Monthly Archives - November 2007

HIV Metabolic Complications Myths

HIV Metabolic Complications MythsSome misunderstandings about treatment
by David Alain Wohl, M.D.

Introduction
One of the greatest drags on the success of potent antiretroviral (ARV) therapy has been the fear of metabolic complications associated with these medications. Disfiguring body shape changes including the loss of fat in the face, as well as unhealthy cholesterol and triglyceride levels and pre-diabetes are troublesome counter-balances to the euphoria that arose when these drugs arrived and people stopped dying. Even as ARVs have become more user-friendly—less pills, less frequent dosing, less diarrhea and nausea—the specter of metabolic problems can still overshadow these advances, leading those in need of therapy to hesitate when ARVs are recommended. For those already on treatment, metabolic disorders may prompt a change in therapy or lead to the prescription of even more medication and can raise the volume of the little voice that says it is okay to skip doses.
A major frustration for people living with HIV and their health care providers has been a lack of information regarding the cause of metabolic problems during HIV infection and ways to prevent and treat them. The field of metabolic complications of HIV and its therapies is relatively young and much has been learned during a short period of time but some conclusions have been reached with little supportive data. Below is a list of some of the most common of these metabolic complications myths. Myths that emerged in a data vacuum and that even people in the “HIV-know” often still accept. Fortunately, over the past few years a slew of studies has painted a clearer picture of these changes and together suggest that some of our closely-held beliefs about the risks for metabolic complications have been wrong. Understanding that these assumptions are no longer valid, and why, is essential if people living with this infection and their health care providers are to make informed decisions about their care.

Myth #1: Protease inhibitors are responsible for the increases in belly fat.
Like many myths, this one is based on a truth that has been stretched to extremes. People taking protease inhibitors can see an increase in their belly fat, both the deep down fat that surrounds our internal organs and the surface, pinch-an-inch fat so abundant in our land of amber waves of grain. But protease inhibitors hold no monopoly on an ability to expand trunk fat. Studies of efavirenz (Sustiva) have shown that people taking this non-nucleoside also tend to have increases in belly fat. In fact, increases in waist size have been seen in studies of every HIV regimen in which body shape has been objectively measured. For example, in a federally funded AIDS Clinical Trials Group (ACTG) clinical trial called study A5142 comparing the popular HIV medications lopinavir/ritonavir (Kaletra) and efavirenz, trunk fat was seen to increase in participants regardless of which drug they were assigned. Similarly, a Bristol-Myers Squibb sponsored head-to-head study of efavirenz and another protease inhibitor, atazanavir (Reyataz), in patients who were starting HIV therapy also found that both drugs when combined with zidovudine and lamivudine (Retrovir and Epivir, also Combivir) tended to increase abdominal fat over time. Interestingly, a recent Abbott Laboratories study that looked at using lopinavir/ritonavir by itself (i.e. monotherapy) in patients started on this protease inhibitor and zidovudine/lamivudine found that these patients experienced increases in belly fat to the same extent as a control group of patients who were maintained on zidovudine/lamivuine and efavirenz. Therefore, it looks like both protease inhibitors and, at least, the non-nucleoside efavirenz can lead to gains in belly fat.
A problem for most all of these studies is that they rely on a special type of scan called a DEXA to measure abdominal fat. This scan, commonly used to also measure bone density, cannot tell the difference between the deep and surface fat. So, one therapy could be causing accumulation of the deeper fat while another could be associated with surface fat. CT and MRI scans, however, can differentiate deep and surface fat. Unfortunately, we do not have much data regarding the relative changes in fat in deep and surface fat for most HIV regimens. Clearly, more studies need to be done on other regimens, including those that contain newer drugs, and should use CT scans when possible but one thing is clear: when it comes to increasing belly fat, protease inhibitors are not unique.

