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Glitazones in lipodystrophy syndrome induced by highly active antiretroviral therapy: in small pilot study
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Anti-diabetic glitazones are known to alter fat distribution in non-HIV
lipodystrophy. We therefore assessed the safety and preliminary efficacy of
treatment with pioglitazone for 6 months in 11 patients with lipodystrophy
related to highly active antiretroviral therapy (HAART). No serious
side-effects were observed. Body fat mass (total and leg) increased
significantly, whereas no changes were found in the lipid profile. The good
tolerance and fat redistribution observed with pioglitazone warrants a larger
randomized trial in patients with HAART-related lipodystrophy.
Lipodystrophy syndrome is a major problem for the long-term use of highly
active antiretroviral therapy (HAART) in HIV-positive patients. No single
treatment has been validated to date, and the management of this disorder is
essentially empiric. As glitazones are thought to prevent the toxic effect of
protease inhibitors on adipogenesis in vitro by enhancing perixosome
proliferator-activated receptor [gamma] activity, we postulated that this
class of drug might be useful in the treatment of lipodystrophy in
HIV-1-infected patients on HAART.
Eligible patients were HIV-positive individuals attending the HIV clinic of
University Hospital Geneva with clinical lipodystrophy (including
lipoatrophy), as assessed by doctors and by the patients themselves
(questionnaire). The patients' ages ranged from 30 to 51 years, the mean CD4
cell count was 683 cells/mm3 (range 425-1415) and the viral load was
undetectable in all patients at baseline. The mean duration of the
antiretroviral regimen was 3.8 years. The study was designed as an open label
prospective trial in which each patient was compared with his or her own
baseline status.
Pioglitazone was given at a dose of 30 mg per day for 3 months and then 45 mg
a day for a further 3 months. A dual-energy X-ray (DEXA) absorbtiometry scan
was performed at months 0 and 6 using the Prodigy machine to assess body
composition. Standard and customized regional analyses were performed to
quantify the fat content (expressed as a percentage) in the region of
interest likely to be affected by lipodystrophic changes: mid-leg, mid-arm,
truncal and whole body. Plasma concentrations of cholesterol (total and
HDL-cholesterol) and triglycerides were determined using a direct enzymatic
method.
We monitored liver function tests on a monthly basis, but no significant
increase was observed. All but one patient remained virologically suppressed.
No statistically significant changes in anthropometric measures (body mass
index and waist-to-hip ratio) were found, and we noticed no significant
changes in total cholesterol, triglyceride and in LDL-cholesterol values at
baseline and after 6 months. None of our patients had diabetes or glucose
intolerance at baseline; nevertheless, the insulin levels and the aIRI were
significantly higher at 6 months. We observed at baseline a leptin deficiency
in seven out of eight men and one out of three women, which did not
significantly change at the end of the study. We found a strong correlation
between baseline total fat mass and leptin level (correlation coefficient r =
0.7, P = 0.06), but the changes in body mass between months 0 and 6 were not
correlated with the changes in the leptin level (correlation coefficient r =
0.19, P = 0.56).
All but one patient showed an increase in total fat mass as measured by DEXA
scan after 6 months of pioglitazone treatment; indeed, the total fat content
increased from a median of 15.4% (11.3-17.8) to 18.5% (12.4-20.3), which
difference was significant (P = 0.05). The authors reported improvements in body fat content as measured by DEXA
from baseline to month 6: truncal 15.4% to 18.5%; left arm 9.7% to 12.1%;
right leg 7.3% to 9.6%
Patient satisfaction was evaluated by questionnaire and a comparison of
photographs: six out of 11 patients detected small but encouraging changes in
lipoatrophic area, one experienced a significant amelioration of his physical
appearance, two patients showed a continuous progression of their
lipodystrophy, and two patients did not notice any changes.
AIDS 2003; 17(5):770-772. Alexandra Calmy et al. Divisions of Infectious
Diseases, Hopital Cantonal Universitaire, Geneva, Switzerland.
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