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Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens

Tungsiripat, Marisaa,1; Bejjani, Dalia Elb,c,1; Rizk, Nesrinec; O'Riordan, Mary Annc; Ross, Allison Cc; Hileman, Corrilynnc; Storer, Normac; Harrill, Daniellec; McComsey, Grace Ac

doi: 10.1097/QAD.0b013e328339e274
Clinical Science

Objective: Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-γ and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-γ agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy.

Design: This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment.

Methods: Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed.

Results: We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (−100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups.

Conclusion: In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.

aCleveland Clinic, USA

bMetrohealth Medical Center, USA

cCase Western Reserve University, and University Hospitals Case Medical Center, Cleveland, Ohio, USA.

1These authors contributed equally to the work.

Received 8 January, 2010

Revised 25 February, 2010

Accepted 8 March, 2010

Correspondence to Grace A. McComsey, MD, FIDSA, Professor of Pediatrics and Medicine, Case School of Medicine, Cleveland, OH 44106, USA. Tel: +1 216 844 3607; fax: +1 216 844 8362; e-mail: Grace.mccomsey@case.edu

© 2010 Lippincott Williams & Wilkins, Inc.