Tesamorelin Promising in People With HIV and NAFLD

One of the known comorbidities of HIV is non-alcoholic fatty liver disease (NAFLD), a condition characterized by excess liver fat in the absence of any significant alcohol consumption. People with NAFLD often suffer from liver fibrosis, or scar tissue, which can impede liver function and lead to liver failure.

Antiretroviral therapy (ART) to treat HIV has been implicated in the development of excess abdominal fat, or lipodystrophy, which itself is a risk factor for NAFLD. Recognizing the threat that HIV and its treatment can present to the liver, scientists tested a hormone analogue known as tesamorelin and found that it reduced liver fat and prevented fibrosis progression in a population of HIV-positive patients.

A team of investigators at the National Institutes of Health (NIH) and Massachusetts General Hospital in Boston recruited 61 people living with HIV to take part in the study. All were adults and none were heavy drinkers. Each had a hepatic fat fraction (the percentage of the liver composed of fatty tissue) of at least 5%, above average. The participants were randomized in a 1:1 ratio to receive either the standard dose of 2 mg daily of tesamorelin or to receive a placebo daily. After 1 year of receiving either tesamorelin or a placebo, all participants received tesamorelin for 6 months.

The investigators found that 35% of participants on tesamorelin were able to lower their hepatic fat fraction to normal range, while just 4% of those in the placebo group managed the same. Just 2 people in the tesamorelin arm of the study saw their fibrosis progress, while 9 in the placebo group experienced that outcome. The study team also noted that certain blood markers for liver damage and inflammation went down more in the tesamorelin group.

Although newer ART regimens do not result in lipodystrophy, patients who took older ART medications may still suffer the effects. “Patients who have previously received older ART and have lipodystrophy often continue with this condition for years and are referred to as so-called legacy patients, with residual lipodystrophy despite a switch to friendlier regimens, for reasons that are not clear,” Steven Grinspoon, MD, chief of the metabolism unit at Massachusetts General Hospital and an author of the study, told Contagion®. “The prevalence of NAFLD in HIV is high, and no one is expecting it to decrease soon, so there is a significant need for a therapeutic.”

Tesamorelin proved equally effective in men and women, working most efficiently in those who had the most fat to lose. While the hormone was developed specifically to help people with HIV who suffer from NAFLD, others may benefit, Grinspoon said: “[It] is not US Food and Drug Administration(FDA)-approved for use in non-HIV patients. Analogous studies are ongoing to determine if it reduces liver fat in non-HIV patients.”

Grinspoon said tesamorelin is not recommended in people with diabetes that is not under control, or in people with active cancers, although he added that negative effects such as increased glucose levels or higher malignancy rates have not been demonstrated. “This precaution is seen with all products that increase growth hormone, just to be safe,” he said.

In 2010, the FDA approved tesamorelin for use in people with HIV who suffer from lipodystrophy, and Grinspoon would like to see it prescribed more widely. “Certainly, it’s now even more compelling to use this drug in HIV patients with significant abdominal fat accumulation, many of who[m] are likely to have liver fat, which we now show to be reduced,” he said. “So, [there are] 2 benefits. We are working on larger studies to confirm our findings but the results are compelling and robust, and very exciting.”

Co-author Colleen Hadigan, MD, MPH, senior research physician at the National Institutes of Allergy and Infectious Diseases’ Laboratory of Immunoregulation, part of the NIH, agreed. “I think that this opens up an opportunity to rethink prescribing practices,” she told Contagion®, emphasizing that there’s no need for physicians to test for fatty liver in a patient who has HIV and abdominal fat before recommending tesamorelin. “This could be another piece of clinical information to justify adding another medication.”