Myth #2: People who get bigger bellies on HIV meds typically also lose fat in their arms and legs.
As if a big spare tire was not bad enough, some people taking HIV medications also experience loss of fat of the arms, legs, and face. The image of an apple-shaped body with skinny limbs is a frightening one that further turns many people off to HIV therapy. However, it has become clear that most people on HIV medications do not develop this body shape. In fact, a couple of studies of people starting a variety of HIV regimens have found that for most people limb and belly fat tend to increase or decrease together. That is, if someone experiences a gain in belly fat then they are more likely to also experience a gain rather than a loss in limb fat. In one study, only a quarter of people experienced a loss of arm and leg fat while gaining abdominal fat.
Most studies suggest that overall fat gain is a major problem for HIV-positive people. As in the general population, being overweight and obese is common. In a study of HIV-infected patients receiving care in Philadelphia, rates of being overweight and obesity were more of a problem than weight loss. As people with HIV infection look to decades of living with their infection, the problem of obesity is likely to take its toll since obesity increases the risk of diabetes, heart disease and death.

Myth #3: Loss of limb fat during HIV therapy only occurs when stavudine (d4T) is included in the treatment regimen.
The profound loss of fat within the arms, legs and especially the face among people on HIV medication cocktails that was seen in the mid-1990s was quickly associated with one drug, stavudine (Zerit). The link between such disfigurement and this drug was so obvious that use of stavudine in the U.S. and Europe quickly fell and is now rarely prescribed (unfortunately, stavudine is still commonly used in developing nations as it is easy to make and, thus, cheap).
The drop in stavudine use was followed by a dramatic reduction in new cases of severe fat loss of the face and limbs. However, over time some doctors and their patients noticed a slower but undeniable depletion of fat in these same areas of the body. But, as these changes were slow to develop and DEXA, CT, and MRI scans are not routinely performed in clinics to measure and follow body fat changes, it was unclear whether these changes were real and, if so, what caused them. What was clear was that these people seemed to be losing limb and face fat but had never taken stavudine.
Some answers came from clinical trials that incorporated DEXA scans into their design. One study done several years ago by the ACTG found that people starting HIV therapy who took the protease inhibitor nelfinavir (Viracept) were more likely to lose limb fat—as measured by DEXA scans—than those taking efavirenz, even when the other medication taken was limited to zidovudine/lamivudine (Combivir). This meant that people on zidovudine/lamivudine were experiencing fat loss and that this was accelerated with nelfinavir use. Another study comparing zidovudine/lamivudine with tenofovir/emtricitabine (Truvada) when both were taken with efavirenz found that there was a progressive loss of fat among those assigned to zidovudine/lamivudine while those taking tenofovir/emtricitabine gained limb fat over time.

The ACTG study A5142 looking at people new to HIV medications also performed DEXA scans before HIV medications were initiated and then at regular intervals after starting the drugs. This was a large study of almost 750 people who were assigned to one of three different study treatments: a.) lopinavir/ritonavir plus two nucleosides, or b.) efavirenz plus two nucleosides, or c.) lopinavir/ritonavir plus efavirenz alone without nucleosides. Those taking nucleosides could use only lamivudine plus either stavudine, zidovudine or tenofovir (Viread). The study is very important as efavirenz and lopinavir/ritonavir are two of the most popular medications used to treat HIV infection yet, had never been compared before. The results of this trial have shaken the field of body shape changes during HIV treatment. Those taking stavudine had, as expected, the greatest loss of limb fat and those taking tenofovir had the least. But, zidovudine fell in between. This alone indicated that some people experienced limb fat loss even when not receiving stavudine and that zidovudine was capable of doing this to a greater extent than many had thought. In addition, the study found that no matter what nucleoside was used, efavirenz was more likely to cause significant fat loss compared to lopinavir/ritonavir. That is, efavirenz seemed to add to the fat loss that was associated with the nucleosides. The good news is that few of those on tenofovir lost significant amounts of limb fat at 96 weeks of study, even when on efavirenz, so fear of fat loss should not be a major concern for those who are taking or considering use of tenofovir plus efavirenz (two of the three medications in Atripla).
Taken together, these data indicate that fat loss of the arms and legs is not limited to stavudine and that other drugs can also produce these changes. Zidovudine appears to be worse than tenofovir (or abacavir [Ziagen]), albeit it is not as bad as stavudine. Additionally, efavirenz seems to be able to dial-up the fat loss effect of nucleosides to a greater extent than lopinavir/ritonavir. Unfortunately, there is not much information regarding face fat from any of these studies.

