Mitochondrial involvement in antiretroviral therapy-related lipodystrophy

Objectives: The management of HIV infection has greatly improved during rec ent years essentially because of the appearance of new antiretroviral drugs . Highly active antiretroviral therapy (HAART) has achieved important reduc tions of viraemia and significant recoveries of CD4(+) cell counts in HIV-i nfected patients. Nonetheless, cases of HIV-infected individuals experienci ng lipodystrophy (LO are being increasingly reported. The purpose of this w ork was to analyse whether the presence of mitochondrial abnormalities is a frequent feature in LD, since we previously detected mitochondrial abnorma lities in an HIV-patient. The second main objective was to study whether LD could be associated with a specific drug. Design: Seven HIV patients presenting LID and five HIV non-LD controls part icipated in the study. LID patients met the following criteria: (1) LID was their only clinical abnormality, (2) LD was clinically relevant, (3) compl iance with antiretroviral treatment was higher than 90% and (4) patients di d not have personal or familial history suggestive of mitochondrial disease or neuromuscular disorder. Methods: Histological stainings, histo-enzymatic reactions, enzymatic and r espiratory activities of mitochondrial respiratory chain complexes, and mit ochondrial DNA (mtDNA) depletion and rearrangements were examined on muscle mitochondria. Results: Structural muscle abnormalities, mitochondrial respiratory chain d ysfunction or mtDNA deletions were detected in all HIV lipodystrophic patie nts. Conclusions: The mitochondrial abnormalities found suggest that mitochondri al dysfunction could play a role in the development of antiretroviral thera py-related lipodystrophy. (C) 2001 Lippincott Williams & Wilkins.