|
Treatment
with Recombinant Human Growth Hormone (r-hGH) Decreases Visceral
Adipose Tissue in HIV Patients with Fat Redistribution Syndrome
Daily
use of Serono Laboratories’ recombinant human growth hormone (rhGH)
[somatropin--rDNA origin for injection; Serostim] decreases
visceral adipose tissue in patients with HIV-associated adipose
redistribution syndrome (HARS), according to data published in the
March 1, 2004 edition of the Journal of AIDS.
Some
people with HIV/AIDS develop fat maldistribution with visceral adipose
tissue (VAT) accumulation and metabolic abnormalities. In general,
HARS patients accumulate excess visceral adipose tissue in the abdomen
or may develop a fat pad on the upper back commonly known as a “buffalo
hump.”
There is currently no FDA-approved medical
treatment for HARS. “While further study is needed, Serostim®
has promise as a potential treatment for visceral fat accumulation
in patients with HARS,” said Donald P. Kotler, M.D., St. Luke’s
Roosevelt Hospital, New York, and a lead investigator in the study.
The
Serostim® in the Treatment of Adipose Redistribution
Syndrome (STARS) trial was a multi-center, randomized, double-blind,
placebo-controlled study that included 245 patients at trial sites
located throughout the US. The study was designed to evaluate the
efficacy and safety of two different dosing schedules of recombinant human growth hormone therapy.
Patients with excess VAT received placebo (PL), recombinant
human growth hormone at a dose of 4 mg daily (DD) or 4 mg on alternate
days (AD) for 12 weeks.
For weeks 12 to 24, DD patients were re-randomized to PL (DD-PL)
or AD (DD-AD), AD patients continued on AD (AD-AD), and PL patients
were switched to DD (PL-DD).
Results
From baseline to week 12, VAT decreased significantly compared
with PL in DD (-8.6%, P < 0.001) but not in AD (-4.2%,
P = 0.052). Trunk-to-limb fat ratio decreased significantly
in both (P < 0.001) compared with PL, as did total cholesterol
and non-high-density lipoprotein (HDL) cholesterol (-4.5% and -7.5%
in DD, -4.3% and -6.2% in AD).
At week 24, all groups displayed significant (P <
0.05) reductions in VAT (-5.3% to -9.5%) and trunk fat (-7.8% to
-22.8%). DD-AD and AD-AD also displayed significant (P
< 0.05) reductions in non-HDL cholesterol.
Adverse reactions reported during this clinical trial were
consistent with those expected within the current approved indication
for rhGH. The most common adverse events associated with rhGH therapy are mild to
moderate muscle and joint pain and swelling, which occur in a dose-related
manner and often subside with continued treatment or dose reduction.
Conclusions
These
results suggest that rhGH dosed at 4 mg daily for 12 weeks decreases
VAT and cholesterol concentrations in HIV-infected patients with
excess VAT. The optimal regimen to sustain these effects awaits
determination.
Discussion
Fat
maldistribution can be disfiguring, debilitating, and stigmatizing
and may lead to nonadherence to antiretroviral therapy. Another
concern is that fat maldistribution, particularly visceral adipose
tissue (VAT) accumulation and associated abnormalities, may promote
premature atherogenesis.
Current
data indicate that excess VAT is not substantially reversed by discontinuation
or switching of antiretroviral therapy. Diet and exercise interventions
may reduce adiposity and metabolic risk factors in HIV patients
as they do in some obese patients without HIV, but responses may
not be sustained.
No
medical therapies are presently approved by the US Food and Drug
Administration (FDA) to reduce excess VAT in patients with HIV-1
infection.
It
is well known that rhGH reduces VAT and improves lipid levels in
HIV-negative patients with growth hormone (GH) deficiency. The observed reductions in VAT and trunk fat in this study confirm findings
in preliminary open-label trials in HIV patients treated with rhGH
for abnormal fat accumulation and in patients with excess VAT but
without HIV infection.
As observed previously by others, GH reduces central fat to
a much greater degree than it does peripheral fat. The patients
in this study with the greatest exposure to GH at week 24 (the DD-AD
group) lost only 0.7 kg of fat from the limbs as compared with 2.3
kg of fat from the trunk. The fat loss on rhGH occurred without
loss of weight, because the patients in this study, as in other
studies of GH, gained lean body mass.
The
observed reductions in VAT and trunk fat in this study were accompanied
by improvements in serum lipid levels (discussed further below),
body image, distress about the size and shape of the body, and QOL.
These improvements significantly correlated with reduction of central
fat. It is likely, although unproven, that the modest changes in
VAT and trunk fat in this study were also of a magnitude large enough
to reduce risk of CVD.
Specific
data that relate the level of cardiovascular risk to the level of
excess VAT or the amount of VAT reduction to amount of risk reduction
have not yet been published. Nevertheless, it is known that even
modest losses of weight can improve lipid parameters and produce
other benefits in obese HIV-uninfected people, including reducing
the risk of developing CVD. Cardiovascular risk factors are more
closely related to VAT than to weight.
Consequently,
VAT loss may mediate the effects of weight loss on lipids and other
factors and lower CVD risk more than does weight loss. In addition,
excess VAT and central fat are related to indicators of CVD independently
of lipid levels. Therefore, rhGH may lower CVD risk in several ways
at once.
Lipid-lowering therapy in HIV-infected patients on protease
inhibitors frequently fails to restore lipid values to normal, and
some lipid-lowering agents widely used in the general population
are contraindicated in HIV-infected patients because of drug-drug
interactions.
HIV-infected patients with HARS, who have both increased VAT
and decreased SAT, are especially hard to treat to goal. GH may
offer an additional therapeutic option because it simultaneously
lowered non-HDL cholesterol and raised HDL cholesterol in HIV patients
who were not on lipid-lowering agents and reduced total cholesterol
in HIV patients who were taking lipid-lowering agents as well as
in those who were not.
The
optimal therapy for excess VAT in HIV infection has yet to be determined.
The results of the present study suggest that rhGH at a dose of
4 mg daily for 12 weeks is both reasonably effective and safe for
patients presenting with HARS who do not have elevated fasting glucose,
impaired glucose tolerance, or diabetes.
03/03/04
Reference
D P Kotler and others. Effects of Growth Hormone on Abnormal
Visceral Adipose Tissue Accumulation and Dyslipidemia in HIV-Infected
Patients. Journal
of Acquired Immune Deficiency Syndromes 35(3): 239-252. March 1, 2004.
|
