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Session 148 Poster Abstracts
Fat Redistribution: Novel Therapies and Switch Studies
Thursday, 1:30 - 3:30 pm
Hall B


860    
Improvement of Subcutaneous Fat, Lipid Profile, and Parameters of Mitochondrial Toxicity in Patients with Peripheral Lipoatrophy when Stavudine Is Switched to Tenofovir. The LIPOTEST Study
Esteban Ribera*, J Paradineiro, S Sauleda, E Garcia Arumi, S Luque, V Falco, X Serres, R Comet, M Crespo, A Andreu, R Marti, I Ocana, D Sureda, and A Pahissa
Hosp Vall d'Hebron, Barcelona, Spain

Background:  Stavudine (d4T)-associated mitochondrial toxicity may play a role in the etiology of lipoatrophy. We hypothesised that switching from d4T to tenofovir (TDF) will result in an increase in mtDNA in peripheral blood mononuclear cells (PBMC) and an improvement in lipid profile and peripheral lipoatrophy.

Methods:  We enrolled 53 subjects with HIV-1 RNA < 50 copies/mL on d4T-based ART regimens with lipoatrophy. While the other drugs were maintained, d4T was switched to TDV, and patients were prospectively followed. Fasting plasma samples were obtained for measuring lipid profile and lactatemia. A real-time PCR assay was used to quantify mtDNA/nDNA ratio in PBMC. Fat mass and subcutaneous malar fat thickness were determined by bioelectrical impedance analysis and sonography, respectively.

Results:  Baseline characteristics were:  mean age of 40 years, 68% male, median CD4 count 434 cells/µL. After 18 months of TDV therapy in no case was TDV withdrawn for adverse effects or virologic failure. Two patients with virologic failure had virus isolates remaining sensitive to TDV. No significant differences occurred in CD4 cell count. Median values of lactate levels, mtDNA ratio, lipidic profile, and fat mass and malar fat (Bichat) thickness are shown in the table.

 

Parameter

Baseline

Month 6

Month 12

Month 18

Lactate (mM/L)

PBMC mtDNA

Cholesterol (mg/dL)

Triglycerides (mg/dL)

Fat (kg)

Malar fat

thickness (mm)

1.7 (1.1–2.7)

42 (32–63)

225

(172–262)

264

(145–497)

18.4 (14–23)

2.9 (2.6–4.1)

1.3 (0.8–1.7)*

57 (39–79)

195

(161–230)*

205

(123–334)*

19.2 (14–25)

3.1 (2.4–3.6)

1.2 (0.9–1.7)*

57 (44–78)

202

(156–230)*

209

(119–414)*

20.2 (16–26)*

3.1 (2.3–3.9)

1.1 (0.8–1.8)*

66 (45–112)

206

(155–246)*

212

(130–368)*

21.2 (16–26)*

3.7 (2.8–4.1)*

*p < 0.05 compared to baseline (Wilcoxon test).

  Results expressed as median (CI 95%).

 

Conclusions:  Switching from d4T to TDF was well-tolerated and virologic and immunologic success was maintained. Patients showed a rapid improvement of the lipid profile, decrease in lactate levels and a slight amelioration of mtDNA content in PBMC. In addition, they presented a slow but significant recovery of the fat mass and the malar fat thickness.

 

 

Keywords: switch therapy; peripheral lipoatrophy; mitochondrial toxicity