Treatment with tesamorelin significantly improves visceral fat accumulation in patients with HIV, an international team of investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.
Preliminary results of the study were reported at the 2008 International AIDS Conference in Mexico City.
The results of a 26-week study, followed by a further six months of analysis, showed that therapy with the drug reduced levels of visceral fat and waist circumference without having detrimental metabolic effects.
Tesamorelin was also shown to be safe, although a small number of patients discontinued therapy because of mild hypersensitivity reactions.
“With these new data, there are now consistent results from two large Phase III, randomised, placebo-controlled studies to suggest that [tesamorelin] is a potentially useful clinical strategy to selectively reduce visceral adipose tissue and improve body image among HIV-infected patients with abdominal fat accumulation in the context of antiretroviral therapy”, comment the researchers.
Some HIV-positive patients have developed changes in body fat composition whilst taking antiretroviral therapy. This can include fat accumulation, fat loss, or both.
In many patients this has involved the accumulation of central visceral fat and the loss of sub-cutaneous fat.
Abdominal, visceral fat gain is strongly associated with increased blood lipids and insulin resistance, both of which can increase the risk of cardiovascular disease. In HIV-negative patients, increased waist circumference has been associated with an increased risk of death, and cardiovascular disease is now a major cause of illness and death in patients with HIV.
Therefore, reducing abdominal visceral fat accumulations could have metabolic benefits for patients taking antiretroviral therapy.
Body fat changes can also be highly distressing and stigmatising, therefore remedying them could help improve self-image and the general wellbeing of patients with HIV.
Growth hormone secretion is reduced in HIV-positive patients with visceral fat accumulation. Tesamorelin is a growth hormone-releasing factor, and investigators wished to see if it is a safe and effective treatment for HIV-positive patients with central, visceral fat accumulation.
Study design
They therefore designed a six-month, placebo-controlled study involving adult HIV-positive patients with this condition. They were randomised on a two-to-one basis to receive either tesamorelin or a placebo.
Changes in body composition were assessed using both CT and DEXA scans and regular blood samples were taken to assess metabolic parameters. Both the patients and their physicians completed questionnaires about perceived changes in “belly size” and “belly image distress”.
The study also involved a six-month continuation phase. This was designed to obtain further information on the safety of the drug, and to see what its longer-term efficacy was. The patients who initially received the placebo were switched to tesamorelin. The individuals who received the drug in the first phase of the study were equally randomised to continue taking it or to switch to a placebo.
A total of 404 patients were recruited to the study. Tesamorelin was given to 270, the remaining 126 receiving the placebo.
Visceral fat decreased by a mean of 11% in the tesamorelin group compared to only 0.6% in the placebo group, a highly significant difference (p < 0.001).
There was a mean 1kg fall in trunk fat amongst the individuals treated with tesamorelin compared to a mean reduction of 0.2kg in the patients who received the placebo (p < 0.001).
Therapy with tesamorelin also produced significantly greater improvements in hip-to-waist ratio (p < 0.001) and gains in lean body mass (p < 0.001) than the placebo.
Importantly, tesamorelin did not affect levels of sub-cutaneous fat.
Although the drug increased the release of insulin-like growth factor-1 (p < 0.001), it did not have a detrimental effect on lipid levels or the glucose metabolism.
Both the patients' and physicians' perceptions of belly image improved more in the tesamorelin group than the placebo arm of the study.
The number of discontinuations was equal in both arms of the study (25%).
Safety extension
By the end of the six-month extension phase of the study, there was a 17.5% reduction in visceral abdominal tissue amongst the patients who continued to take tesamorelin compared to a 1% reduction in the individuals switched to the placebo (p < 0.001). This indicated that improvements in central visceral fat accumulation were not sustained after therapy with the drug was discontinued, but that visceral fat reduction did continue if tesamorelin treatment continued.
Similar patterns were also seen in other measures of body composition, with the exception of waist circumference. This measure decreased by 3.8 cm from baseline in the treatment arm and 2.4 cm in the placebo arm.
No significant changes in glucose metabolism were associated with tesamorelin. But compared to baseline, those who received the drug had significantly lower total cholesterol than patients taking the placebo (p < 0.05).
Tesamorelin remained associated with improved perception of body image by both the patients and their doctors. In addition, the patients switched to the placebo also rated their body image more highly.
Similar rates of treatment discontinuation were seen in the two arms of the study.
However, up to 4% of patients receiving tesamorelin experienced a localised hypersensitivity reaction near the site where the drug was injected. “For such patients”, write the investigators, “treatment discontinuation is prudent”.
They conclude, “in this study, we demonstrate that tesamorelin significantly improves body composition…these benefits occurred without any significant increases in glucose or insulin levels.”
Tesamorelin's manufacturer, the Canadian biotechnology company Theratechnologies, is currently awaiting US Food and Drug Administration review of the product (to be marketed as Egrifta), expected before the end of March. Tesamorelin will be marketed in the United States by Serono.
Falutz J et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomised placebo-controlled trial with a safety extension. J Acquir Immune Defic Syndr, advance online publication, 2010.