Back HIV/AIDS HIV/AIDS Topics HIV-Related Conditions Metabolic Problems

AIDS 2014: Weight Gain on ART May Raise Risk of Heart Disease and Diabetes

People with HIV who gain weight shortly after starting antiretroviral therapy (ART) may have an increased risk of cardiovascular disease and diabetes, according to findings from the D:A:D study presented this week at the 20th International AIDS Conference in Melbourne, Australia.

alt

Read more:

CROI 2014: Tesamorelin Growth-Hormone Releaser Reduces Liver Fat in People with HIV

Tesamorelin, a synthetic form of growth-hormone-releasing hormone (GHRH), which the FDA has approved to reduce excess visceral abdominal fat in people living with HIV, also reduced associated liver fat in an HIV positive cohort chosen for abdominal adiposity, according to the results from a randomized, placebo-controlled trial presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) this week in Boston.

alt

Read more:

Elevated Triglyceride Level Increases Likelihood of Peripheral Neuropathy

HIV positive people with higher blood triglyceride levels are more likely to develop peripheral sensory neuropathy, or nerve damage, according to a study described in the January 14, 2011 issue of AIDS. Investigators suggested that the relationship might be due to changes in mitochondria function associated with elevated triglycerides.

Read more:

HIV Medicine Association Guidelines Emphasize Primary Care Needs of People with HIV on ART

The HIV Medicine Association (HIVMA) of the Infectious Disease Society of America (IDSA) this week released new Primary Care Guidelines for the Management of Persons Infected with Human Immunodeficiency Virus, focusing on primary care and prevention for HIV positive people on effective antiretroviral therapy (ART). The new guidelines, published in the November 13, 2013, online edition of Clinical Infectious Diseases (in print January 2014) "reflect the fact that people with HIV are now living normal life spans," according to an HIVMA/IDSA press release.

alt

Read more:

Tesamorelin Growth Hormone-releasing Factor Reduces Visceral Fat in Diverse Patient Groups

Tesamorelin (TH9507, brand name Egrifta), a recombinant form of human growth hormone-releasing factor, decreased the amount of visceral abdominal fat over 1 year in a variety of sub-populations of HIV patients with lipodystrophy, according to research presented at the recent 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). A related study found that fat loss measured by CT scans was reflected in reduced waist size and improved patient-reported body image.

Read more:

HIV11: Lipid Levels Are Higher among HIV+ People on ART, Immune Suppression May Play a Role

People with HIV on suppressive antiretroviral therapy (ART) have "considerably higher" blood lipid levels relative to untreated individuals or those on less effective treatment, researchers reported at the 11th International Congress on Drug Therapy in HIV Infection (HIV11) last month in Glasgow. They also found that greater immune deficiency, as indicated by lowest-ever CD4 count, was associated with lipid elevations.

alt

Read more:

Growth Hormone Releasing Factor Tesamorelin Reduces Visceral Fat in HIV Positive People with Lipodystrophy

The growth hormone releasing factor tesamorelin (brand name Egrifta, formerly TH9507)reduced the amount of visceral abdominal fat in HIV positive people with central fat accumulation and led to improved feelings about body image, researchers reported in the March 1, 2010 Journal of Acquired Immune Deficiency Syndromes. Tesamorelin lowered total cholesterol and did not cause significant side effects, including blood glucose abnormalities.

Abdominal fat accumulation -- an aspect of lipodystrophy syndrome -- is a concern for many HIV positive people, both in terms of body image and cardiovascular risk. Administration of human growth hormone has been shown to reduce visceral adipose tissue (fat deep within the abdomen), but it can lead to side effects including elevated blood glucose, swelling, bone pain, and carpal tunnel syndrome.

In contrast to administering growth hormone directly, tesamorelin is a growth hormone releasing factor that stimulates the pituitary gland in the brain to secrete more growth hormone. Investigators hypothesized that it might provide similar benefits with fewer adverse effects, and this was supported by initial studies.

