Recombinant human growth hormone (rhGH) can reverse HIV-associated wasting in patients taking highly active antiretroviral therapy (HAART) and improve physical performance, according to a randomised controlled trial published in the online edition of the American Journal of Physiology - Endocrinology and Metabolism on 5th May.
The involuntary loss of body weight or ‘wasting’ seen in HIV-positive patients is caused by a loss of muscle. This can lead to falls in the capacity to carry out aerobic exercise. Although the incidence of wasting has fallen since the advent of HAART, it remains a problem in up to a third of patients taking antiretroviral therapy.
rhGH is an artificially produced version of a hormone that occurs naturally in the body. It has been tested as a treatment for HIV-associated wasting, showing beneficial effects on increasing lean body mass, reducing body fat and improving lipodystrophy.
Although it has also shown benefit in improving fitness, many of the tests used to assess physical performance have involved high intensity exercise. As it is unclear how these tests relate to day-to-day activity, researchers from the University of Toronto wished to measure the effect of rhGH on physical performance in tests that are less strenuous.
“The administration of rhGH to patients with HIV-associated wasting is followed by favourable changes in aerobic capacity and functional status, owing to rhGH anabolic action,” they conclude.
The researchers recruited 27 adult male patients taking HAART and with unintentional weight loss of 10% or more over the past year. Despite weight loss, the men had a mean body mass index of 23.1kg/m2, indicating that they still had body weights that were in the normal range relative to height at the start of the study.
The investigators randomised the men to two groups, with one self-administering daily injections of 6mg rhGH and the other injecting placebo for three months.
As this study was designed as a ‘cross-over’ trial, three months after the end of the first treatment period, the first group began a three-month course of placebo, while the second started to inject rhGH every day. As there was no effect of whether the patients received drug or placebo first, the investigators combined the results of the two parts of the trial in their analysis.
They used dual energy X-ray absorptiometry (DEXA) scans to measure the lean body mass of the patients. After three months of rhGH treatment, lean body mass improved significantly relative to placebo (mean 3.7 vs. 0.3kg; p
The effect on body mass was paralleled by an increase in the ventilatory threshold, a measure of the physical fitness of the patients based on the rate of oxygen uptake while walking on a treadmill. The researchers found that rhGH caused a significant improvement in ventilatory threshold relative to placebo (mean 17.6 vs. –5.9%; p
In contrast, maximal oxygen uptake, a measure of oxygen use during maximum intensity exercise, was not significantly affected by the hormone treatment. Instead, it remained at levels lower than would be expected for men from the general population with similar ages and weights.
The investigators went on to examine the patients’ physical performance in a simple walking task, measuring the distance travelled and the amount of work done over six minutes. Although distances were not affected by the hormone treatment, the amount of work done did increase significantly (mean 33.3 vs. 16.5kJ; p
The investigators also measured the changes in mood levels reported by the patients using the ‘Profile of Mood States’ and ‘Nottingham Health Profile’ scales. Although vigour, fatigue, energy and physical mobility did not differ significantly between patients taking rhGH and placebo, there were non-significant trends for these measures to improve.
In addition, they found a significant relationship between increased physical performance and reduced fatigue (p = 0.024). This suggests that use of the hormone could improve fatigue levels through an increased capacity for physical activity.
Despite the benefits of rhGH treatment in improving physical performance, the investigators warn that this treatment may have unpleasant side-effects, due to its additional effect on other hormones in the body. “Elevated concentrations of insulin-like growth factor-I are associated with an increased risk of common cancers”, they explain. “The balance of benefits and risks of rhGH supplementation in patients with HIV-associated wasting has not been fully delineated.”
“Caution should be exercised in the use of rhGH in these patients,” they warn.
Ten patients in the study also required a reduction in the hormone dose due to the side-effect of joint pain. “Our study is limited by the halving of dose, necessitated by arthralgias, in nearly a third of our patients,” they write. However, they point out that a beneficial effect of the hormone treatment was seen despite this dose reduction.
This study was funded in part by Serono, Inc., who manufacture the form of rhGH (Serostim) used by the investigators.
Esposito JG et al. Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting. Am J Physiol Endocrinol Metab, online edition, 2005.