Incidence and risk factors for mitochondrial toxicity in treated HIV/HCV-coinfected patients.
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)-alpha.


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 (ddl), ddl plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddl 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 ddl should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended.
Laguno
Montse
M
Infectious Diseases Unit, Hospital Clinic Barcelona, Barcelona, Spain. mlaguno@clinic.ub.es
Milinkovic
Ana
A
de Lazzari
Elisa
E
Murillas
Javier
J
Martínez
Esteban
E
Blanco
Jose Luis
JL
Loncá
Montse
M
Biglia
Alejandra
A
Leon
Agathe
A
García
Mercedes
M
Larrousse
Maria
M
García
Felipe
F
Miró
Jose Maria
JM
Gatell
Jose Maria
JM
Mallolas
Josep
J
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin