Mitochondrial Abnormalities in HIV-Infected Lipoatrophic Patients Treated With Antiretroviral Agents
| Autor: | Jean-Pierre Hespel, Pierre Rochcongar, Christian Michelet, Régis Duvauferrier, Faouzi Souala, Jean-Marc Begue, Françoise Chapon, Pierre Tattevin, Cécile Bouvier, Jocelyne Beillot, Cédric Arvieux, Mathieu Dupont, Jean-Marc Chapplain |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
medicine.medical_specialty Mitochondrial Diseases Lipodystrophy Respiratory chain HIV Infections Biology Gastroenterology Absorptiometry Photon Internal medicine Immunopathology Biopsy medicine Humans Pharmacology (medical) Lipoatrophy Aged Aged 80 and over medicine.diagnostic_test Middle Aged medicine.disease Pathophysiology Mitochondria Muscle Regimen Infectious Diseases Anti-Retroviral Agents Lactic acidosis Immunology Reverse Transcriptase Inhibitors Acidosis Lactic |
| Zdroj: | JAIDS Journal of Acquired Immune Deficiency Syndromes. 37:1477-1488 |
| ISSN: | 1525-4135 |
| DOI: | 10.1097/01.qai.0000138982.68106.6c |
| Popis: | BACKGROUND: Lipodystrophy is now widely described in HIV infected patients under antiretroviral regimen with important psychological impact. But physiopathology of loss of fat mass is still debated and the role of mitochondrial impairment is not clearly defined. OBJECTIVE: To correlate clinical lipoatrophy (LA) in HIV patients with long-term treatment by nucleoside reverse transcriptase inhibitors (NRTIs) and muscular impairment related to mitochondrial dysfunction. METHODS: Ten consecutive patients with clinical LA and 10 nonlipodystrophic (NLD) individuals on antiretroviral therapy were included. Patients underwent the following investigations: dual-energy x-ray absorptiometry (DEXA) scanning and lactate kinetics during standardized exercise. The mitochondrial respiratory complex activity (III and IV) and histoenzymatic abnormalities (classified as none, mild, or severe) were evaluated on muscle tissue obtained by biopsy in deltoid muscle. RESULTS: Mean NRTI exposure was longer in the LA group than in the NLD group (81 +/- 30 months vs. 59 +/- 15 months), but mean protease inhibitor exposure was identical in both groups. Mean fat mass distribution for leg in the LA and NLD groups was 860 +/- 381 g versus 1895 +/- 999 g, respectively. The lactic acidosis threshold during exercise was reached in the LA group at lower workloads (mean: 45 +/- 17 W in the LA group vs. 68 +/- 11 W in the NLD group), and maximum power output exercise was restricted in LA patients (mean: 115 +/- 30 W vs. 153 +/- 28 W). Total complex activities in muscular tissue were lower in LA patients: the median (range) for complex III was 67 (1-128) versus 112 (28-143), and the median (range) for complex IV was 28 (1-70) versus 42 (1-75). Six patients had severe histoenzymatic abnormalities in the LA group versus none in the NLD group. CONCLUSION: Clinical LA, confirmed by DEXA, in long-term NRTI-treated patients was associated with muscular mitochondrial dysfunction as shown by rapid lactic acidemia increase, impairment of respiratory chain activity for complexes III and IV, and mitochondrial histoenzymatic abnormalities. |
| Databáze: | OpenAIRE |
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