The Use of Human Growth Hormone in the treatment of HIV / AIDS

HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). The HIV retrovirus may be passed from one person to another when infected blood, semen, vaginal secretions or other bodily fluids come in contact with an uninfected person's broken skin or mucous membranes. People with HIV have what is called HIV infection and are fit and well. Some of these people will develop AIDS as a result of their HIV infection.

Growth hormone is a popular bodybuilding and performance enhancing aid, and the use of recombinant human growth hormone (rHGH, or simply GH) to treat various conditions in HIV infection has been debated with excitement for years. Indeed it is licensed for the treatment of wasting syndrome in advanced stages of AIDS. GH is also a commonly used bodybuilding and performance enhancing drug, which can be purchased on the black market; used to help both muscle anabolism / strength and reduction in body fat levels. Both of these applications have possible significance in the treatment of HIV.

Other than in the treatment of wasting disease, results from the studies using rHGH to treat body changes associated with HIV and/or drugs used to treat HIV have been very favourable. One which has been studied extensively is the use of rHGH in reducing HIV-associated adipose redistribution syndrome (HARS). However, the positive effects of HGH treatment in HIV may be more direct. Several studies have proposed that rHGH may bolster the immune system in ways that might improve clinical outcomes in HIV.

Wasting
Like cancer cachexia, advanced stages of AIDS are characterised by severe muscle wasting and weakness. The reasons for this are because the patient often has a very poor appetite and food intake, as well as there being direct wasting effects from the HIV and some associated diseases which the patient may have, e.g. pneumonia. The patient then enters a downward cycle with diminished strength, poor food intake and further wasting, and it's often this which leads to eventual death.

Both anabolic steroids and rHGH therapy are used clinically to both slow the effects of wasting and to help improve appetite. Both have been shown to prolong life significantly and improve quality of life in advanced stages of AIDS.

HIV-associated adipose redistribution syndrome (HARS)
HARS is a type of lipodystrophy (abnormal distribution of body fat), where there is accumulation of excess truncal fat and visceral adipose tissue, as opposed to regular gynoid (glutes and hips) or android (abdomen) deposition. This is observed in HIV infected people, moreso as virus load increases. Although not a debilitating condition in itself (indeed extra body fat can prolong life if followed by wasting), HARS is unpleasant for the individual, giving reduced confidence in body image; another negative aspect of the disease. rHGH therapy has been shown to significantly reduce HARS, leading to an improved body image, and significant improvement in psychological well-being. Numerous studies have demonstrated the benefits of this, leading to rHGH being licesenced for the treatment of HARS in some countries. It should also be noted that improvement in psychological well-being could also contribute to a positive clinical outcome, in that it reduces the effects of wasting.

Immune system
Of most interest in HIV therapy are the possible benefits of rHGH use on the immune system, since HIV's primary adverse effect is reduction in the immune system. It has been clearly demonstrated that rHGH does benefit the immune system, but the method by which it helps is still under debate. One theory is that rHGH may stimulate renewal of the thymus gland, an important organ in the immune system. This may, in turn, lead to improved immune health in people with HIV. Studies are now examining whether or not renewing thymus tissue leads to better health and longer survival.

The thymus is necessary for developing new T-lymphocytes, which are key immune cells in the defence against disease, and numbers of which steadily reduce in HIV as infection progresses. In particular the thymus gland is involved in the development of CD4+ and CD8+ cells, and it is the CD4+ level which is a very critical marker in HIV outcome. Without some thymus activity, immune reconstitution that produces a wide range of functional CD4+ cells is not believed to be possible. Thus, the state of the thymus in HIV disease and how therapies affect it are of great interest to those researching ways to restore the immune system.

Napolitano et al  researched rHGH and its impact on the thymus in HIV. Doses ranged from 1.5 (4.5IU) to 3.0mg (9IU) per day for 6–12 months in healthy HIV volunteers. After six months, marked increases in thymus mass were noted, beyond what has been seen using anti-HIV therapy alone. This increase was sustained during the course of rHGH therapy and correlated with a higher CD4+ count, suggesting that the thymus is functioning properly and helping make new T-cells, further suggesting a stronger immune system. When rHGH was stopped, there was a loss of thymus mass; however, CD4+ cell count increases seen over the course of therapy were sustained despite this loss of mass.

