Tesamorelin: A hope for ART-induced lipodystrophy
Notice bibliographique
Résumé
Sir, One of the complications of long-term antiretroviral therapy (ART) is the development of lipodystrophy in the patients. Lipodystrophy is a metabolic condition characterized by insulin resistance, fat redistribution, and hyperlipidemia.[1] The condition is seen in about 10 to 40% individuals taking long-term antiretroviral therapy for HIV infection. In virally infected patients, lipodystrophy can lead to increased risk of myocardial infarction and other cardiovascular complications.[2] In November 2010, the United States Food & Drug Administration (USFDA)-approved tesamorelin, under the trade name Egrifta™, for the treatment of lipodystrophy in HIV-infected individuals. Tesamorelin has been developed by Theratechnologies Inc., a Canadian company. It is a stabilized synthetic peptide analogue of the hypothalamic peptide, Growth Hormone Releasing Hormone (GHRH). Tesamorelin is required to be given a daily subcutaneous injection in a dose of 2 mg for the improvement of body image. By acting on the pituitary cells in the brain, tesamorelin stimulates production and release of the endogenous hormone.[3] The pharmacokinetics of tesamorelin show that it has low oral bioavailability and the pharmacokinetic parameters vary highly among individuals. However, no difference has been observed in patients on antiretroviral therapy from that of healthy adult individuals. The data from Phase III clinical have shown that in HIV-infected patients with excess abdominal fat, tesamorelin treatment for 26 weeks significantly decreased visceral adipose tissue (VAT) fat without any changes on limb or subcutaneous adipose tissue (SAT) fat.[4] At 52 weeks, VAT losses continued and SAT was preserved. The important finding during this phase was that insulin-like growth factor-I increased and triglyceride levels fell down, suggesting an improvement in insulin resistance. Tesamorelin therapy predisposes to glucose intolerance and can also increase the risk of type 2 diabetes. So, the drug is contraindicated during pregnancy. It is further contraindicated in patients with disruption of hypothalamic pituitary axis due to some or the other reason. Some serious side-effects observed with tesamorelin therapy include neuropathies, lipoatrophy, diarrhea with fever and dehydration, congestive heart failure, etc. Diarrhea, congestive heart failure, peripheral neuropathy, and loss of mobility were the four serious adverse events reported during the clinical studies. IgG antibodies against tesamorelin were detected in about 50% of the patients being treated by the drug. However, as soon as the treatment was stopped, IgG titer levels against tesamorelin decreased. No change in response was observed in patients with or without antibodies. The investigators found the incidence of urticaria in some patients (2.2%) who were sensitive to tesamorelin. Other symptoms of hypersensitivity to tesamorelin included tachycardia, shortness of breath, sweating, and erythema.[5] Food does not interfere with tesamorelin pharmacokinetics and normal diet can be continued with treatment. Studies with CYP3A inhibitors and substrates have shown that tesamorelin has minimal effects on CYP3A. So, agents affected by CYP3A and affecting CYP3A can be coadministered with tesamorelin. Thus, the development of tesamorelin has not raised any concerns which are clinically significant. It was concluded that subcutaneous 2 mg OD administration of tesamorelin is well tolerated.[6] Any distressing observations can be easily dealt with, without causing much of patient discomfort. Tesamorelin thus offers the patients of HIV infection and the physicians a first-rate choice in the management of associated lipodystrophy and also improves the quality of life.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
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| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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