Human growth hormone to the treatment of the wasting syndrome of HIV/AIDS

Human growth hormone (HGH) is a naturally occurring polypeptide hormone secreted by the pituitary gland and is essential for body growth. Daily secretion of HGH increases throughout childhood, peaking during adolescence, and steadily declining thereafter. In 1985, synthetic HGH was developed and approved by the FDA for specific uses. However, it is commonly abused by athletes, bodybuilders, and aging adults for its ability increase muscle mass and decrease body fat, as well as its purported potential to improve athletic performance and reverse the effects of aging.

Several FDA-approved injectable HGH preparations are available by prescription from a supervising physician for clearly and narrowly defined indications. In children, HGH is approved for the treatment of poor growth due to Turner’s syndrome, Prader-Willi syndrome and chronic renal insufficiency, HGH insufficiency/deficiency, for children born small for gestational age, and for idiopathic short stature. Accepted medical uses in adults include but are not limited to the treatment of the wasting syndrome of HIV/AIDS and HGH deficiency. Dependent on the clinical presentation, pediatric dosages range from 24-100 microgram/kilogram/day and adult dosages from 0.9-25 microgram/kilogram/day, dependent on product. The FDA-approved injectable formulations are available as liquid preparations, or as powder with a diluent for reconstitution.

Using recombinant DNA technology, two forms of synthetic HGH were developed, Somatropin and Somatrem. Somatropin is identical to the endogenous pituitary-derived HGH, whereas Somatrem has an extra amino acid on the N-terminus. Both synthetic forms have similar biological actions and potencies as the endogenous HGH polypeptide. Synthetic HGH also is chemically indistinguishable from the naturally occurring hormone in blood and urine tests.

HGH binds to growth hormone receptors present on cells throughout the body. HGH functions to regulate body composition, fluid homeostasis, glucose and lipid metabolism, skeletal muscle and bone growth, and possibly cardiac functioning. Sleep, exercise, and stress all increase the secretion of HGH.

The use of HGH is associated with several adverse effects including edema, carpal tunnel syndrome, joint pain, muscle pain, and abnormal skin sensations (e.g., numbness and tingling). It may also increase the growth of preexisting malignant cells, and increase the possibility of developing diabetes.

HGH is administered by subcutaneous or intramuscular injection. The circulating half-life of HGH is relatively short half-life (20-30 minutes), while its biological half-life is much longer (9-17 hours) due to its indirect effects.

Human growth hormone is illicitly used as an anti-aging agent, to improve athletic performance, and for bodybuilding purposes. It is marketed, distributed, and illegally prescribed off-label to aging adults to replenish declining hGH levels and reverse age-related bodily deterioration. It is also abused for its ability to alter body composition by reducing body fat and increasing skeletal muscle mass. It is often used in combination with other performance enhancing drugs, such as anabolic steroids. Athletes also use it to improve their athletic performance, although the ability of HGH to increase athletic performance is debatable.

Athletes, bodybuilders, and aging adults are the primary abusers of HGH. Because the illicit use of synthetic HGH is difficult to detect, its use in sports is believed to be widespread. Over the past few years, numerous professional athletes have admitted to using HGH. Bodybuilders, as well as celebrities also purportedly use it for its ability to alter body composition. Aging adults looking to reverse the effects of aging are increasingly using synthetic HGH.

Hepatitis C and diagnosis with HIV

Hepatitis C is usually transmitted through blood-to-blood contact. Needles, syringes and other equipment used to inject drugs, and equipment used to sniff drugs such as straws or banknotes, should never be shared. The sexual transmission of hepatitis C is now an issue of concern. It used to be thought that this was very rare. However, there have been recent reports of increasing numbers of gay men testing positive for hepatitis C. Many of these men are HIV positive and their only risk activity appears to be unprotected anal sex. Sexual activity that carries a risk of contact with blood, such as rougher anal sex, use of sex toys and fisting, seems to have a particular risk of hepatitis C transmission. Group sex, especially in the context of drug use, is also an important risk factor. Using condoms correctly, every time you have sex, not sharing sex toys or washing them between use, and not sharing pots of lubricant can reduce the risk. Mother-to-baby transmission of hepatitis C is thought to be uncommon, but the risk is increased if the mother is also HIV positive. A high hepatitis C viral load increases the risk that a mother will pass on hepatitis C to her baby and, as with HIV, a caesarean delivery reduces the risk. It’s best not to share razors, hair and nail clippers, nail scissors or toothbrushes if you have hepatitis C.

Very few people experience symptoms when they are first infected with hepatitis C. When they do occur, symptoms include jaundice, diarrhoea and feeling sick. In the longer term, about 50% of people with hepatitis C will experience some symptoms. The most common ones are feeling generally unwell, extreme tiredness, weight loss, depression and intolerance of fatty food and alcohol. Although a small proportion of people infected with hepatitis C clear the infection naturally, about 85% will go on to develop chronic hepatitis C. About a third of people will develop severe liver disease within 15 to 25 years. The severity of disease can be affected by the strain of hepatitis C you are infected with. Men, people who drink alcohol, people who are infected with hepatitis C when they are already into middle age, and people with HIV seem to experience faster hepatitis C disease progression. Hepatitis C can cause liver fibrosis (hardening) and cirrhosis (scarring). This damages the liver to such an extent that it cannot work properly, causing jaundice, internal bleeding and swelling of the abdomen. Chronic infection with hepatitis C can cause liver cancer (hepatocellular carcinoma, or HCC). HCC is especially likely to happen in people with cirrhosis, particularly if they drink heavily. There’s also some evidence that smoking can speed up the rate of cirrhosis and increase the risk of liver cancer. Surgery is the most effective form of treatment for liver cancer, but  other options include chemotherapy and treatment with drugs.

You should be tested soon after your diagnosis with HIV to see if you are also infected with hepatitis C. Unlike hepatitis B, there is no vaccine against hepatitis C. If you are in a group at high risk of infection with hepatitis C, it’s recommended that you have regular tests to see if you have been infected. A test is available to measure hepatitis C viral load. Unlike the HIV viral load test, this is not an indicator of when to start treatment. However, it is used to show how effective treatment any hepatitis C is being and how long it should continue. Liver function tests can give an indication of the extent to which hepatitis C has damaged your liver. Liver ultrasounds and biopsies may also be used. People co-infected with HIV and hepatitis C are more likely to develop liver damage than people who are only infected with hepatitis C. However, hepatitis C does not increase your risk of becoming ill due to HIV or responding less well to HIV treatment.

HIV treatment can be used safely and effectively if you are co-infected with HIV and hepatitis C. HIV treatment that suppresses viral load and increases your CD4 cell count can slow the rate of HCV-related liver damage. However, you may be at greater risk of experiencing the liver side-effects which some anti-HIV drugs can cause, and you and your doctor should have this in mind when selecting which anti-HIV drugs to take. It also seems to be the case that people co-infected with HIV and hepatitis C are at greater risk of developing some of the metabolic disorders which anti-HIV drugs can cause (particularly insulin resistance and diabetes). Drugs are available for the treatment of hepatitis C and you should receive your treatment and care from doctors who are expert in the treatment of both HIV and hepatitis C. This may mean that, as well as seeing an HIV doctor, you also need to see a specialist liver doctor.

If you have both HIV and hepatitis C, you should be assessed to see if you would benefit from starting hepatitis C treatment.

If you and your doctor decide that you will start hepatitis C treatment now, and your CD4 cell count is between 350 and 500, you should start hepatitis C treatment first, then start HIV treatment. If your CD4 cell count is between 350 and 500 and you don’t yet need treatment for hepatitis C, you should start HIV treatment.

If your CD4 cell count is under 350, you should start HIV treatment before starting hepatitis C treatment. A number of anti-HIV drugs have interactions with drugs used to treat hepatitis C. The choice of anti-HIV drugs you take will need to be made with these possible interactions in mind.

Before you start treatment for hepatitis C, it is important to know which strain, or genotype, of hepatitis C you have been infected with, as this can predict your response to treatment and the amount of time you will need to take treatment for. There are several hepatitis C genotypes. Type 1 is most common in the UK, and unfortunately responds least well to the currently available treatments for hepatitis C. Genotype 4 is also harder to treat. People with genotypes 2 or 3 respond better to treatment. However, there are new HCV drugs available, and more in development, which should improve the chances of a cure for people with harder-to-treat genotypes.

Factors such as your age, gender, how long you have had hepatitis C, the degree of liver damage and whether cirrhosis has developed are also important in predicting if treatment is likely to be effective. Unlike HIV treatment, treatment for hepatitis C is not lifelong. It consists of 24 or 48 weeks of treatment, and the length of treatment you receive will depend on the hepatitis C genotype you are infected with. A test after twelve weeks of treatment can predict if you are going to respond to treatment.

Drugs are available for the treatment of hepatitis C. The backbone of treatment consists is pegylated interferon and ribavirin. These are taken in combination with an anti-HCV protease inhibitor. This sort of triple combination has been found to be much more effective than dual therapy with pegylated interferon and ribavirin alone. The aim of hepatitis C treatment is to eradicate infection with hepatitis C completely.

Other aims of treatment include normalizing liver function, reducing liver inflammation and reducing further damage to the liver. If you are ill because of HIV, then the aim of hepatitis C treatment is likely to focus on improving your tolerance of anti-HIV drugs, reducing the risk of death from liver problems and improving your overall quality of life. Hepatitis C treatment can have unpleasant side-effects, including a high temperature, joint pain, weight loss, nausea and vomiting and depression. Other side-effects include disturbances in blood chemistry.

Steroid Injecting Bodybuilders At High Risk Of HIV Infection

The medical observer Australia has reported an alarming increase of HIV infection with 1 in 10 steroid users having evidence of infection with either HIV, Hepatitis B and C. In Australia, education for recreational drug users on safe use of needles has lead to a dramatic decrease in HIV and Hepatitis infections. Many anabolic steroid and injectable tanning product users do not identify as “recreational users” so may miss the important messages about using clean needles. If you are a steroid user it’s vital to remember the importance of using clean needles for every injection and to never share equipment. HIV stands for human immunodeficiency virus. This virus, when transmitted into the human body, causes HIV infection, which is known to destroy the complete immune system of the person. This makes the body susceptible to illness and thus it gets very difficult to fight off the infection. Eventually, the last stage of HIV infection is AIDS.

The HIV can spread in three ways:

Contaminated Blood transfer
Intimate sexual relations
Use of syringes and needles that are contaminated.

The HIV could also spread to the baby from an infected pregnant woman. People with HIV infection show no symptoms even up to 10 years of being infected; however, they can pass the virus on to others during this period. The HIV Western blot tests and HIV ELISA detect antibodies in the blood. These antibodies work against the virus. If there are antibodies present in the blood stream, it indicates that you are body has the HIV virus within it. In the event of the test being negative, the presence of the antibodies is also negated and it would mean that you are not infected with HIV. However, you will have to take the test once again in three months. If the HIV western blot tests and HIV ELISA then show positive, it means that there are antibodies present in your blood stream. At this point, further tests must be done to determine the level of HIV present in the bloodstream. For the treatment of HIV infection, doctors recommend drug therapy. However this is for patients who have been taking their medications regularly and have a CD4 count of below 500 cells/mL. Some people, such as pregnant women and people with kidney problems caused by HIV may need to go through treatment regardless of their CD4 count.

It is very important that people with HIV take all doses of their medications. If they don’t, the virus will become resistant to the drugs. There are various types of anti-viral drugs used in therapy. In infected pregnant women, treatment is done to reduce the chances of transmitting the virus to the baby.

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 favorable. 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. 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 (AS) 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.

Non-HIV-related illnesses – hepatitis
    Hepatitis B
    Hepatitis C
    Liver transplants
    Hepatitis A

Hepatitis means inflammation of the liver. The liver is the largest internal organ in your body. It is located at the upper right-hand side of the abdomen. Having a healthy liver is important for everybody, but it is especially important for people with HIV. The liver plays a vital part in processing medicines used to treat HIV and other conditions. Viral infections that affect the liver, such as hepatitis A, hepatitis B and hepatitis C, can make you ill and also mean that the liver is unable to process medicines properly.

Co-infection with hepatitis B virus or/and hepatitis C virus is increasingly becoming a cause of illness in people with HIV. Both these viruses affect the liver, can make you very ill and can be fatal. However, it is also possible to recover from these conditions spontaneously, and for them to be treated. Hepatitis B virus (often known as HBV) is common in some of the communities affected by HIV in the UK, as it can be contracted in the same ways as HIV, particularly through contact with blood, semen or vaginal fluid, and from mother to baby. It is possible to clear HBV without treatment, through the response of the immune system. If this does not happen (which is the case for about 10% of people), the infection can remain for many years and become ‘chronic’. People with HIV are more likely to develop chronic hepatitis B. HBV can cause severe or even fatal damage to the liver. Long-term infection with hepatitis B can cause liver cancer, and rates of liver cancer in people with HIV are elevated because of hepatitis B and hepatitis C. However, you may not have any symptoms at all for many years. During this time, it is still possible to pass HBV on to others. Using condoms correctly, every time you have sex, can protect against hepatitis B if you have a detectable HBV viral load. HBV can also be passed on through saliva, unlike HIV. You should be tested soon after your HIV diagnosis for hepatitis B, to see if you have been infected with the virus. If you have had a previous infection, and have recovered from it, you will then be immune to HBV. A vaccine is available to protect you against hepatitis B. If you don’t have the virus, and a test shows that you do not have natural immunity against it, it is recommended you are vaccinated against it. It is now recommended that all people with HIV, who have never had HBV, should have an annual test to check their immunity levels and be offered a booster vaccine if their immunity level has dropped below protective levels since their last vaccine. Your regular HIV monitoring involves checking the health of your liver. If you are co-infected with hepatitis B, this becomes even more important. Your healthcare team will regularly monitor your liver function using blood tests. Ultrasound examinations may also be performed, particularly if your liver shows signs of damage. Treatments are available for hepatitis B. These include antiviral drugs such as  adefovir (Hepsera) and interferon alpha. Some  anti-HIV drugs also work against hepatitis B. These are 3TC (lamivudine, known as Zeffix when used to treat hepatitis B and Epivir when used to treat HIV), tenofovir (Viread) and FTC (emtricitabine, Emtriva). Tenofovir and FTC are available in a combined pill called Truvada. There is conflicting evidence about the impact of hepatitis B on the progression of HIV disease. Anti-HIV drugs can be used safely and effectively in people with hepatitis B. However, when some people start HIV treatment, they experience a short-term flare-up of hepatitis B. This is because the immune system is getting stronger and is fighting hepatitis B. Some doctors try to stop these flare-ups happening by starting treatment for HIV and hepatitis B at the same time. Because of the risk of developing drug resistance, you should only take anti-HIV drugs that are effective against hepatitis B as part of an HIV treatment regimen. Nor should you take adefovir unless you are taking HIV treatment because of a risk of resistance.  If you are going to take treatment just for hepatitis B (and not for HIV), you should take interferon alpha. Which drugs you are treated with will depend on your CD4 cell count and whether you already need HIV treatment.

Muscle Pain or Myositis in HIV-infected persons

HIV-infected patients may present with muscle pains. It is important to examine

Muscle problems in HIV-infected persons include idiopathic polymyositis, polymyositis secondary to AZT toxicity, and pyomyositis. Weakness in the shoulder or hip girdle muscles, along with an elevated level of creatine phosphokinase (CPK) or aldolase or both, suggests polymyositis. AZT-induced polymyositis is similar to the idiopathic form, with muscle weakness, elevated CPK levels, and on muscle biopsy, myofibril necrosis with scant inflammation. In most cases, the patient improves gradually when AZT is discontinued, and the CPK level returns to normal.

Pyomyositis refers to solitary or multiple muscle abscesses that are not formed by local extension from superficial subcutaneous tissue. Although originally reported only in tropical climates, a number of cases were more recently described recently in North America, usually in healthy subjects but also in immune compromised hosts. The quadriceps muscle is most commonly involved, and 75% of patients have a single abscess.