Napolitano later did a twenty-person study using 3mg (9IU) rHGH a day injected under the skin (subcutaneous injection). This was followed by 1.5mg (4.5IU) rHGH a day for another six months, for a total of one year of daily therapy. Of the 20 volunteers (all of whom stayed on anti-HIV therapy during the study), ten took one year of rHGH according to the schedule described above while the other ten were merely observed. After one year, the group on rHGH stopped therapy and were observed for a second year, while the group who hadn't taken rHGH therapy then started one year of it. The size of the thymus increased in those on rHGH during the first year, but not among the second group. Those on rHGH had a significant increase in thymus mass while those only on anti-HIV therapy actually had a slight decrease.

Also, these increases in thymus size (together with increases in both thymus density and volume) related to marked increases in naïve CD4+ cells (69% increase among those taking rHGH during the first year compared to only 9% increase for those only on anti-HIV therapy), but not naïve CD8+ cells. This was further associated with more pronounced increases in total CD4+ cell counts (19% increase among those on rHGH versus 1% increase among those only on anti-HIV therapy).

Interestingly the most pronounced increase in both naïve and total CD4+ cell counts were seen among those on rHGH with a rise in the hormone IGF-1 (insulin-like growth factor-1) which is also associated with immune function. In subjects with pronounced increase in IGF-1 levels due to rHGH use, naïve cells increased by 95% and CD4+ increased by 25%.

The AIDS Clinical Trials Group (ACTG) conducted a larger 60-person study. One group was given anti-HIV therapy and 1.5mg (4.5IU) rHGH a day for 48 weeks. A second group took anti-HIV therapy alone for 24 weeks, followed by 3mg (9IU) rHGH a day for 24 weeks. By the end of 48 weeks, both groups showed notable increases in naïve and total CD4+ cell counts. The first group took rHGH for a longer period of time but were on a lower dose that took longer to result in CD4+ cell increases. However, people in the lower dose group showed more pronounced increase by week 48 in another measure of recent thymic activity called TREC (T cell receptor excision circles). Seven out of 11 people in the lower dose rHGH group showed increased thymus mass after 24 weeks while seven out of nine showed the same effect after 24 weeks on the higher dose.

Researchers at Imperial and Chelsea and Westminster Hospital in London (2006) administered rHGH therapy in chronic HIV patients in an attempt to reconstitute HIV specific CD4+ and CD8+ T-cell responses. While viral load and CD4+ and CD8+ counts remained unchanged, T-cell maturation and differentiation were significantly enhanced.

In all of these studies, using rHGH related to increases in thymus size and CD4+ T cell counts. Taken together these studies are promising, but they are not studies of effectiveness. Many questions remain unanswered about using rHGH to treat immune suppression in HIV disease. It does seem that there may be little benefit in respect of the immune system when CD4+ level is still at a reasonable level, but when it goes below an acceptable reference range then rHGH therapy may be worth considering. Obviously a high percentage of newly diagnosed patients are already in more advanced stages of the disease as they only present to their doctor when they have symptoms, so these may already have reduced CD4+.

Acute Infections
HIV patients are often more prone to acute infections which may take longer to clear up than in non-HIV individuals. Sometimes these can be associated with poor appetite and weight loss. rHGH therapy may curb rapid weight loss often associated with acute infections in HIV positive people and may also reduce length of infection. Far more research is needed here though.

Fasting lipid profile
HIV patients have been shown to have elevated serum lipids, and dyslipidaemia, i.e. high LDL (bad) cholesterol and low HDL (good) cholesterol with raised total cholesterol and triglycerides. This is associated with anti-HIV drug treatment especially later on in infection. This does increase risk of cardiovascular diseases, and rHGH treatment may improve lipid profiles.

Bone Building
HIV patients may have loss of bone density associated with wasting. Both treatment with rHGH and growth hormone releasing factor (GHRF) have indicated improved bone mass in HIV patients.

Side effects of rHGH treatment
Although we have focused on the promising benefits for rHGH treatment in HIV infection, consideration of possible side effects is important in ensuring an informed decision can be made. Side effects of rHGH therapy include possible joint pain (arthralgia), abnormal growth of the body's extremities and impaired glucose intolerance, increasing the risk of type 2 diabetes.

Caution is also advised against using over-the-counter or faddy internet products that claim to contain human growth hormone. Some of them claim to contain plant-derived growth hormone, others claim to contain cow or goat growth hormone, and still others claim to contain substances that increase the body's production of GH. There is no evidence that any of these products contain either a relevant product or a dose needed to induce the types of effects seen in studies. Over-the-counter and internet sales of these 'growth hormone' products are a major source of health fraud.

