HIV and Hepatitis.com Coverage of the 15th
Conference on Retroviruses and Opportunistic Infections (CROI 2008) February
3 - 6, 2008, Boston, MA
The
material posted on HIV and Hepatitis.com about CROI 2008 is not approved by
nor is it a part of CROI 2008.
Growth
Hormone and GH Releasing Factor (Tesamorelin) for HIV-related Lipodystrophy
Recombinant
human growth hormone (GH), a manufactured version of a natural hormone produced
by the pituitary gland in the brain, is approved for the treatment of HIV-related
wasting syndrome and has also been studied as a therapy for lipodystrophy. GH
plays a key role in metabolism and regulation of body composition; some prior
research indicates that HIV patients with lipodystrophy tend to have low GH levels.
Growth
hormone releasing factor (GHRF) - a hormone produced by the hypothalamus that
in turn stimulates the pituitary to secrete more GH - has also been studied for
lipodystrophy, in the hopes that it would provide similar benefits without the
side effects of direct GH administration, which may include elevated blood glucose,
swelling, bone pain, and carpal tunnel syndrome.
Steven
Grinspoon, MD, and colleagues from Massachusetts General Hospital presented the
latest data from a long-term prospective trial of GH in 56 HIV patients with lipodystrophy.
At baseline, participants had reduced GH secretion. They were randomly assigned
to receive subcutaneous injections of placebo or low doses of replacement GH to
bring them to the upper quartile of the normal physiological range (average dose
4.1 mcg/kg/day).
The
investigators controlled for several potentially confounding factors including
patient age, sex, testosterone use, duration of antiretroviral therapy, blood
pressure, smoking, and use of anti-hypertensive and lipid-lowering medications.
Results
•
Patients in the GH group experienced a significantly larger decrease in visceral
adipose tissue compared with the placebo arm (-22 vs -4 cm2).
•
Decreases in trunk-to-extremity fat ratio (-0.4 vs -0.007) and trunk fat (-0.5
vs +0.2) were also greater in the GH arm.
•
Levels of insulin-like growth factor-1 (IGF-1) increased significantly more in
the GH group compared with the placebo arm (+109 vs -25 ng/mL).
•
Diastolic blood pressure and triglyceride levels improved more in the GH group,
but carotid artery intima-media thickness (an indicator of atherosclerosis) did
not change with GH vs placebo.
•
The blood glucose level 2 hours after an oral glucose challenge test increased
in the GH arm relative to placebo (+16 vs -4 mg/dL).
•
However, the overall frequency of adverse events associated with GH was similar
in the GH and placebo arms (22% vs 28%).
•
HIV viral load and CD4 were unchanged in both arms.
"Physiologic
GH replacement significantly reduced visceral fat and truncal obesity, triglycerides,
and diastolic blood pressure, and was well-tolerated," the researchers concluded.
They added, however, that "GH increased 2-hour glucose and had no
effect on carotid IMT in patients with HIV lipodystrophy and relative GH deficiency
over a long period of 18 months."
GH Releasing
Factor (Tesamorelin)
Another research team (which also included
Grinspoon) presented data from a 52-week safety and efficacy study of tesamorelin
(TH9507), a GHRF analog, in HIV patients with abdominal fat accumulation - a concern
since, it visceral abdominal fat is associated with an elevated risk of cardiovascular
disease.
The study included 410 HIV-infected participants on antiretroviral
therapy who were randomly assigned to receive 2 mg daily subcutaneous tesamorelin
or placebo for 26 weeks. After 26 weeks, subjects taking tesamorelin were again
randomized to either switch to placebo or continue on tesamorelin through 52 weeks,
while initial placebo subjects switched to tesamorelin.
Previously
reported data showed that tesamorelin led to significant improvements in visceral
adipose tissue (VAT), blood lipid levels, and patient-reported outcomes at week
26, as well as sustained VAT loss in those who continued on tesamorelin through
week 52.
At CROI, the investigators reported longer-term safety and body
composition data. The study population for this analysis included 275 men and
40 women, with a mean age of 48 years.
Results
•
There were no clinical differences in shifts from normal to high fasting glucose
levels between patients treated with tesamorelin for 52 weeks (12%) vs 26 weeks
(11%), compared with 10% in the placebo arm.
•
The percentage of patients who went from normal to abnormal 2-hour oral glucose
tolerance test results was about 12% in both the 26-week and 52-week tesamorelin
groups.
•
At 52 weeks, patients on tesamorelin had a clinically significant decrease in
triglycerides, while maintaining cholesterol levels within the normal range.
•
52-week decreases from baseline in VAT were 17% in men and 23% in women who continued
on tesamorelin.
•
The decrease from baseline in trunk fat at week 26 was sustained at week 52 with
continued tesamorelin treatment, but there were no further changes in subcutaneous
abdominal fat (SAT) or limb fat.
•
The increase from baseline in lean body mass at week 26 was sustained at week
52 among patients who continued on tesamorelin.
"Treatment
with 2 mg tesamorelin for 52 weeks was overall well tolerated, without clinical
effect on glucose parameters, and resulted in improved body composition, including
maintenance of VAT loss and preservation of subcutaneous adipose tissue and limb
fat," the investigators concluded. "These results suggest that tesamorelin
may be beneficial for the treatment of HIV patients with lipohypertrophy."
Fat
decreases were reversed, however, in patients who stopped tesamorelin after the
first 26 weeks, suggesting that continued treatment is necessary for sustained
improvement.
3/14/08
Sources
J
Lo, S You, B Canavan, and others. Effects of 18-Month Physiological GH Replacement
in Relatively GH-deficient Patients with HIV Lipodystrophy. 15th Conference on
Retroviruses and Opportunistic Infections (CROI 2008). Boston, MA. February 3-6,
2008. Abstract 146LB.
Growth
Hormone and GH Releasing Factor (Tesamorelin) for HIV-related Lipodystrophy 
Results
