New drug reduces abdominal fat accumulation and improves lipids in HIV-infected patients

December 05, 2007

Treatment with an investigational drug that induces the release of growth hormone significantly improved the symptoms of HIV lipodystrophy, a condition involving the redistribution of fat and other metabolic changes in patients receiving combination drug therapy for HIV infection. A team led by researchers from Massachusetts General Hospital (MGH) and McGill University Health Centre found that treatment with tesamorelin, a growth-hormone-releasing factor, significantly reduced deep abdominal fat deposits and improved the metabolic aspects of HIV lipodystrophy in a group of patients with the syndrome. The report of a six-month Phase 3 clinical trial of tesamorelin appears in the December 6 New England Journal of Medicine.

"This appears to be the most promising strategy to date for a safe, effective method of reducing excess visceral fat deposits and improving lipid abnormalities in HIV-infected patients, thereby improving their risk for cardiovascular disease," says Steven Grinspoon, MD, of the MGH Neuroendocrine Unit and Program in Nutritional Metabolism, the report's senior and corresponding author.

A significant number of HIV-infected individuals who receive antiviral therapy develop lipodystrophy. Symptoms of the syndrome include a loss of subcutaneous fat in the face, arms, and legs and increased fat deposits in the abdomen. The metabolic aspects of the syndrome - changes in cholesterol and other blood lipids, and development of insulin resistance - could increase the risk of cardiovascular disease in HIV-infected patients.

Earlier studies found that growth hormone secretion is reduced in men with lipodystrophy. Since directly injecting growth hormone can have significant side effects, researchers at the MGH previously investigated the use of growth-hormone-releasing hormone (GHRH) to increase levels in a way that mimics natural control of hormone levels. In a 2004 study, they showed that patients receiving GHRH injections appeared to have more normal growth hormone levels and improvements in fat distribution.

The current study followed up an earlier Phase 2 study of tesamorelin, a growth-hormone-releasing factor that can be dosed only once a day instead of twice. Study participants - HIV lipodystrophy patients recruited from 43 sites around the U.S. and Canada - were randomly assigned to receive either tesamorelin or a placebo, self administered daily for six months. At the end of the study period, researchers measured participants' visceral fat - deposits around organs deep in the abdomen - and subcutaneous fat in arms and legs. They also recorded key lipid measurements and levels of the hormone IGF-1, which reflects the release of growth hormone. In addition, participants were surveyed at the beginning and end of the study on their perceptions of their bodies and any distress they felt.

Among the more than 325 participants who completed the study, those receiving tesamorelin had significant reductions in abdominal fat, measured by CT scan, resulting in a 20 percent difference from those in the placebo group. Lipid measurements - including triglycerides, total cholesterol, HDL, and the ratio of total cholesterol to HDL - also improved significantly; IGF-1 levels reflected increased release of growth hormone in the tesamorelin group. Participants receiving the drug also reported significant improvements in their body image and reduced levels of distress.

"Longer-term studies are necessary to confirm our results, and another confirmatory Phase 3 trial needs to be completed to comply with FDA requirements," says Grinspoon. "But this study shows clearly that the novel strategy of inducing the release of endogenous growth hormone can improve symptoms of lipodystrophy, relieving patient distress - which may improve their compliance with therapy - and reducing several cardiovascular risk factors." Grinspoon is an associate professor of Medicine at Harvard Medical School.
The study was supported by Theratechnologies, a biopharmaceutical company based in Montréal that is developing tesamorelin, and the data were analyzed by Quintiles, Canada. Julian Falutz, MD, of McGill University Health Center, is the first author. Additional co-authors are Soraya Allas, MD, PhD, Koenraad Blot, MD, and Diane Potvin, MSc, Theratechnologies; Donald Kotler, MD, Columbia College of Physicians and Surgeons; Michael Somero, MD, Palm Springs, Calif.; Daniel Berger, MD, Northstar Health Care, Chicago; Stephen Brown, MD, AIDS Research Alliance, Los Angeles; Gary Richmond, MD, Ft. Lauderdale, Fla.; Jeffrey Fessel, Kaiser Foundation Research Institute, San Francisco; and Ralph Turner, MD, PhD, Phase V Techologies, Wellesley, Mass.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Massachusetts General Hospital

Related HIV Articles from Brightsurf:

BEAT-HIV Delaney collaboratory issues recommendations measuring persistent HIV reservoirs
Spearheaded by Wistar scientists, top worldwide HIV researchers from the BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy (BEAT-HIV Collaboratory) compiled the first comprehensive set of recommendations on how to best measure the size of persistent HIV reservoirs during cure-directed clinical studies.

The Lancet HIV: Study suggests a second patient has been cured of HIV
A study of the second HIV patient to undergo successful stem cell transplantation from donors with a HIV-resistant gene, finds that there was no active viral infection in the patient's blood 30 months after they stopped anti-retroviral therapy, according to a case report published in The Lancet HIV journal and presented at CROI (Conference on Retroviruses and Opportunistic Infections).

Children with HIV score below HIV-negative peers in cognitive, motor function tests
Children who acquired HIV in utero or during birth or breastfeeding did not perform as well as their peers who do not have HIV on tests measuring cognitive ability, motor function and attention, according to a report published online today in Clinical Infectious Diseases.

Efforts to end the HIV epidemic must not ignore people already living with HIV
Efforts to prevent new HIV transmissions in the US must be accompanied by addressing HIV-associated comorbidities to improve the health of people already living with HIV, NIH experts assert in the third of a series of JAMA commentaries.

The Lancet HIV: Severe anti-LGBT legislations associated with lower testing and awareness of HIV in African countries
This first systematic review to investigate HIV testing, treatment and viral suppression in men who have sex with men in Africa finds that among the most recent studies (conducted after 2011) only half of men have been tested for HIV in the past 12 months.

The Lancet HIV: Tenfold increase in number of adolescents on HIV treatment in South Africa since 2010, but many still untreated
A new study of more than 700,000 one to 19-year olds being treated for HIV infection suggests a ten-fold increase in the number of adolescents aged 15 to 19 receiving HIV treatment in South Africa, according to results published in The Lancet HIV journal.

Starting HIV treatment in ERs may be key to ending HIV spread worldwide
In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease.

NIH HIV experts prioritize research to achieve sustained ART-free HIV remission
Achieving sustained remission of HIV without life-long antiretroviral therapy (ART) is a top HIV research priority, according to a new commentary in JAMA by experts at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Lancet HIV: PrEP implementation is associated with a rapid decline in new HIV infections
Study from Australia is the first to evaluate a population-level roll-out of pre-exposure prophylaxis (PrEP) in men who have sex with men.

Researchers date 'hibernating' HIV strains, advancing BC's leadership in HIV cure research
Researchers have developed a novel way for dating 'hibernating' HIV strains, in an advancement for HIV cure research.

Read More: HIV News and HIV Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to