Patients present initially with fever, and localized muscle pain. If the abscess is not deep in the muscle, redness, swelling, and a gradually developing woody induration may occur. If a painful area is found in a muscle during a physical examination, ultrasound, computed tomography, or magnetic resonance imaging is helpful in identifying and localizing the abscess or abscesses and in providing guidance during needle aspiration for identification of the pathogenic organism. S. aureus is responsible for the infection in the majority of cases, although a number of other bacteria have been recovered, including Escherichia coli and Salmonella enteritidis. After the area of the infection is defined, a diagnostic aspiration of the mass can be done under ultrasonic guidance. Systemic antibiotics usually cure a single small abscess, but large or multiple loculated abscesses often require surgical incision and drainage. Psoriatic arthritis with or without psoriasis occurs in HIV-infected persons. The prevalence of psoriasiform skin changes and psoriatic arthritis in HIV-infected persons probably is the same as that in non-HIV infected persons (1 to 2%), but the severity of the HIV-associated psoriasis and psoriatic arthritis tends to be worse. The foot and ankle are the most common, as well as the most severe, sites of inflammation in HIV-infected patients with psoriatic-like arthritis. Intense enthesopathy and dactylitis, especially in the feet, usually accompany the arthritis. The enthesopathy can be a major cause of disability. Frank synovitis and synovial effusions are less common, but can occur at the ankle and subtalar, metatarsal phalangeal, and interphalangeal joints of the feet. Sacroiliac and spine involvement may also occur. The radiologic appearance of these joints may mimic classic psoriatic arthritis, with "pencil and cup" deformities and osteolysis, even in the absence of frank psoriasis.

Nail involvement is a common presenting symptom of arthritis, especially in the distal interphalangeal joints of the hands and feet. Many patients with psoriatic skin manifestations or onycholysis have only these musculoskeletal findings and do not meet the criteria for a diagnosis of psoriatic arthritis. Nail involvement occurs in most patients who present with inflammatory articular symptoms. There is a high clinical correlation between skin and joint involvement, and joints may develop erosive changes and crippling deformities. Patients with HIV infection and psoriatic arthritis fall into one of two patterns of disease: either the articular disease is sustained and aggressive, progressing to joint erosions, or it is characterized by mild and intermittent joint involvement.
It is unknown whether HIV-associated psoriatic syndromes are strictly analogous to idiopathic psoriatic arthritis in non-HIV infected patients. Evidence against this possibility is that none of the human leukocyte antigen (HLA) alleles found in patients with idiopathic (non-HIV) psoriasis vulgaris or psoriatic arthritis (such as Cw6, B13, or B17) occur with greater frequency among HIV-infected patients with psoriatic-like arthritis.
The treatment of spondyloarthropathy in HIV-infected patients is similar to that for non-HIV infected patients. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin (75 to 150 mg per day), can be used initially for the joint symptoms, but results have been disappointing. There are few data on second-line agents such as gold, methotrexate, and azathioprine. There are reports that phenylbutazone (100 mg 3 times per day) is an effective drug for this arthritis, and neutropenia has not been a problem even in patients receiving AZT concurrently.

Patients in whom psoriatic skin or joint disease does not respond to NSAIDs may be treated with phenylbutazone (100 mg 3 times a day) or sulfasalazine (1 to 2 g per day). Etretinate may also be helpful. The use of psoralen and pulsed UV actinotherapy (PUVA) has helped the skin and joints of some HIV-infected individuals with psoriatic arthritis.

At our institution, treatment of patients with severe arthritis with low doses of methotrexate (5 to 10 mg per week) has led to rapid (< 4 weeks) improvement in inflammatory joint symptoms as well as improvement in skin lesions. Methotrexate can be given until the skin and joint disease is under control, then slowly tapered by 2.5 mg per month, aiming for a maintenance dose of 5 mg per week. Patients must be monitored closely, because there are anecdotal reports of progressive immunodeficiency and opportunistic infections in HIV-infected individuals with Reiter's syndrome who are treated with methotrexate. Systemic glucocorticoid use is generally discouraged because of increased risk of infection, but intra-articular steroid injection (every 4 to 6 months) may provide substantial relief to individual arthritic joints.
the patient to determine whether weakness accompanies the pain, and whether the pain is generalized or localized to one muscle group; localized pain may be a sign of polymyositis, whereas generalized pain suggests a systemic process. It is also important to determine whether the patient is taking zidovudine (AZT), and whether the muscle pain began soon after initiation of the drug therapy.