Julian Falutz from McGill University School of Medicine and colleagues investigated the effects of tesamorelin in 404 HIV positive participants on antiretroviral therapy (ART) who had excess abdominal fat.

This double-blind Phase 3 trial consisted of 2 sequential parts. During the first 6 months, patients were randomly assigned (2:1) to receive daily subcutaneous injections of 2 mg tesamorelin or placebo. In the extension phase (months 6-12), participants initially receiving tesamorelin were randomly assigned (1:1) to either continue on the same tesamorelin regimen or switch to placebo, while patients initially randomized to placebo switched to tesamorelin.

The primary endpoint was changes in visceral adipose tissue, assessed with both CT and DEXA scans. Secondary endpoints included other body composition measurements, body image, levels of insulin-like growth factor-1 (a protein produced in response to growth hormone stimulation), and safety parameters.

Results

  • Visceral adipose tissue decreased by 10.9% (21 cm2 or about 1 kg) on average in the tesamorelin group versus a 0.6% (1 cm2 or about 0.2 kg) decrease in the placebo group during the first 6 months (P < 0.0001).
  • Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-to-hip ratio (P = 0.001) all improved significantly, with no changes in limb or subcutaneous abdominal fat.
  • Patients reported significantly less distress about belly appearance in the tesamorelin group compared with the placebo group (P = 0.02).
  • Physicians' ratings of patient belly appearance also improved significantly (P = 0.02).
  • Among participants who continued on tesamorelin for 12 months, visceral adipose tissue decreased by 17.5% (P < 0.001).
  • However, the visceral adipose tissue improvements of the first 6 months were rapidly lost in patients who switched from tesamorelin to placebo.
  • Patients receiving tesamorelin did not experience a significant decrease in triglycerides compared with placebo (as was seen in a prior Phase 3 study), but there was a trend in this direction.
  • Participants who received tesamorelin for 12 months experienced a significant decrease in total cholesterol.
  • Tesamorelin was well-tolerated overall.
  • Levels of insulin-like growth factor-1 increased significantly, but there was no apparent change in glucose parameters.
  • About 4% of participants experienced hypersensitivity reactions, which were generally mild; a few discontinued therapy prematurely for this reason.

Based on these findings, the study authors concluded, "Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose."

With these new data, they added, "there are now consistent results from two large Phase 3, randomized, placebo-controlled studies to suggest that [tesamorelin] is a potentially useful clinical strategy to selectively reduce visceral adipose tissue and improve body image among HIV-infected patients with abdominal fat accumulation in the context of antiretroviral therapy."

Montreal-based developer Theratechnologies has requested approval of tesamorelin from the U.S. Food and Drug Administration; and the agency will told a public meeting on May 27, 2010 to discuss the topic.

Affiliations: Department of Medicine, Montreal General Hospital and McGill University School of Medicine, Montreal, Canada; Massachusetts General Hospital and Harvard Medical School, Boston, MA.

4/2/10

Reference

J Falutz, D Potvin, JC Mamputu, and others. Effects of Tesamorelin, a Growth Hormone-Releasing Factor, in HIV-Infected Patients With Abdominal Fat Accumulation: A Randomized Placebo-Controlled Trial With a Safety Extension. Journal of Acquired Immune Deficiency Syndromes 53(3): 311-322. March 1, 2010.

Visceral Fat Reduction in HIV+ People on Tesamorelin Improves Metabolic Profile

The synthetic growth hormone-releasing factor tesamorelin (Egrifta) reduces internal abdominal fat in people with HIV, which in turn leads to improvements in lipid and glucose levels, researchers reported in the June 2012 issue of Clinical Infectious Diseases.alt

Read more:

Body Composition and Metabolic Changes in the SMART Treatment Interruption Trial

Intermittent antiretroviral therapy (ART) was associated with increased subcutaneous fat, but no changes in visceral abdominal fat, according to an analysis from the large SMART treatment interruption trial published in the January 2010 issue of AIDS. In addition, levels of both LDL (bad) and HDL (good) cholesterol decreased, while one measure of blood glucose increased.

Read more: