Incidence and risk factors for mitochondrial toxicity in treated HIV/HCV-coinfected patients
| Autor: | Mercedes Garcia, Alejandra Biglia, Maria Larrousse, Montse Loncá, Elisa de Lazzari, Ana Milinkovic, Agathe León, José M. Gatell, Esteban Martínez, Javier Murillas, Felipe García, Montse Laguno, José L. Blanco, Josep Mallolas, José M. Miró |
|---|---|
| Předmět: |
Adult
Male Mitochondrial Diseases Hepatitis C virus Hepacivirus HIV Infections Interferon alpha-2 medicine.disease_cause Antiviral Agents Drug Administration Schedule Flaviviridae Acquired immunodeficiency syndrome (AIDS) Risk Factors Antiretroviral Therapy Highly Active Ribavirin medicine Humans Pharmacology (medical) Prospective Studies Risk factor Sida Pharmacology biology business.industry Interferon-alpha medicine.disease biology.organism_classification Hepatitis C Recombinant Proteins Mitochondrial toxicity Infectious Diseases Immunology Drug Therapy Combination Female Viral disease business |
| Zdroj: | ResearcherID Scopus-Elsevier Europe PubMed Central |
| Popis: | Background Coinfection with hepatitis C virus (HCV) and HIV is not uncommon and therapies for both infections are currently available. A major drawback, however, could be a potentially higher risk for mitochondrial toxicity (MT), defined as the elevation of pancreatic enzymes or lactate levels due to the nucleoside analogue reverse transcriptase inhibitors contained in both therapies. Methods Prospective analyses of clinical and laboratory data, including plasma lactate levels and pancreatic enzymes, of 113 consecutive HIV/HCV-coinfected patients were assigned to receive ribavirin (RBV) plus interferon (IFN)-α. Results Fourteen patients (12%) showed increased levels of amylase/lipase and/or hyperlactataemia. No patient developed clinical pancreatitis. Four patients with hyperlactataemia had clinical symptoms of lactic acidosis and recovered uneventfully by 2 weeks after treatment withdrawal. The variables significantly associated with MT in the univariate analysis were: therapy with didanosine (ddI), ddI plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddI use was the only independent risk factor for MT identified in the multivariate analysis. MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors. Conclusions 12% of HIV/HCV-coinfected patients receiving IFN plus RBV concomitantly with highly active antiretroviral therapy developed laboratory markers of MT. Although most of cases were asymptomatic, our study suggests that concomitant use of RBV plus ddI should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|