Certainly rHGH has shown benefits in treating wasting syndrome in advanced stages of HIV disease or AIDS, and its approval as a treatment for body lipodystrophy is encouraging. However, it's important that larger studies confirm these early findings. They can tell us whether or not increases in thymus size and CD4+ cell numbers, associated with rHGH use, ultimately benefit people living with HIV and result in better quality of life and longer life. Treatment with GH in HIV is encouraging and exciting, but far more research is still required.

Human growth hormone and HIV/AIDS

Human growth hormone (HGH) is a natural hormone produced in the pituitary gland, which promotes normal growth and development in the body. It activates protein production in muscle cells and the release of energy from fats. It is typically used to stimulate growth in children with hormone deficiency, or to treat people with severe illnesses, burns or infection where destruction of human tissue and muscle occurs.

A genetically engineered or ‘recombinant’ version of HGH has been produced (rHGH). Test tube experiments have shown that it can stimulate immune cells such as natural killer (NK) cells, which are related to tumour control and T-cells. rHGH is also known as somatrem or somatotropin. One form of HGH is made by Serono under the brand name Serostim, although other forms are made by other manufacturers. It is given as an injection under the skin.

rHGH is a licensed treatment that can be prescribed on the National Health Service for children with short stature as a result of growth hormone deficiency. However, it is not licensed for prescribing to people with HIV in Europe. rHGH is also very expensive to produce, casting doubt on the feasibility of its introduction into routine HIV care.

There has been some concern that the use of human growth hormone in people with HIV would stimulate viral replication and lead to increased viral load. However, recent evidence suggests that individuals who add growth hormone to their anti-HIV combination are likely to experience a small drop in viral load.

In HIV disease, HGH is best known as a treatment for HIV-related wasting, although it is not an approved treatment for this condition in Europe. High doses of HGH have been found to increase weight and lean body mass in people with AIDS wasting.  An increase in lean body mass is thought to be important in HIV disease because the loss of lean body mass is the form of wasting most closely related to an increased risk of death.

In August 1996, HGH was granted accelerated approval in the United States for the treatment of AIDS wasting. Studies of up to twelve weeks in duration have found that the drug may stabilise weight or reverse weight loss in people with HIV, although no improvements in survival were seen. The long-term safety and tolerability of HGH are unknown. In the European Union, HGH has been granted orphan drug status for the treatment of AIDS wasting, which means that Serono will have exclusive rights to market the product for this purpose in Europe, even though other companies also have their own versions of the treatment.

In a recent meta-analysis of treatments for wasting, rHGH was found to have similar efficacy to the other two major treatments, testosterone and anabolic steroids, with all three showing a significant benefit over placebo. However, rHGH may have advantages in terms of increasing muscle function and quality of life.

Clinical studies, including two randomised trials, have confirmed that HGH can reduce abdominal fat and increase muscle mass in people taking anti-HIV treatment. These improvements in body composition are paralleled by increases oxygen uptake, the ability to carry out moderate physical exercise, and the capacity for high-intensity exercise.

Reductions in ‘buffalo hump’ and breast size have also been reported, although breast development in men has been noted as a side-effect of rHGH. Improvements may reverse on stopping rHGH and may be more likely among individuals with mild body fat abnormalities.

The benefits of rHGH seem to be limited to boosting muscle and decreasing fat accumulation. It has no effect on fat loss in the face and limbs.

In addition to its possible beneficial effects on wasting and fat redistribution, recent studies have suggested that rHGH may improve CD4 cell counts in patients on antiretroviral therapy. In one randomised study addition of 1.5mg rHGH daily to antiretroviral therapy for 48 weeks increased CD4 cell counts by a median of 55 cells/mm3, while a shorter course of 3mg daily for 24 weeks improved CD4 cell counts by the same amount. Around half of this increase was in naive CD4 T-cells and it was coupled with an increase in the size and function of the thymus gland, the organ under the breastbone that produces new naive T-cells.

Further research is needed to establish whether these effects are paralleled by an improved ability to fight infection.

Side-effects of HGH can include headache, muscle pain, joint pain, salt and water retention and rare instances of carpal tunnel syndrome (pain or tingling in the first three or four fingers of the hand). Children treated with the drug over the long term develop antibodies to it, but these do not seem to have any harmful effects.

