Correspondence

Effects of Growth Hormone–Releasing Factor in HIV-Infected Patients

N Engl J Med 2008; 358:969-970February 28, 2008

Article

To the Editor:

In their article on the effects of growth hormone−releasing factor in patients with human immunodeficiency virus (HIV) infection, Falutz and colleagues (Dec. 6 issue)1 state that tesamorelin, a synthetic growth hormone–releasing factor, might be useful in the treatment of lipodystrophy related to antiretroviral drugs. However, the primary end point of the trial was the reduction of visceral adipose tissue as assessed by computed tomographic scanning; the study was not designed to detect a reduction in cardiovascular risk. These results came after the decision by the Food and Drug Administration (FDA) not to grant as an indication for growth hormone treatment the HIV-associated adipose redistribution syndrome (HARS).2

The recent torcetrapib case demonstrated that despite the increase in high-density lipoprotein cholesterol, cardiovascular events were increased in torcetrapib-treated patients.3 Medical hypotheses have to be demonstrated by data. The effect of tesamorelin should be assessed in a clinical trial with a primary end point of a reduction in cardiovascular events.

Renato Bertini Malgarini, M.D.
Giuseppe Pimpinella, Ph.D.
Agenzia Italiana del Farmaco, 00144 Rome, Italy
r.bertini@aifa.gov.it

3 References

1. 1

   Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med 2007;357:2359-2370
   Full Text | Web of Science | Medline

2. 2

   Detailed view: safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER) — July 2007. (Accessed February 7, 2008, at http://www.fda.gov/medwatch/safety/2007/jul07.htm#Serostim.)
   

3. 3

   Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-2122
   Full Text | Web of Science | Medline

Author/Editor Response

Our study was designed in consultation with the FDA to test the effects of a growth hormone–releasing factor analogue on cardiovascular-risk factors in HIV-infected patients. Both visceral fat and dyslipidemia improved in response to tesamorelin. In contrast to growth hormone,1 negative effects on glucose were not seen. With tesamorelin, unlike torcetrapib,2 there are no data to date showing negative effects on cardiovascular risk factors; therefore, there is no suggestion of a potential risk of increased event rates. Moreover, patients feel less distress in association with the reduction in visceral adiposity and thus may be more likely to continue antiretroviral therapy. As strategies are designed to reduce cardiovascular risk in HIV-infected patients, it will be critical to monitor them for any potential negative effects, as suggested by Malgarini and Pimpinella. Studies to determine effects on cardiovascular events may be difficult to perform and take years to complete. In the interim, patients might nonetheless benefit from strategies that have positive effects on quality of life and known cardiovascular risk factors, that are without toxicity, and that help to maintain successful treatment with antiretroviral therapy.

Julian Falutz, M.D.
McGill University Health Centre, Montreal, QC H3G 1A4, Canada

Steven Grinspoon, M.D.
Harvard Medical School, Boston, MA 02115
sgrinspoon@partners.org

2 References

1. 1

   Grunfeld C, Thompson M, Brown SJ, et al. Recombinant human growth hormone to treat HIV-associated adipose tissue redistribution syndrome: 12-week induction and 24-week maintenance therapy. J Acquir Immune Defic Syndr (in press).
   

2. 2

   Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357:2109-2122
   Full Text | Web of Science | Medline