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Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized Double-Blind Placebo-Controlled Trial (ANRS 113) with 130 patients
L Slama1, E Lanoy2, M A Valentin2,3, J P Bastard1,4, A Chermak2, A Boutekatjirt3, D William-Faltaos3, J Capeau1,4, D Costagliola2, and Willy Rozenbaum*1,5
1Hosp Tenon, Paris, France; 2INSERM U720, Hosp Pitie-Salpetriere, Paris, France; 3Hosp Pitié-Salpétrière, Paris, France; 4INSERM U680, Paris, France; and 5Hosp Saint Louis, Paris, France
Background: HIV lipodystrophy is
a frequent treatment side-effect in HIV-1 infected patients. Thiazolidinediones, PPARg agonists, have been shown to
increase subcutaneous fat in non-HIV infected patients. However, rosiglitazone has shown disappointing results on
HIV-related lipoatrophy and worsened lipid profile. Pioglitazone (PIO), which has different effects on lipid
profile, deserved further investigation.
Methods: HIV-1+ adults with self-reported lipoatrophy
confirmed by physical examination, with a plasma HIV-1 RNA <400 copies/mL, CD4 cells >200/mm3 and with unchanged ART
for the past 6 months, were randomized to PIO 30 mg once daily or placebo for
48 weeks. The primary efficacy endpoint was the change in limb fat between
weeks 0 and 48 as evaluated by DEXA. The study had a
80% power to detect a 0.325-kg change in limb fat between groups at week 48 by
intent-to-treat analysis, with a type-I error of 5% and a 2-sided non
parametric test.
Results: Baseline characteristics were well balanced
between PIO (n = 64) and placebo (n = 66) groups for clinical and
biological data, signs of lipoatrophy, body
composition, duration, and composition of previous or current therapy including
stavudine (d4T). Limb fat increased by 0.38 kg in the
PIO and 0.05 kg in the placebo group at week 48 (mean difference, 0.33 (95%CI
0.10 to 0.56 kg; p = 0.051). In
patients not receiving d4T, an increase of 0.45 vs
0.04 kg was observed (mean difference, 0.40; 95%CI 0.12 to 0.69 kg; p = 0.013), but not in patients on d4T (p = 0.404). Overall, there was no
significant difference in subcutaneous abdominal fat or in visceral fat areas
on computed tomography at L4 vertebra. Improvement in thigh circumference (+1.4
cm vs 0.2; p
= 0.017) and tricipital skin-fold thickness (+0.9 mm vs 0.4; p = 0.047)
were also observed in the PIO group. However, the patients perceived no
improvement. The lipid profile was not significantly different between the 2
groups at week 48 except for HDL cholesterol which was improved in the PIO
group (+0.08 mmol/L vs –0.08;
p = 0.005). There were 16 serious
adverse events, 10 in the PIO group and 6 in the placebo group.
Conclusions: PIO 30 mg once daily for 48 weeks improved limb lipoatrophy
in antiretroviral-treated HIV-1-infected patients. This effect was not seen in
patients exposed to d4T. PIO did not alter lipid parameters except for HDL
cholesterol that was increased by PIO. These results support the use of PIO for
the treatment of HIV-related lipoatrophy.
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