A large-scale study of rHGH in people with AIDS wasting identified several serious side-effects which were thought to be associated with rHGH. These included skin cancers, gastrointestinal bleeding, inflammation of the arteries, and breast development in men. Elevated triglycerides and the development of diabetes have also been reported among individuals taking rHGH with antiretroviral therapy-related body fat changes. In a randomised study of several HGH doses to treat AIDS wasting, glucose levels rose modestly in 28% of patients receiving a daily dose and 18% of patients receiving doses on alternate days. There was one case of new onset diabetes and two cases of hyperglycaemia amongst the 646 patients who received HGH for up to 24 weeks.

Anabolic steroids help AIDS patients

My hope is by sharing my story (which I’ve told to only a few friends) you also might be encouraged to document and share your own story about AIDS. It is our stories that are the heart and soul of the history of AIDS.  None should be forgotten. Ever.

It was in 1988 that a friend of mine introduced me to Dr. Walter Jekot, an HIV doctor practicing in Los Angeles. Dr. Jekot knew I was semi-retired at 24 and asked if I’d consult with him to help market his sports medicine practice in West Hollywood. The bulk of his patients were gay men, mostly bodybuilders and a few athletes. Why not, I thought. Partying every night was starting to get kind of boring anyway.

One Saturday afternoon, a couple of months into working with Dr. Jekot, two men wearing suits came into his office and closed the door. They stayed for more than three hours. After they left, I went in to ask Dr. Jekot what was going on. As I asked my first question, he just looked up and stared at me. He was ghost white. “What’s wrong,” I asked. “Sit down, Dave,” he replied. “There is something I have to tell you.”

He said the men were his attorneys. “I am being prosecuted by the federal government for what they say is the illegal distribution of anabolic steroids and growth hormone,” he explained. Then he told me his story.

After the 1988 Olympics in Los Angeles, scandal hit the sports world. Ben Johnson, a Canadian sprinter and gold medal winner that year, was to appear at a court hearing that would be broadcast live around the world. The government wanted to find out if Johnson could be prosecuted for cheating because he allegedly took anabolic steroids during the 1988 Olympic Games. During the trial, Johnson’s doctor said that Dr. Jekot had dispensed anabolic steroids to the U.S. Olympic athletes during the same Olympic Games.

Within 15 minutes every news agency in the world was beating down Dr. Jekot’s door, trying to get a comment, demanding an interview. A week later, the assistant attorney general of the United States announced on live television that the Department of Justice was going after Dr. Jekot with every legal resource available to the federal government.

I sat there stunned. I felt betrayed. I got up and started to leave, but he blocked the door. “Wait,” he asked.  “There is something else.”

First, he apologized for not telling me sooner. He said he was scared and didn’t know whom he could trust, including his own attorneys. “Did you do it,” I asked. When he said no, I sat down again.

He wanted to tell me something, he said, about a discovery he made, but I had to promise not to tell anyone else. I declined.  He told me anyway:  “I have discovered that anabolic steroids and growth hormones can help AIDS patients by reversing the wasting process.”

Wasting is the involuntary loss of body weight the entire gay community had seen time and again.

Having a sports management background, I had spent years warning our athletes about the ills of steroids. I was skeptical. In fact, I didn’t believe him. Why should I?  But some strange force kept me in that chair listening. I wanted to know more about the discovery that might help AIDS patients.

A month later I asked for and received written permission to have access to the medical records of 13 AIDS patients who were being treated with anabolic steroids or growth hormones for AIDS-related wasting. I also asked to be permitted to interview each patient. All agreed.

It was 1989. After sitting down with each of the 13 patients, I became convinced anabolic steroid treatments worked. I had no idea why or how, but something was keeping these patients alive. They had energy and looked healthy and fit.

Thus began my quest to have the most unpopular and denounced drug in the world become accepted as the therapy to reverse wasting syndrome and bring people back to life. I believe this was, in fact, the first Lazarus Effect treatment. Within three years, anabolic steroids became standard treatment to reverse AIDS-related wasting.

Anabolic Steroids Help People with HIV Gain Weight

People with HIV who are treated with anabolic steroids to prevent AIDS wasting may realize modest gains in weight and muscle mass, a new review shows.

The review covered 13 studies of adults age 24 to 42 with HIV, 294 of whom received anabolic steroids for at least six weeks and 238 of whom received placebo. The average weight increase in those taking anabolic steroids was nearly three pounds.

“The magnitude of weight gain observed may be considered clinically relevant,” said lead author Karen Johns, a medical assessment officer from the agency Health Canada. “One hopes there would be greater weight gain with the long-term use of anabolic steroids; however, this has not been proven to date in clinical trials.”

