Pioglitazone subjectively improves body shape abnormalities

Lipodystrophy is a multifactorial syndrome that occurs in HIV-infected patients. It is clear that many factors play a role in the development of this condition, including disease and host-related factors and the use of highly active antiretroviral therapy (HAART).

Unfortunately, treatment options remain limited and some studies have been discouraging regarding potential treatments to correct or mitigate this dread condition.

Some preliminary data have indicated that anti-diabetic drugs, including the glitazones, may have some impact on the fat distribution in non-HIV lipodystrophy. The glitazones have been theorised to be able to prevent the toxic effect of protease inhibitors on adipogenesis in vitro by enhancing perixosome proliferator-activated receptor activity.

In a study published in AIDS, investigators at the HIV clinic of University Hospital Geneva assessed the safety and preliminary efficacy of treatment with pioglitazone for six months in 11 patients with lipodystrophy who were receiving highly active antiretroviral therapy (HAART).

The enrolled patients’ ages ranged from 30 to 51 years, all had undetectable viral loads, and the mean CD4 cell count and duration of HAART was 683 cells/mm3 and 3.8 years, respectively. In the study, pioglitazone was given at a dose of 30mg per day for three months and then 45mg a day for an additional three months.

A dual-energy X-ray (DEXA) absorbtiometry scan was performed at baseline and at month six to assess body composition. In addition, standard analyses were performed to quantify the fat content in various body regions of interest and lipids and insulin levels were measured.

The investigators found that body fat mass (total and leg) increased significantly, but there were no changes regarding the lipid profile. In the study, all but one patient had an increase in total fat mass as measured by DEXA scan after six months of pioglitazone treatment, with a median increase from 15.4% to 18.5% (P = 0.05). In addition, patient satisfaction was evaluated by questionnaire and a comparison of photographs showed that six out of 11 patients detected small improvements in a lipoatrophic area, one patient experienced a significant improvement in his physical appearance, two patients showed a continued progression of their lipodystrophy, and two patients did not notice any changes. No serious side effects were observed.

The authors conclude: “We found that pioglitazone treatment for a period of at least six months in non-diabetic HIV-positive patients on HAART was well tolerated and was associated with an increase in total body fat as well as a subjective improvement in body shape in seven out of 11 patients.”

The authors urge that further, larger studies be conducted to evaluate this potential treatment for lipodystrophy.

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Comment

This was an small, uncontrolled study and only produced a very modest effect (median 3% total fat increase after six months treatment). These results are difficult to interpret and are in contrast to findings from a better designed study with rosiglitazone. Data from non-HIV lipodystrophy were generated with troglitazone another member of this family which was taken off the market due to hepatotoxity.

It is interesting that no changes were found in lipid profile, as pioglitazone has favourable effects on lipids in type 2 diabetes, in contrast to rosiglitazone.