Myth #4: Sit-ups can spot reduce belly fat.This myth falls into the same category as the belief that going out with wet hair will increase your risk for a death of a cold and that too much time spent self-pleasuring can wreak havoc on your visual acuity. A remarkable number of intelligent men and women arrive at their clinic visits complaining of increases in belly fat, and are frustrated that endless sit-ups have done nothing to reduce their mid-body girth.
Sit-ups, when done properly, can increase strength in the abdominal muscles. This leads to firmer muscles and an increase in core strength but will not melt away fat in that one area. Fat is lost when more energy is expended than taken in. While sit-ups require energy, they do not preferentially draw that energy from the deposit of fat cells found in those love handles. A better approach is to combine sit-ups with aerobic exercises that require heavy breathing and sweating for prolonged periods of time like running, cycling, stair climbing, rope jumping, etc. Small studies have shown decreases in abdominal fat when HIV-positive people followed a program of aerobic exercise and weight lifting several times a week.
Diet can also play a role here and a smart approach would be to limit simple sugars and the highly caloric fats that make up most of the so-called comfort foods of our society. For most people dietary modification need not be very complicated and can be summed up with a recommendation to greatly increase daily intake of fruits and vegetables, the latter preferably raw or lightly steamed. These are foods that are not packed with excess calories, contain cholesterol-lowering fiber and are filling—leaving less room for the fatty, super-size-me foods at the root of many of our health problems.
In addition to eating like a Buddhist monk and joining a gym there are other interventions that have been studied to reduce excess fat. Unfortunately, few have panned out. Growth hormone is an injectable agent that has been found to reduce fat in the belly and buffalo hump and some people have benefited from this therapy. However, this is an expensive drug that is not usually covered by insurance carriers for the treatment of excess fat. Also, at the doses studied for the treatment of excess fat, growth hormone has been plagued by a number of troublesome side effects including worsening glucose levels, muscle and joint aches, and feet swelling. Interestingly, exercise is known to increase the body’s own production of growth hormone.
Testosterone and other androgens (“male hormones”) have also been studied as treatments for fat accumulation in people with HIV infection. These hormones, like growth hormone, can pop fat cells but in another ACTG study were found to preferentially reduce the surface fat and not the deep fat that made for most of the enlargement of the belly. Androgens can also worsen limb and face fat loss. Therefore, although beloved by many, the data suggest that androgens may do little to reduce abdominal girth and can aggravate loss of fat beyond the trunk.
A few drugs used for the treatment of diabetes have also been studied for fat accumulation, including metformin, rosiglitazone, and pioglitazone. Most of the data informing the use of these drugs in people with HIV come from small studies. Suffice to say that their effects, if present at all, seem to be mostly limited to those with diabetes or a pre-diabetes condition. The underwhelming study results and the toxicities of these medications have diminished any enthusiasm for dedicated use of these drugs to treat fat changes in people with HIV infection.

Myth #5: People with HIV infection have higher cholesterol levels than people without HIV.
Take a survey of people living with HIV or even their docs and ask whether HIVers have higher cholesterol levels than those without HIV. Chances are most would respond that those who are HIV-positive would, on average, have higher levels than those who are uninfected. Actually, at least a couple of studies have found that people with HIV infection tend to have lower levels of LDL cholesterol, the “bad” cholesterol that has been strongly linked to heart disease, than people in general; this finding holds even when including those who are on HIV medications.
This does not mean that those with HIV infection have a better lipid profile than uninfected folks. A major problem is that levels of the “good” cholesterol, HDL cholesterol, are also lower in HIV-positive people. HDL cholesterol has been found to offer protection from heart disease and a low level is an independent risk factor for cardiovascular problems. Exercise and modest alcohol (not just red wine) intake can safely raise HDL cholesterol in some people. In addition, a little appreciated fact is that certain HIV medications also raise HDL cholesterol levels. The non-nucleosides efavirenz and nevirapine [Viramune] and the protease inhibitor atazanavir alone or in combination with ritonavir [Norvir] and most all other protease inhibitors that are boosted with ritonavir have all been found to raise HDL cholesterol levels.

Triglyceride levels, though, are a different story. Triglycerides are broken down in the body from fat and can be found floating free in the blood or in a complex with other lipids and proteins in the form of cholesterol. The more triglycerides in the cholesterol complex, the more dangerous it is in terms of cardiovascular risk with LDL cholesterol having more triglycerides than HDL cholesterol. Fasting triglyceride levels are, on average, higher in people with HIV infection and increases further with HIV therapy. While in some people the level of triglycerides can skyrocket to very concerning levels (greater than 500 mg/dL) most people with HIV infection have levels that are high but not alarming. In addition, by itself the level of triglycerides measured in the blood is not considered as nearly big a risk for cardiovascular disease as high LDL or low HDL cholesterol. Most all HIV regimens can raise triglyceride levels. The ritonavir-boosted protease inhibitors are a bit worse in this regard than efavirenz, and most studies suggest that lopinavir/ritonavir and fos-amprenavir/ritonavir (Lexiva/Norvir) may raise triglyceride levels a bit more than other commonly-used boosted protease inhibitors, but the clinical significance of these modest differences is not clear.
Overall, the data suggest that people with HIV may be at greater risk of cardiovascular problems like heart attacks due to their low HDL cholesterol levels and possibly increases in LDL cholesterol and triglyceride levels during HIV therapy. Additionally, there may be other factors such as inflammation caused by the virus that can lead to chemical changes in the body that can prompt clogging of the arteries. However, it is almost certain that smoking adds much more to the risk of cardiovascular disease than these other HIV-related factors and that of all the things a person with HIV infection could do to survive and thrive, beyond taking HIV medications when necessary, the most significant is to stop smoking.

Summary

Clinicians and their patients do not tolerate ambiguity well. Gaps in knowledge of a disease demand to be filled and when the research data come up short it is difficult not to extrapolate. In the 25 years since the AIDS pandemic ignited, much has been learned about HIV and the crowning achievement of the scientists, clinicians, and advocates dedicated to this disease has been the dramatic reversal of the lethality of this disease. However, in HIV, as in medicine in general, it has been difficult to not jump to conclusions when data are conflicting or just plain not in existence.
In the case of metabolic complications of HIV and its treatments, we have learned to learn. New investigations have revealed the accuracy and inaccuracy of previous assumptions and allow us opportunities to better choose among our options. The trick is we have to be willing to let go of our old beliefs and embrace findings that rigorously challenge these concepts. The old mantra that knowledge=power still holds, but we have to accept that better knowledge=even more power.

Dr. Wohl is an Associate Professor of Infectious Diseases and Co-Director of the AIDS Clinical Trials Unit at the University of North Carolina. Metabolic complications associated with HIV infection and the nexus between HIV and incarceration are his major areas of research interest. He can be reached via e-mail at wohl@med.unc.edu.

We need action by Dec 6!:A Bush double-cross on HIV travel ban

Background:

A Bush double-cross on HIV travel ban
Tuesday, November 20, 2007

The Bush administration is trying to pull a fast one rushing through draconian proposed new regulations that will restrict even further the entry of HIV-positive people into to the US, just one year after having promised to ease them.

By Doug Ireland

The Bush administration is trying to pull a fast one rushing through draconian proposed new regulations that will restrict even further the entry of HIV-positive people into to the US, just one year after having promised to ease them.

On November 6, the Department of Homeland Security (DHS) issued stringent proposed new regulations for HIV-positive travelers coming here which are pretty regressive and extremely troubling, according to Nancy Ordover, assistant director for federal affairs and research at the Gay Mens Health Crisis (GMHC).

But the 30-day deadline for public comment imposed by DHS means a cut-off date of December 6 for reactions to the new regs, leaving little time for the AIDS advocacy community to mobilize.

That, Ordover told Gay City News, is a departure from standard practice for proposed new federal regulations; the time frame for public reaction is usually much longer, she said.

