3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

A PILOT STUDY FOR THE USE OF PIOGLITAZONE IN THE TREATMENT OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY LIPODYSTROPHY SYNDROMES

Antiviral Therapy 2001; 6(Suppl. 4):32 (abstract no. 43)

A Calmy, B Hirschel, L Karsegaard, D Hans, B Mermillod, C Pichard and CA Meier
University Hospital Geneva, Switzerland

BACKGROUND: Pioglitazone is an anti-diabetic drug enhancing insulin sensitivity and promoting adipogenesis, thereby leading to a shift from central to peripheral fat deposition. Changes in fat distribution observed in HIV-positive patients contribute to dyslipidemia and insulin resistance. We hypothesized that pioglitazone might be beneficial in preventing and/or correcting some of these alterations.

OBJECTIVES: To evaluate in nine non-diabetic HIV-positive patients with lipodystrophy: (1) the safety of pioglitazone in combination with highly active antiretroviral therapy (HAART); (2) the effect of pioglitazone on body composition, lipid profile and insulin sensitivity.

METHODS: Open-label prospective trial with 30 and 45 mg/day of pioglitazone over 6 months with assessment of metabolic parameters and body composition (segmental dual-X-ray absorbsiometry, DEXA) at baseline and 6 months.

RESULTS: Results are expressed as mean ±1 SD. All patients treated with pioglitazone were on stable HAART, six of them on protease inhibitor (PI) therapy (5:1:3 years), and five of them also on stavudine (5:1:3 years). All patients experienced moderate to severe lipodystrophy at the beginning of the study (auto evaluation and doctors' evaluation). The adjunction of pioglitazone did not result in any serious side-effects and liver function tests remained unaltered (ΔALAT +10:1:29 U/l, P=0.13). Viral load (VL) was undetectable in nine and eight patients at baseline and at 6 months, respectively; Patients treated with pioglitazone experienced no significant changes in weight (+0.9:1:2.8 kg, P=0.1), waist/hip ratio (-0.033:1:0.03, P=0.95) or brachial perimeter (-0.38:1:1.4 cm, P=0.8). Lipid values were stable (Δ total cholesterol-0.12:1:1.2 mmol/l, P=0.2) with a tendency towards decreasing triglycerides (TG) levels (baseline TG 3.6:1:3.11 mmol/l, 6 months TG 2.5:1:0.9 mmol/l, P=0.4). The mean HbA₁c level at baseline was 4.8:1:0.5% and no patient had frank diabetes. At 6 months this value slightly to 5.4:1:0.15% (P=0.1). Insulin resistance index was normal at baseline and remained unchanged at 6 months. DEXA revealed no significant changes in total, arm and leg fat mass. However, using an auto evaluation questionnaire, four of the nine patients reported an improvement in their fat distribution.

CONCLUSIONS: In this pilot study the use of pioglitazone appears to be reasonably safe in HIV-infected patients on HAART. Within the 6 months of treatment with pioglitazone, we noted an improvement of the lipodystrophic changes in four of the nine patients and a stabilization of metabolic alterations. Since pioglitazone is safe and may be efficacious in preventing the progression of metabolic alterations on HAART, a randomized and controlled trial will be required to validate these findings.

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