IAC: Growth Hormone Eases HIV-Treatment Spawn Lipodystrophy

TORONTO -- Human growth hormone appears to reverse some elements of HIV-treatment related lipodystrophy, researchers reported here.

A 12-week induction treatment followed by 24 weeks of maintenance therapy resulted in:

• Reductions in visceral adipose tissue.
• Reductions in truncal fat.
• Reductions in non-high density lipoprotein cholesterol.

"The disease and its treatment tend to impose a double whammy on patients with the HIV virus infection," said Carl Grunfeld, M.D., of the University of California San Francisco, in a late-breaking oral presentation at the 16^th International AIDS Conference here.

"Excess accumulation of truncal fat, including visceral adipose tissue, in HIV-infected persons, is associated with risks to health and psychosocial well-being," Dr. Grunfeld said. "No therapies are currently approved to treat this problem in HIV-infected individuals."

Dr. Grunfeld and colleagues enrolled 325 patients in a double-blind, placebo controlled trail. They assigned 241 patients to 4 mg of growth hormone in a daily dose for 12 weeks. Then this treatment group was divided into a maintenance treatment cohort of 92 patients who continued to receive 2 mg of growth hormone on alternate days for an additional 24 weeks. Of those who received the induction dose of growth hormone, another group of 93 patients were assigned to receive placebo for the remaining 24 week of the study.

The original placebo group of 81 patients was whittled to 73 patients for the second stage of the trial. They were continued on placebo every other day for the first two weeks but in the second two weeks, they received 4 mg of growth hormone daily.

In the primary endpoint of the trial, visceral adipose tissue at 12 weeks, those on growth hormone achieved a 20% fall in adipose tissue compared with a 4% gain in visceral adipose tissue among patients on placebo.

Dr. Grunfeld said that the difference reached statistical significance at the P<0.001 level. There was also a 7% decline in subcutaneous fat in patients on growth hormone, compared with a 2% rise in subcutaneous fat in the placebo patients, a difference that was also statistically significant.

Truncal fat also declined about 20% in patients on human growth hormone, Dr. Grunfeld said, compared with a 2% gain in placebo patients. Subcutaneous limb fall fell about 5% with growth hormone administration while limb fat increased about 3% in patients on placebo. He said the differences were statistically significant at the P<0.001 level.

LDLs declined about 7% from baseline among those on active treatment compared with a decline of 3% from baseline. The changes in baseline measurements were significant, he said, but the differences between the groups were not significant. Non-HDL-cholesterol declined 5% in the treatment groups, but just 1% in the placebo patients. That was statistically significant at the P=0.018 level, he said.

HDL levels rose about 2% for those on treatment, but barely budged from baseline for those on placebo. That difference also proved to be significantly different at the P<0.001 level, Dr. Grunfeld said.

In the maintenance phase of the trial, he noted that less than half the patients on the lower dose of growth hormone regained more than half the visceral adipose tissue lost during the induction phase of the trial.

"Adverse effects were mostly mild to moderate," Dr. Grunfeld said. He also noted transient increases in parameters of insulin processing.

"The results are interesting and intriguing," commented Daniel Kuritzkes, M.D., director of the AIDS research clinic at Brigham and Women's Hospital in Boston. Dr. Kuritzkes said the success of treatment of body fat with growth hormone, while still controversial, might actually point to future treatment of central obesity, even in those who do not have HIV.

"I certainly am not saying that we should use this drug for that purpose," he said, "but suggested that it might be something that deserves further research." He also suggested that growth hormone for treatment of lipodystrophy requires addition study before it can be recommended.

Dr. Grunfeld's study was sponsored by Serono, a marketer of recombinant human growth hormone.