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Treatment
with Pioglitazone But Not with Fenofibrate Improves HAART-related
Metabolic Syndrome
Results
of a randomized, placebo-controlled, double blind trial show that
administration of pioglitazone,
but not fenofibrate, improved insulin
resistance, blood pressure, and lipid profile over a 12-month period in patients
with HAART-induced
metabolic syndrome. The study results appear in the March
1, 2005 issue of Clinical Infectious Diseases.
Background
HAART
leads to profound and sustained suppression of HIV-1
replication, but it also results in the development
of a metabolic syndrome, which confers an increased
risk for developing premature atherosclerotic cardiovascular
disease.
Pioglitazone,
1 of the 2 thiazolidinediones that are currently
available, improves insulin resistance and has a
more favorable effect on lipid profile than does
rosiglitazone in non HIV-infected patients with diabetes.
Although
a few studies on the role of rosiglitazone
in HAART-induced metabolic syndrome have been published , no randomized, placebo-controlled studies of
the use of pioglitazone have been published.
In addition, although open-label, uncontrolled studies
have reported that fenofibrate, a fibric acid
derivative, improves dyslipidemia and hyperglycemia in patients with HAART-induced metabolic syndrome
, no randomized trials have been published to
date.
Trial Design
Researchers at Beth Israel Deaconess Medical Center, and Joslin Diabetes Center, Boston, Massachusetts designed
a 2 × 2 factorial, randomized, double-blinded,
placebo-controlled study to evaluate the effect of pioglitazone and fenofibrate administration
for 1 year in patients who developed metabolic
abnormalities after starting HAART.
14 subjects were randomized to receive treatment,
7 subjects received active pioglitazone and
7 received the corresponding placebo, whereas 6 subjects received active fenofibrate and 8 received
the corresponding placebo. The study group
included 13 men and 1 woman, with a mean age (±SD) of 48 ± 8.6 years.
Five
subjects had mixed-fat
redistribution, 5 subjects had fat accumulation, 3 subjects
had fat wasting,
and 1 subject did not have any fat redistribution; there was no
significant difference in the number of subjects with the different
types of fat redistribution among the treatment groups.
Six subjects received a diagnosis of diabetes,
1 had impaired fasting glucose levels, and
7 had insulin resistance at baseline; there was
no significant difference in the distribution of subjects with these characteristics among the treatment
groups.
Results
In
contrast to the previous open-label study to evaluate pioglitazone
therapy among 11 HIV-positive patients receiving HAART, the investigators
found that, consistent with the effects seen in non-HIV-infected
subjects with diabetes, pioglitazone improves insulin resistance
and favorably affects the lipid profile by decreasing triglyceride
levels and increasing HDL
cholesterol levels.
In
addition, although LDL cholesterol levels tended
to increase, the LDL particle size tended to
increase, too, which resulted in lower levels of
atherogenic LDL cholesterol. In contrast, rosiglitazone
increased cholesterol and triglyceride levels.
However,
conflicting, yet limited, data exist on the effect
of these 2 medications on the body composition
of patients who are receiving antiretroviral therapy.
We also report, for the first time, that,
in agreement with data from rodent studies, pioglitazone
treatment improved blood pressure in subjects with
HAART-induced metabolic syndrome.
Conclusions
In
conclusion, pioglitazone is efficacious and well tolerated in the treatment of HAART-induced metabolic syndrome.
Because pioglitazone has effects similar to
those of rosiglitazone on insulin resistance and glucose metabolism, comparative studies of rosiglitazone
are warranted to demonstrate whether pioglitazone has more beneficial effects on the lipid profile and hypertension.
This
would justify the preferential use of pioglitazone for HIV-positive
subjects who develop HAART-induced metabolic syndrome. Additional,
larger studies to investigate the effect of fenofibrate in patients
with higher triglyceride levels-possibly for each lipodystrophy
subgroup separately are also
warranted, as are larger studies to investigate the role of treatment
with pioglitazone in combination with fenofibrate.
02/14/05
Reference
A Gavrila and others. Improvement in Highly Active Antiretroviral TherapyInduced Metabolic Syndrome by Treatment with Pioglitazone but Not with Fenofibrate: A 2 × 2
Factorial, Randomized, Double-Blinded, Placebo-Controlled Trial.
Clinical Infectious Diseases 40(5):
745-749. March 1, 2005.
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