10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

A PATHOGENESIS PROPOSAL OF LIPOATROPHY REVERSIBILITY AFTER SWITCHING FROM THYMIDINE ANALOGUES TO TENOFOVIR

Antiviral Therapy 2008; 13(Suppl. 4):A37 (abstract no. P-20)

A Milinkovic, AI Garcia, I Perez, S Vidal, C Ayuso, M Laguno, A Leon, JL Blanco, M Martinez, M Lonca, M Larrousse, E Martinez, JM Gatell, X Tomas and J Mallolas
Hospital Clinic Barcelona, Barcelona, Spain

BACKGROUND: Multiple clinical trials have demonstrated that switching from thymidine analogues (TA) to tenofovir disoproxil fumarate (TDF)-containing regimens can benefit patients with lipid abnormalities or lipoatrophy. However, no pathogenical explanation has been given.

METHODS: A total of 29 HIV-infected patients with moderate to severe lipoatrophy, receiving stable antiretroviral therapy including TA (15 zidovudine and 14 stavudine) were prospectively switched to TDF, whereas the rest of their therapy remained unchanged. At baseline and 6 months after the switch, the biochemical markers (fasting plasma glucose, triglycerides, total cholesterol, high-denisty lipoprotein (HDL) and low-density lipoprotein cholesterol and venous lactate), leptin, adiponectin, insulin and resistin were measured. Furthermore, single-slice abdominal computed tomography (CT) scanning, dual energy X-ray absorptiometry (DEXA) body composition measurements and proton magnetic resonance spectroscopy (1H-MRS) of the soleus and tibialis anterior were performed.

RESULTS: As expected, 6 months after switching to TDF, a significant decrease was observed in triglycerides and total cholesterol values. Although peripheral and total fat content increased when measured by DEXA, peripheral and total lean mass decreased significantly (P=0.0007 and P=0.0004, respectively). Furthermore, these findings correlated with a significant increase in extramiocellular lipid (EMCL) content in the soleus (P=0.0289) and with an increase in EMCL and a decrease in intramiocellular lipid (IMCL) content in the tibialis anterior, although not significant, measured by 1H-MRS. The decrease in IMCL in the tibialis anterior at 6 months correlated significantly with an increase in HDL cholesterol (P=0.034) and adiponectin (P=0.042). The decrease of the IMCL values in the soleus correlated positively with triglyceride levels (P=0.047). All changes were observed irrespective of choice of TA at baseline.

CONCLUSIONS: Switching from thymidine analogues to TDF leads to significant reversal of peripheral lipoatrophy and lipid values improvement, whereas lean mass decreased when measured by DEXA. Correlations were observed between peripheral fat gain, loss of peripheral lean mass and decrease of IMCL and increase of EMCL lipid content.

Pathogenic mechanism of lipoatrophy reversal due to a switching to TDF might be explained by ‘migration’ of lipid content from IMCL to EMCL and to periphery, which may appear as a lean mass decrease when measured by DEXA.

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2008-11-06
P-20

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