AIDS wasting, which leads to significant weight loss in people with HIV, causes severe loss of weight and muscle and can lead to muscle weakness, organ failure and shortened lifespan. Researchers have long sought to reverse this common, destructive effect of HIV with mixed success.

The wasting stems from loss of the body’s ability to grow muscle and from low levels of testosterone.

Anabolic steroids are synthetic substances similar to the male sex hormone testosterone that promote growth of skeletal muscle and the development of male sexual characteristics.

Although most recently in the news for their misuse by professional athletes, anabolic steroids have legitimate medical application for men with low testosterone and people with certain types of anemia. Two anabolic steroids available in the United States, nandrolone decanoate and oxandrolone, have been used to help increase weight and muscle mass in small studies of people with wasting.

Conversely, anabolic steroid use has been associated with increased rates of HIV in those who share needles or use nonsterile needles when they inject steroids.

In the review studies, anabolic steroids were administered to patients either orally or by injection. The main side effects were mild and included abnormal liver function tests; acne; mild increase in body hair; breast tenderness; increased libido, aggressiveness and irritability; and mood swings — all common side effect of anabolic steroid use.

“The risks and side effects of taking anabolic steroids long-term are certainly of concern,” Johns said. “We were unable to assess these risks in our review due to the short duration of treatment in the studies.”

Wayne Dodge, M.D., the HIV/AIDS program director at the Group Health Cooperative in Seattle, suggests that clinicians should obtain blood testosterone levels, “if an HIV-infected individual has had significant weight loss, significant fatigue or muscle wasting, and particularly if associated with a significant decrease in libido and erections. If [testosterone] is in the low or low-normal range then a trial of [steroids] could be tried. The individual and the clinician should decide what result would constitute a successful trial: weight gain of 15 pounds, a 30 percent improvement in sense of well-being [or] a successful erection once a week.”

The reviews authors conclude that further studies are needed to determine if increase in weight leads to improved physical functioning and quality of life, and ultimately increased survival, as well as the potential for serious side effects, especially with prolonged use.

Human Growth Hormone Being Used in AIDS patients

Serostim, a form of recombinant HGH  is being used to reverse the pernicious form of weight loss seen in later stage AIDS, called "wasting."

Wasting is different than the loss of weight and fat that comes from under eating, this wasting also occurs in later stages of cancer. Wasting is the unintentional loss of weight in which the lean muscle, the body mass, the bones and the body organs are all withering away. Many experts believe this loss of lean body mass contributes to immune dysfunction and makes it harder for AIDS patients to fight off life-threatening infections. The wasting process itself, if it goes beyond about 33% of ideal body weight, is incompatible with life, as was seen in concentration camp victims of World War II.

A number of medical centers took part in a study of 178 patients with AIDS-associated wasting, which is defined as having lost at least 10% of body weight. The patients who received growth hormone therapy gained an average of 6.6 pounds of lean body mass while losing an average of three pounds of fat after three months of treatment. The therapy also resulted in an improvement of their endurance and quality of life.

Dr. Schambelan, of UCSF says "At the moment there isn't another therapy in the late stages of AIDS that has had this kind of effect on the lean body mass." "There are therapies that can increase weight, such as an appetite stimulant called megestroacetate, but that weight gain tends to be primarily fat. The advantage of growth hormone is that it causes lean body mass to increase." Dr. Schambelan says that some of the patients are still coming in, even though the original study ended three years ago. "Obviously these are the people who are still alive and doing well and the people who didn't do well are no longer there, so you can't talk about the average effect. I think that the anecdotal experience is that for the people who continue to take the drug, who continue to eat, and don't get serious opportunistic infections, they have had a very robust response. The medication has increased the benefits. The gain in lean body mass they had in their three months of the study has doubled or tripled over the next year or two."

 Although human growth hormone does not cure AIDS, there is some evidence that it may lengthen the life of AIDS patients. The increase in lean body mass may make the AIDS patient less vulnerable to infections. When given with antiviral agents such as AZT, human growth hormone did not cause any increase in the amount of HIV. In fact, human growth hormone has been shown to stimulate the formation of new red blood cells, which are depleted by AZT.

Even more exciting, human growth hormone also appears to reduce the incidence of AIDS associated infections, such as polycystic pneumonia and Kaposi's sarcoma. It can rejuvenate the immune system; if it can actually strengthen the ability of HIV+ patients to resist infectious diseases it may improve both the quality and the quantity of their lives.