Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized, Double Blind, Placebo-Controlled Trial in 130 Patients

Effect of Pioglitazone on HIV-1 Related Lipoatrophy: a Randomized, Double Blind, Placebo-Controlled Trial in 130 Patients

A Randomized, Phase 3, Double Blind, Multicentre Trial, Evaluating the Effect of Pioglitazone Versus Placebo on Change in Lipoatrophy in HIV- 1 Infected Patients Treated With Stable Antiretroviral Therapy for at Least 6 Months.ANRS 113 LIPIOT Study

The aim of this randomized study is to compare the effect of pioglitazone versus placebo on change in limb fat in HIV 1-infected patients treated with antiretroviral therapy for at least 6 months and with clinical lipoatrophy.

Lipodystrophy is one of the most frequent treatment side effect in HIV-1 infected patients. This complication can be stigmatizing in some affected patients and lead to reduced adherence to treatment, increased risk of cardiovascular complications and induce insulinoresistance. The pathophysiology of lipodystrophy remains poorly understood. Some antiretroviral drugs could be involved. Therefore, using PPAR G as a therapeutic target with the objective to reverse drug induced lipoatrophy appeared as a promising objective Thiazolidinediones are a new class of insulin sensitizing drugs for the treatment of type 2 diabetes. These PPARG agonist which mainly promote the differentiation of adipocytes, decrease circulating plasma free fatty acids. In non-HIV infected patients this class of drugs decreases intraabdominal fat accumulation and increases subcutaneous fat depot. Different previous studies were performed with that aim, most of them using rosiglitazone. We designed a prospective randomized, double blind placebo controlled multicentre study aiming to test the hypothesis that pioglitazone would improve lipoatrophy without deleterious effect on lipid profile in adult subjects receiving antiretroviral therapy.

Inclusion Criteria: 18 years of ages and older Confirmed laboratory diagnosis of HIV-1-infection Karnofsky equal or over 70% Patients treated with stable antiretroviral therapy for at least 6 months Plasma viral load below 400 copies/ ml and CD4 count over 200/mm3 for at least 6 months Patients with a clinical peripheral lipoatrophy self reported by the patient and confirmed by physical examination Exclusion Criteria: Cachexia Cardiac failure class3 or 4 at NYHA classification Acute opportunistic infection Pregnancy or breast-feeding Polynuclear neutrophils below 1000/mm3 Hemoglobin below 9 g/dl Platelets below 50 000/mm3 Creatinine level over 2 UN ASAT, ALAT over 2.5UN Bilirubin, amylase, lipase level over 2 UN CD4 count below 200/mm3 Patients treated by any antidiabetic or lipid lowering drugs, anabolic or corticosteroid hormone

Slama L, Lanoy E, Valantin MA, Bastard JP, Chermak A, Boutekatjirt A, William-Faltaos D, Billaud E, Molina JM, Capeau J, Costagliola D, Rozenbaum W. Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther. 2008;13(1):67-76.