MELBOURNE, Australia -- HIV-infected patients treated with a growth hormone releasing hormone analog achieved modest reductions in abdominal and liver fat, researchers said.
In a preliminary study that involved 54 patients, treatment with tesamorelin (Egrifta) reduced visceral adipose tissue 34 cm2 compared with a reduction of 8 cm2 achieved by patients on placebo (P=0.005), reported of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues, at the International AIDS Conference.
The results were also published simultaneously in the .
They found the median change in lipid to water percentage -- a marker of liver fat -- was reduced by 2% in the patients on tesamorelin compared with a 0.9% increase among the placebo patients (P=0.003).
"Tesamorelin's ability to reduce liver fat in conjunction with the reduction of abdominal fat may be clinically important for patients with HIV infection who have fatty liver disease along with increased abdominal fat," Grinspoon said.
"While some patients with nonalcoholic fatty liver disease have a benign course, others may develop a more serious condition involving liver inflammation, cellular damage, and fibrosis, which can progress to cirrhosis and end-stage liver disease or to liver cancer," he added.
Tesamorelin is the only FDA drug approved for the intended reduction of abdominal fat deposits that develop in some patients receiving antiviral therapy for HIV infection. It stimulates the body's release of growth hormone, which is reduced in HIV lipodystrophy.
Lipodystrophy, an abnormal abdominal fat accumulation, develops in 20% to 30% of patients receiving antiretroviral drugs. About 30% to 40% of people living with HIV develop nonalcoholic fatty liver disease, but not necessarily in conjunction with lipodystrophy.
"Although abdominal hypertrophy may be less common with newer antiretroviral therapy, there exists a substantial group of patients with abdominal fat accumulation in the context of long-term prior antiretroviral therapy," the researchers noted.
"In human immunodeficiency virus infection, abdominal fat accumulation is associated with ectopic fat accumulation in the liver. To date, there are no approved pharmacologic strategies to reduce liver fat," the authors added.
Lead author , also from Harvard Medical School, noted that tesamorelin specifically targets abdominal fat reduction but its effects on liver fat were unknown.
"Our population was primarily male and had been living with HIV and receiving antiretroviral therapy for a long period, consistent with many patients exhibiting lipodystrophic changes in fat," Grinspoon added.
The researchers screened 76 persons, randomizing 54 individuals who met the inclusion criteria. Of that group, 26 were assigned to the placebo group and 28 were randomized to receive tesamorelin.
Participants in the study were injected subcutaneously daily for 6 months with either tesamorelin (2 mg/day) or placebo.
Because growth hormone treatment can lead to increased blood sugar levels and reduced insulin sensitivity, about half of the subjects in each group also underwent procedures to analyze insulin secretion and insulin resistance.
A 3-month follow up was attended by 20 placebo patients and 25 patients who had been assigned tesamorelin. A 6-month visit was attended by 20 patients on placebo and 23 on tesamorelin. The available data analysis included the patients who attended the 6-month follow up.
The assessments also included comprehensive measures of factors related to HIV infection, lipid and glucose metabolism, along with analysis of abdominal fat by CT scan and of liver fat by MR spectroscopy.
Studies at baseline and at the end of the 6-month study period indicated there did not appear to be long-term statistically significant differences in the insulin studies, the researchers reported.
Although tesamorelin treatment did appear to have reduced insulin sensitivity and raised blood sugar levels at the 3-month assessment, by 6 months both measures had returned to levels observed at the study's outset, implying that the drug's impact on glucose metabolism was only temporary, Stanley said.
"Tesamorelin's neutral long-term effects on insulin sensitivity and glucose are important, since HIV patients with abdominal fat accumulation may have underlying insulin resistance; it's important to know that won't be worsened by this treatment," Grinspoon explained. "Since we know that liver fat is associated with inflammation in the liver, reducing it may result in less inflammation."
He reported that liver enzyme tests for liver inflammation markers were lower among patients on tesamorelin.
The authors noted that widespread utilization of tesamorelin in HIV-infected patients with lipodystrophy could be limited because the drug is expensive, with some estimates reaching $3,000 a month.
They observed that their cohort was not specifically chosen for increased liver fat, and that because the absolute change in lipid to water percentage was modest, the clinical significance of their data is not known. In addition, liver biopsies -- the gold standard for assessing features of steatohepatitis and advanced liver disease -- were not performed.
The researchers also did not collect data after discontinuation of tesamorelin.
"Previous studies have shown that visceral fat may reaccumulate after discontinuation of tesamorelin, and future studies will be necessary to determine if reductions in liver fat with tesamorelin are maintained following treatment discontinuation," they wrote.
Disclosures
Grinspoon disclosed relevant relationships with Aileron Therapeutics, Ferrer, sanofi-aventis, Navidea, AstraZeneca, EMD Serono, Theratechnologies, Bristol-Myers Squibb, Gilead, Amgen/Immunex, Novo Nordisk.
Primary Source
Journal of the American Medical Association
Stanley T, et al "Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial" JAMA 2014; 312: 380-389.