Increasing the body's production of growth hormone may be an effective treatment for HIV lipodystrophy, a syndrome involving the redistribution of fat and other metabolic changes in those receiving combination drug therapy for HIV infection.
Researchers from Massachusetts General Hospital have reported that administration of growth-hormone-releasing hormone to a group of men with HIV lipodystrophy significantly improved fat distribution with no negative side effects. The study appears in the July 14 Journal of the American Medical Association, a special HIV/AIDS issue published in conjunction with the International AIDS Conference in Bangkok.
"This study is an initial proof of principal that augmenting low growth hormone levels in this way has the potential to reverse the abnormal body composition seen in these individuals," says Steven Grinspoon, MD, of the MGH Neuroendocrine Unit and Program in Nutritional Metabolism, the report's senior author. "At the current time, there is no established treatment for this syndrome."
The combination drug strategy known as highly active antiretroviral therapy (HAART) can significantly reduce virus levels and help maintain health in HIV-infected individuals, but more than half may develop lipodystrophy. Typical symptoms of the syndrome include a loss of subcutaneous fat in the face, arms, and legs and increased fat deposits in the abdomen and upper back. The metabolic aspects of the syndrome – changes in cholesterol and other blood lipids, and development of insulin resistance – could also increase the risk of cardiovascular disease.
It recently has been discovered that men with lipodystrophy do not secrete normal levels of growth hormone. Although growth-hormone (GH) injections can reduce fat deposits that develop in other GH-deficiency situations, high-dose injections have a number of significant side effects, including insulin resistance, already a problem for lipodystrophy patients.
In a healthy body, secretion of GH is controlled by a feedback mechanism, which shuts down the process if hormone concentrations exceed normal blood levels. Directly injecting GH could bypass this natural control mechanism, allowing blood levels to rise too high. In an attempt to raise GH levels in a more natural manner, the MGH team devised a strategy using growth-hormone-releasing hormone (GHRH).
They enrolled 31 men with HIV lipodystrophy for a 12-week, randomized, double-blinded study. Participants injected themselves twice daily with either GHRH or a placebo injection. To track GH secretion, the researchers measured blood levels of insulin-like growth factor-1 (IGF-1). As part of the natural feedback system, IGF-1 levels rise in response to GH blood levels, which turns off further hormone secretion. Body composition was measured by x-ray and CT scan studies, and blood tests followed other metabolic markers.