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.

The Effects of Oxandralone on Body Weight and Composition in Patients with HIV-Associated Weight Loss

A variety of anabolic steroids are in use to help counteract the severe loss of body weight that effects many patients with advanced HIV disease. Studies have previously shown that HIV-related wasting causes the destruction of body cell mass (or BCM: active muscle and tissue) while leaving fat stores relatively untouched, so treatments that preserve or help regain healthy, active body tissue are obviously important.

This open-label observational study enrolled 572 patients (527 men and 45 women) with a mean age of 40 years and a mean baseline weight of 68.1 kilograms. Patients were on stable antiretroviral regimens, had documented weight loss, and had no active opportunistic infections or cancers. All patients were treated daily with 20 mg of oxandrolone, an anabolic steroid in pill form. Study visits were scheduled after 1, 2, 4, 8 and 12 months. At each visit, patients were weighed, asked to assess their appetite, sense of well-being, and energy levels, and underwent bioelectric impedance assay (BIA) analysis. BIA measures body cell mass, amount of water in the body, and fat vs. muscle ratio.

Only 26 of the 572 patients had completed the full year-long study before Geneva, but their results, and the interim results from other the patients, were promising. Among the first 26, mean increases in total body weight (and body cell mass, listed in parentheses) were as follows:

• Month 1 2.4 kg total (1.4 kg of which was BCM)
• Month 2 2.8 kg (1.5 kg)
• Month 4 4.4 kg (2.1 kg)
• Month 8 5.4 kg (3.1 kg)
• Month 12 6.1 kg (3.5 kg) 

Patients' self-assessment also improved, with increased appetite and sense of well-being, and oxandralone was generally well-tolerated, with fewer than one percent of patients experiencing liver function test abnormalities, a side effect associated with anabolic steroids. Most side effects were managed with dose reductions. 

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.

For some, steroid use builds hope

A few years after his HIV diagnosis, Nelson Vergel began wasting away. No matter how much he ate, no matter how many protein shakes he added to his diet, no matter how much iron he pumped, the chemical engineer could not regain 25 pounds the virus had stripped from his 5-foot-7 frame. He watched as dozens of HIV-infected friends progressively lost body fat and muscle, and, ultimately, their lives. "Either I have to do something," Vergel thought, "or I'll be the next one." Then he found anabolic steroids.

For more than a decade, Vergel has been among the chronically ill patients who take anabolic steroids - legally - for the same fundamental reason some athletes use them on the sly: to build up their bodies. A storm of attention has been paid of late to illicit use of steroids among athletes, who forever want to run faster and hit balls farther. But at the same time, a quiet movement is under way to discover what legitimate role the drugs can play in mainstream medicine.

For years, doctors have prescribed anabolic steroids for those with HIV or AIDS, kidney disease, cancer and other illnesses that cause malnutrition or muscle wasting that can leave patients dangerously thin. And, although the long-term side effects of anabolics aren't fully known, even at low doses, some physicians see definite therapeutic benefits.

"Not only do they help rebuild muscle, they make you feel better," said Dr. Bruce Rashbaum, a Washington internist who has prescribed anabolic steroids to HIV and AIDS patients for 15 years. "It's not as if these patients are going to become Hercules, because they aren't going to be."

Not all doctors think the benefits of prescribing anabolic steroids for chronic conditions outweigh the potential risks, however. What's more, they say, simply adding muscle to a frail body isn't necessarily going to help someone who is dying from a disease anyway. But given the difficulty physicians have had in helping severely malnourished people gain lean muscle tissue -- as opposed to fat - scientists are continuing to study whether steroids might be among the answers.

Said Rashbaum: "Everyone has this notion that these drugs are taboo, and they don't even entertain the idea of learning about it. I really think in the short and long run the benefit certainly outweighs the risk for those patients that really need them."

In 1999, Dr. Kirsten L. Johansen, director of dialysis at the San Francisco VA Medical Center, led a study of 29 patients with kidney failure. Over six months, they were either injected with an anabolic steroid or given a dummy pill. Those in the drug group gained an average of nearly six pounds more in lean body mass - and reported less fatigue - than those taking the placebo. Johansen has been following up on that research to determine whether the patients' boost in weight was attributable to muscle and whether it translated into better physical function and quality of life.

"We know that people who lose muscle mass tend to die sooner," she said. "But what we really don't know is: If we build muscle mass, are we helping them? These patients are really debilitated. For some of them, that's just such an issue that they really might benefit from this."

Anabolic steroids date to the 1930s, when scientists created a synthetic form of the male hormone Testosterone. They were targeting hypogonadism, a condition in which the testes don't produce enough testosterone for normal growth and sexual function. Soon, researchers discovered that the drug aided the growth of skeletal muscle, too.

But not without a price: Anabolic steroids have been linked to side effects ranging from acne and aggression to cardiovascular disease and liver cancer. This type of steroid, which differs chemically from the corticosteroids commonly used to treat inflammation - is available legally in the United States only by prescription. And athletes typically take doses considerably higher than those prescribed for medical purposes.

Dr. Marc K. Hellerstein, professor of medicine at the University of California, San Francisco, said modest doses of anabolics, combined with weight training -- if patients are well enough to exercise - yield the best result.

He has used that approach for patients with HIV and AIDS. In a 1999 study he led, 22 men lifted weights and received testosterone by injection. Half also took an oral anabolic steroid.
Both groups increased their lean body mass, weight and strength. But those in the steroid group had significantly larger gains. "It was not just cosmetic; this was useful muscle," Hellerstein said. Even at low doses, anabolic steroids can have unpleasant or dangerous side effects, including liver damage and prostate cancer, and doctors who prescribe them have to monitor their patients closely.

In Hellerstein's study, those side effects included a drop in HDL (the "good" cholesterol), as well as irritability and overly aggressive behavior. In general, some patients don't like steroids because the drugs can cause sleep problems or make them more likely to pick fights with their partners. But others thrive on them.

Dr. Adrian S. Dobs, an endocrinologist at the Johns Hopkins School of Medicine, said she believes there's a limited role for anabolics in medicine, including with HIV and AIDS patients. But in other cases, she says, the long-term risks - which are still unknown - might be too great. "I just don't think there's good data to say it's really worth doing, with the exception of a few disease states," she said. "Increasing muscle mass per se is not a benefit. ... Are you doing any good? What's going on with the underlying disease?"

Vergel, who has been taking anabolic steroids since 1994, credits them with helping him through a difficult period before the advent of effective antiviral treatments that helped reduce chronic wasting. During his first four months injecting anabolics, Vergel put on 35 pounds, enough to push him up to 175, more than he weighed when he was healthy. The 46-year-old, who lives in Houston, kept up with the drug regimen and saw his white blood cell count climb. His energy and appetite improved. "I was looking great," he said. "For the first time, I was looking like I was not HIV-positive. I just felt like a superman. I just thought, 'Maybe I'll survive.'"

Vergel, who still takes a regular course of anti-HIV drugs, weighs 190 pounds and looks like a bodybuilder, founded a nonprofit group called PoWeR - Program for Wellness Restoration.

He eventually left his job and wrote a book outlining a health plan for HIV-positive people based on steroids, exercise and nutrition. Anabolics, he says, are only a part of the equation.
A doctor supervises his use of the drugs, regularly checking for changes in liver function and blood pressure and screening for prostate cancer. "When you're sick, the risk-to-benefit ratio changes in your mind,"

Vergel said. "I have no doubt that my quality of life and my life have been extended."