The US is one of only 13 countries that completely ban incoming travel across their borders by the HIV-positive. The others, according to a list established by the leading German AIDS service organization, Deutsche AIDS Hillfe, for the most part have undemocratic regimes. They are Iraq, China, Saudi Arabia, Libya, Sudan, Qatar, Brunei, Oman, Moldova, Russia, Armenia, and South Korea.

A waiver to the ban is required for HIV-positive travelers to or through the US. Even when a travelers US stay merely involves changing planes, a waiver is needed.

Last year on World AIDS Day, President George W. Bush pledged to issue streamlined new regulations with a categorical waiver that would make it easier for the HIV-positive to receive exemptions.

Unfortunately, despite using the terms streamlined and categorical, in reality these regulations are neither, said Victoria Neilson, legal director of Immigration Equality, which works on behalf of LGBT and HIV-positive asylum seekers and immigrants.

Neilson told Gay City News, This is a big disappointment, given the rhetoric of the Bush administration that the US was making it easier because the new regs simply add more heavy burdens for the HIV-positive traveler.

Among other provisions, under the new rules proposed by DHS, a visitor would need to travel with all the medication he would need during his stay in the US; prove that he has medical insurance that is accepted in the US and would cover any medical contingency; and prove that he wont engage in behavior that might put the American public at risk. The maximum term for any waiver would be 30 days.

The new regulations purport to speed up the waiver application process because consular officers would be empowered to make decisions without seeking DHS sign-off. However, by using this streamlined application process, waiver applicants would have to agree to give up the ability to apply for any change in status while in the US, including applying for legal permanent residence.

The purpose of fast-tracking the new regs and setting a super-tight December 6 deadline for public comment before they take effect was to catch the AIDS community busy with preparations for World AIDS Day on December 1 unawares. To a certain extent, the ploy has worked.

When Gay City News telephoned the usually well-informed Kate Krauss who has worked for several AIDS advocacy organizations and now coordinates the Health Action AIDS Campaign for Physicians for Human Rights to find out what she thought of the proposed new regs, she hadnt yet heard of them.

Wow, they just flew right by me they havent been on my radar screen at all, she said.

After having been provided by Gay City News with a copy of the proposal, Krauss was appalled.

Under the proposed regulations, the US travel ban remains a cruel violation of human rights for people with AIDS, Krauss said, adding, People with HIV would be made to jump through even more hoops than before, and the rules would make it particularly difficult for people from very poor nations to visit the US, with requirements for wealth, medical care, medications, and documentation that the applicant is HIV-positive.

Moreover, Krauss said, People could be penalized if they became sick while visiting the United States and, if found to be out of compliance with these regulations, barred from ever visiting the US again. If President Bush cares about the human rights of people with AIDS, he should just ask Congress to abolish the travel ban. Anything else is just rewriting an unjust policy.

GMHCs Ordover pointed out, As written, the rule could leave individuals with HIV who obtain asylum in the US in a permanent limbo; forever barred from obtaining legal permanent residence, and therefore cut off from services, benefits, and employment opportunities.

Ordover added, It seems very disingenuous that the government is claiming to make things easier for people with HIV, but its really compelling them to forfeit their rights.

As a result of the hasty release of the proposed regs and the arbitrarily truncated time frame for public comment, only a few AIDS advocacy organizations have so far taken a critical posture, and this only began to happen at the end of last week.

GMHC was the first organization to release a lengthy analysis of the new regs, which it did last Friday, and began preparing a sign-on statement protesting them which it will ask other AIDS advocacy groups and immigrant rights organizations to join.

But things were fairly sluggish at AIDS Action Council, the largest Washington, DC AIDS lobby, which bills itself as the national voice on AIDS and represents more than 3,000 local service organizations. When Gay City News this Monday asked Ronald Johnson, AIDS Actions deputy executive director, for his organizations position on the new regs, he would only say, we are in the process of developing our comments and we are still looking at the fine print.

Johnson added, Well probably follow GMHCs analysis.

