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.
Let's look at each of the possible treatment benefits of rHGH in HIV in turn:
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 (Abrams 2001; Fisher 2001; Montano et al 2007).
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.
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 (2002) 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 (2003) 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+.
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.
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 (Koutkia et al 2005).
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.
- Napolitano et al (2002). Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone. AIDS 24; 16(8):1103-11
- The AIDS Clinical Trials Group (ACTG) (2001). Effect of therapeutic immunization with HIV type 1 recombinant glycoprotein 160 ImmunoAG vaccine in HIV-infected individuals with CD4+ T cell counts of >or=500 and 200-400/mm3 (AIDS Clinical Trials Group Study 246/946). AIDS Res Hum Retroviruses 10; 17(15):1371-8
- Napolitano (2003). Approaches to immune reconstitution in HIV infection. Top HIV Med 11(5):160-3
- N Imami et al (2006). Effects of Recombinant Human Growth Hormone on HIV-1-specific T-Cell Responses, Thymic Output and Proviral DNA in Patients on ART: 48-Week Follow-up. 13th CROI. Denver, CO. Abstract 495.
- Koutkia et al (2005). Effects of Growth Hormone-Releasing Hormone on Bone Turnover in Human Immunodeficiency Virus-Infected Men with Fat Accumulation. J. Clin. Endocrinol. Metab 90:2154-2160.
- Montano et al (2007). Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J. Clin. Endocrinol. Metab 92(7):2793-802.
- Abrams (2001). Use of androgens in patients who have HIV/AIDS: what we know about the effect of androgens on wasting and lipodystrophy. AIDS Read 11(3):149-56.
- Fisher (2001). Wasting and lipodystrophy in patients infected with HIV: a practical approach in clinical practice. AIDS Read 11(3):132-3, 137-40, 147.
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