimulate the burning of fat. Leptin does not appear to have a negative impact on glucose tolerance.
Nowadays, physicians are likely to prescribe testosterone gels, injections, and subcutaneous pellets. A testosterone gel applied to the belly can reduce the waist size in HIV-positive men. This decrease is usually as a result of a reduction in subcutaneous fat, not in visceral fat. In contrast, a small pilot study of Oxandrin (an oral anabolic steroid) has yielded encouraging results in decreasing visceral fat. Increases in the low density lipoprotein (the "bad" cholesterol) and decreases in the high density lipoprotein (the "good" cholesterol) correspond to a small decrease in subcutaneous fat. There are no data yet on a connection with the popular anabolic steroid, nandrolone decanoate, and visceral fat reductions.
Some individuals who have been looking elsewhere for fat burners have fallen prey to advertisements pushing growth hormone supplements or fat burners. These products do little but increase blood pressure and anxiety and are generally considered scams.
Metformin (trade name, Glucophage), is a generic diabetes drug that has been shown to improve glucose tolerance and lower visceral fat. Its effects may be enhanced by exercise. Metformin improves insulin sensitivity, triglycerides and fatty liver but can also cause diarrhea and weight loss. There have also been reports of low blood sugar and dizzy spells associated with this drug.
In addition to the aforementioned treatments many patients explore liposuction. Ultrasound-assisted liposuction can be used to successfully remove fat accumulated in buffalo humps and around the neck.
Some patients complain about the enlargement of salivary glands on each side of the face commonly referred to as the "chipmunk look." While only a few radiologists know how to use it for this purpose, low dose electron radiation has worked very effectively in treating the enlargement of salivary parotid glands. It is unknown whether the "chipmunk look" is related to lipodystrophy or caused by immune reconstitution.
Another under explored intervention is diet and exercise. A study at Tufts University revealed a trend towards less lipodystrophy in those who had higher consumption of soluble fiber (fruits and vegetables) and who exercised. However more research is needed with the use of diets lower in simple carbohydrates. These diets have been shown to improve insulin resistance and visceral fat in non-HIV studies. One observational cohort showed that people with HIV eat more saturated fats. A small pilot on a combination of cardiovascular and resistance exercise showed decreased triglycerides and visceral fat. However, adherence to exercise remains a challenge to many people, and exercise research in HIV generally remains in its infancy.
Increased Lipids: Low Density Lipoprotein (LDL) and Triglycerides
The most common lipid abnormalities in HIV are high triglycerides and LDL, "bad" cholesterol, and low High Density Lipoprotein (HDL), "good" cholesterol. Before HIV-positive people start HIV medication for the first time, both their high and low density lipoprotein may be lower than normal. However, after HIV drugs are started, low and high density lipoproteins and triglycerides increase in some people. Some studies have shown that LDL increases to "pre-HIV" levels while HDL never returns to normal levels. Increased triglycerides is the most strongly associated lipid change caused by HIV medications such as protease inhibitors, Zerit, AZT, or Sustiva. Among protease inhibitors, Reyataz seems to correlate with the lowest lipid increases.
Many people want to start supplements before they start lipid lowering medications. The only supplements with solid emerging data on lipids are omega-3 fatty acids (fish oils), and niacin (also available as Niaspan). Fish oils can decrease triglycerides but some patients' stomachs cannot tolerate them. Niacin is better than any lipid lowering drug in increasing the "good" cholesterol (HDL). It can cause flushing of the face and a hot sensation for a half an hour at a time, but most people get used to it. Non-flush versions are available but their effectiveness is unknown.
It is not clear if Raltegravir (Isentress, the first integrase inhibitor) or Maraviroc (Celsentry -- a CCR5 entry inhibitor) have any effect on body composition. So far, they appear to be lipid friendly when taken with Viread and Epivir. Fuzeon (an injectable entry inhibitor) also seems to be lipid friendly, but it is usually used with boosted protease inhibitors that can cause increases in lipids. It seems that there may be genetic factors that make some patients more prone to increased low density lipoprotein (bad) cholesterol and triglycerides.
Lipid lowering agents like statins (Lipitor, etc) or fibrates (Tricor, etc.) can work wonders in many, but even with their use, some patients never reach "normal" lipid levels. A combination of niacin, lower sugar and animal fat intake, exercise, fish oil supplements or an increase in fatty cold water fish consumption (salmon) and soluble fiber (fruits, vegetables, oats) are sometimes used to treat lipids. Some individuals have tried combining statins and fibrates, but this combo can lead to an increase in muscle related disorders in some patients.
Conclusion
We have learned a lot during the past 10 years about body changes associated with HIV, but many more questions remain. It is the hope that those new to HAART therapy will not have to suffer the devastating drug side effects that their predecessors have had to contend with in the past 20 years. As patients, it is our responsibility to stay educated and learn from others about emerging options that may make it possible one day to live fully without HIV related body changes and other side effects.
For more information visit: http://www.facialwasting.org/ or to subscribe to the largest internet HIV health discussion group send a blank email to pozhealth-subscribe@yahoogroups.com
Nelson Vergel is director of Program for Wellness Restoration.
A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. AIDS. 1999 Sep 10;13(13):1659-67.
Metabolic Outcomes of ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI-, and NNRTI-sparing Regimens for Initial Treatment of HIV-1 Infection. Richard H. Haubrich, S Riddler, G DiRienzo et al.
More information is available at http://www.medibolics.com/.
More information is available at http://www.nucleomaxx.com/.
More information is available at http://www.facialwasting.org/.
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