Friday February 22 2008
HIV targets T-cells in the immune system
A new growth hormone therapy helps boost the immune system of HIV patients, reports The Guardian today. The newspaper goes on to say that the treatment “doubled the number of immune cells HIV patients had circulating in their blood, suggesting it was rebuilding their ailing immune systems”.
The newspaper report is based on a small American study that treated 22 HIV patients and monitored their progress over two years. In this particular group of people, growth hormone seems to increase the levels of circulating CD4+ T-cells, which are important for immune function. However, it isn’t possible to apply the results of this study to other people, the research needs to be extended and any benefits need to be weighed up against the damaging effects of the treatment. Only then will it be clear whether growth hormone should be added to the armoury of treatments for people with HIV.
Where did the story come from?
Dr Laura Napolitano and colleagues from the Gladstone Institute of Virology and Immunology, San Francisco General Hospital and the University of California carried out this research. The study was funded in part by a grant from the National Institutes of Health in the USA. It was published in the peer-reviewed medical journal: The Journal of Clinical Investigation.
What kind of scientific study was this?
The study was a randomised crossover trial in 22 HIV-infected adults who were not blinded to the treatment they were receiving in this study. All had been taking anti-retroviral treatment for at least a year and this continued throughout the study. The researchers were interested in whether growth hormone had any effect on the production of T-cells by the thymus gland. T-cells are a group of white blood cells that play an important role in the immune system. HIV targets and destroys T-cells and when the cells reach a critical low level the person is susceptible to certain characteristic infections and is then defined as having AIDS. The activity of the thymus gland can be indicated by measuring the level of a by-product of T-cell production in the blood: circulating TREC (T-cell receptor excision DNA circles).
In this crossover study, participants were allocated to one year of treatment with growth hormone followed by one year of no treatment (control group), or to the opposite sequence. Growth hormone was delivered by daily injections for one year. The effect of the hormone on immune function was assessed by comparing the results of blood tests and scans between the treatment and control groups.
Participants visited the San Francisco General Hospital (SFGH) Clinical Research Centre (CRC) at the start of the study, at six months and 12 months for a scan of their thymus gland. Blood tests to measure the response of the immune system were performed every one to three months, with a measurement of the level of true T-cells being taken every six months.
The participants who received the control treatment underwent the same regular assessments so that a comparison could be made at the end of the study. In the second year, i.e. when the two groups swapped round, tests on the immune system were performed at three, six and 12 months after discontinuation of growth hormone treatment. There was also a repeat scan of the thymus gland at 24 months.
What were the results of the study?
The researchers found that at the end of the first year, treatment with the growth hormone led to an increase in the scanned mass of the thymus. At six months, measures of the level of TREC (T-cell receptor excision DNA circles) in the blood suggested that the increase in mass was due to an increase in production of T-cells. However, at 12 months, the difference between the groups in levels of TREC was not significant.
The growth hormone increased the proportion of CD4+ T-cells, but the treatment had no effect on other immune functions, e.g. natural killer cells, neutrophils, B-lymphocytes.
What interpretations did the researchers draw from these results?
The researchers conclude that their study suggests that immune-based therapies could ultimately be used to increase production of T-cells in people with immunodeficiencies.
What does the NHS Knowledge Service make of this study?
This small crossover study provides results that will be of interest to the medical and scientific communities. There are key points to bear in mind when interpreting the results:
- Growth hormone was given via an injection every day for one year. This method of administering treatment could mean that patients would be unlikely to stick to such a regimen.
- As the researchers note, people with high levels of circulating HIV virus in the blood (viraemia) were excluded at the beginning of the study, so the effects of this treatment on such people couldn’t be assessed. As such, the study cannot be generalised to people with different levels of virus as viraemia may interfere with the effects of growth hormone. As HIV was being optimally managed in all participants, it isn’t really clear if treatment with growth hormone led to additional clinical benefit.
- Importantly, 95% of people receiving growth hormone also experienced adverse effects including joint pain, accumulation of fluid in body tissues, carpal tunnel syndrome and problems with glucose metabolism. The costs, both financial and to the patient, of managing these must be weighed up against the benefits of treatment.
- Crossover studies should have a washout period before groups are switched. This is to allow the effects of treatment to diminish so that groups can be fairly compared at the end of treatment. This study did not have a washout period and researchers note that the growth hormone had effects on the immune system even after discontinuation. These continuing effects would affect the comparison between treatment and control after crossover and may have introduced bias as the groups would have shown fewer differences in the second year. However, the researchers performed analyses both before and after crossover, and found that the post-crossover results largely supported those before crossover.
Sir Muir Gray adds...
Growth hormone is a powerful chemical; mostly doing more good than harm.