When this reporter suggested to Johnson that AIDS Action organize a national conference call with executive directors of AIDS advocacy organizations to mobilize them quickly against the harsh new regs, he said theyd think about it.

Fortunately, GMHC is already in the process of organizing such a conference call for next week, Ordover told Gay City News.

However, said Ordover, these regulations are in general a distraction what we really need to move forward on is getting the HIV-positive travel bar overturned completely.

In addition to her other duties at GHMC, Ordover is co-coordinator of Lift the Bar, a coalition of HIV, immigrant, human rights, and LGBT service and advocacy organizations working to overturn the HIV ban.

At a Congressional hearing last November, Ordover detailed the negative consequences of the travel ban.

The HIV bar rarely makes the news, and when we do hear about it, its usually because someone trying to attend some major event or forum being held in the US cant get into the country, Ordover said. This is not unimportant the International AIDS Conference hasnt been held on US soil for 16 years and the HIV bar is the reason. Despite our efforts in the global fight against HIV and AIDS, our standing in the international community has been grievously compromised by this policy.

Ordover, who noted that one-third of GMHCs clients are immigrants, also pointed out, Many people first learn they are HIV-positive after they get to the US. Many contract HIV here. Some find out their status when they get the results of their Immigration Service medical examination.

Under the current DHS regs in force, she said, Visitors either are actively deterred from seeking HIV testing and treatment, or avoid contact with providers out of fear of putting their immigration status in permanent limbo or worse. If they are low-income or poor, they either dont have recourse to the full slate of public programs and services they need to stay healthy or may be unaware of what services they are entitled to. At GMHC we view this policy as a violation of human rights and a threat to public health inside and outside the US. The proposed new regs do nothing to change this.

And, Ordover added, The truth is, the bar undermines public health and drives up the cost of health care. It forces HIV-positive immigrants to go underground, discourages immigrants who dont know their status from getting tested, from seeking preventive care, from seeking any care until they end up in the emergency room with full blown AIDS all things that undermine individual health, public health and that ultimately put more strain on the public coffers.

Individuals who wish to protest the harsh new DHS regs on HIV-positive travel may submit comments online at click – but to do so you must include the docket number of the proposed regs, USCBP-2007-0084. Organizations wishing to join in signing on to the statement GMHC is preparing in protest of the new regs should contact Nancy Ordover at nancyo@gmhc.org or 212-367-1240. Doug Ireland can be reached through his blog, DIRELAND, at click.

SOURCE: Gay City News
http://www.gaycitynews.com/site/news.cfm?newsid=19044628&BRD…

This is the proposed rule
http://federalregistersearch.com/2007/11/6/E7-21841.asp

Submitted comments should be mailed to:
Border Security Regulations Branch, Customs and Border Protection, 1300 Pennsylvania Avenue, NW. (Mint Annex), Washington, DC 20229.

Include this in your letter:

Reference:
[Federal Register: November 6, 2007 (Volume 72, Number 214)]
[Proposed Rules]
[Page 62593-62600]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr06no07-15]

DEPARTMENT OF HOMELAND SECURITY

Bureau of Customs and Border Protection

8 CFR Parts 100 and 212

[USCBP-2007-0084]
RIN 1651-AA71

“Issuance of a Visa and Authorization for Temporary Admission Into
the United States for Certain Nonimmigrant Aliens Infected With HIV”

Human Experimentation in Anabolic Steroid Research

worked with Dr Scally in the past and he is one of the country’s experts on anabolic research. This is an e-book he just published.

America’s Nuremberg – Human Experimentation in Anabolic Steroid Research by Michael Scally MD (eBook)

“America’s Nuremberg – Human Experimentation in Anabolic Steroid Research” is a discussion of the ethical, medical, and legal violations for human subject protections in anabolic steroid research. Michael Scally, M.D. painstakingly chronicles current day human research abuses. The book describes how the ongoing public health and welfare is in danger due to government ignorance, pharmaceutical industry funding, and medical research community complicity. The money involved easily exceeds hundreds of millions of dollars. Those individuals affected number into the hundreds of thousands.

More Info:
http://www.mesomorphosis.com/store/anabolic-steroid-research-ebook.html