A Canadian company, Theratechnologies, believes it may have developed a treatment that can reduce the abdominal fat accumulation seen in HIV-positive people who develop lipodystrophy. In a press release issued on April 15th, the company said that results of a randomised phase II clinical trial showed that its recombinant human growth hormone releasing factor (ThGRF) was associated with a significant reduction in visceral fat without the negative effects on glucose control seen with human growth hormone treatment.
Body fat changes in people with HIV who receive antiretroviral treatment follow several patterns:
- Fat loss from the limbs (argued by some researchers to be the only feature of lipodystrophy that distinguishes the syndrome from body fat changes that occur with aging)
- Central fat accumulation in the abdomen (not considered to be distinctive of lipodystrophy at a population level, but rapidly emergent in some patients after commencing protease inhibitor-containing regimens and viewed by most patients as drug-related)
- A mixture of the two patterns
Treatment for fat redistribution has been largely unsuccessful, with human growth hormone the only treatment showing any effect on central fat accumulation. However, blood glucose levels tend to increase after human growth hormone treatment because it can over-ride the body’s natural regulation of glucose levels. It is also expensive and its effects can be reversed if the treatment stops.
Rather than introducing recombinant human growth hormone into the body, the Theratechnologies study used a product which stimulates the body’s own production of human growth hormone, in the hope that this would not disrupt the mechanism by which growth hormone levels regulate blood glucose levels.
The study recruited 61 individuals, predominantly male (89%), who were randomly assigned to receive a daily subcutaneous injection of 1 mg of ThGRF, 2 mg or placebo for 12 weeks. At baseline, all patients had lipodystrophy as a result of antiretroviral treatment. Their average body mass index (BMI) was 28 kg/m2, their mean waist circumference 101 cm and their mean waist/hip ratio 1.0.
At a dose of 2mg per day, body fat was preferentially lost at the trunk level (-1.1 kg, p less than 0.02 vs placebo), with no significant change in limb fat.
Within the trunk, this fat loss took place solely in the visceral compartment (VAT, -15.7%, p less than 0.05 vs baseline, NS vs placebo; placebo: -5.4%, NS vs baseline). Longer term follow-up in a larger patient group will be needed to clarify whether visceral fat loss is significant when compared to placebo.
ThGRF did not reduce subcutaneous fat levels either in the abdomen or in the limbs.
"The results of this study are important and suggest ThGRF as a potentially beneficial treatment for HIV-associated lipodystrophy," said Dr. Steven Grinspoon, Director of the Program in Nutritional Metabolism at Harvard Medical School and lead investigator for the US.
Theratechnologies now plans to go through with a larger phase III study in order to seek registration for lipodystrophy treatment.