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Didanosine plus ribavirin can be toxic in HIV patients treated for hepatitis C
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By David Douglas
NEW YORK (Reuters Health) - The use of didanosine in HIV patients receiving hepatitis C virus (HCV) therapy with interferon and ribavirin increases the risk of symptomatic mitochondrial toxicity, according to French researchers.
"Clinicians should be aware of the potential overlapping toxicity of treatments for HCV and HIV infection," lead investigator Dr. Firouze Bani-Sadr told Reuters Health. "If the two treatments must be administered concomitantly, didanosine should be avoided. Ribavirin is known to enhance didanosine phosphorylation. "
In the September 1st issue of the Journal of Acquired Immunodeficiency Syndromes, Dr. Bani-Sadr of Hopital Saint Antoine, Paris and colleagues note that there have been reports that HCV therapy can cause symptomatic mitochondrial toxicity in HIV patients receiving highly active antiretroviral therapy.
To evaluate associated risk factors, the researchers reviewed data on HIV and HCV coinfected patients taking part in a trial of interferon and ribavirin treatment.
Eleven of 283 patients who received at least one dose of HCV treatment developed symptomatic mitochondrial toxicity. This manifested itself as symptomatic hyperlactatemia in six patients and pancreatitis in five patients.
The overall incidence was 47.5 per 1000 patient-years. In patients receiving didanosine, however, the incidence was 200.2 per 1000 patient-years. With didanosine, there was a 46-fold increase in the relative risk of symptomatic mitochondrial toxicity. No increase was seen in patients on regimens that did not contain didanosine.
Given these findings, the researchers conclude that coadministration of ribavirin and didanosine should be avoided, "if unavoidable," they add, "patients should be monitored closely for signs of mitochondrial toxicity."
J Acquir Immune Defic Syndr 2005;40:47-52.
Study finds ddI but not d4T associated with risk for symptomatic mitochondrial toxicity in RIBAVIC during IFN/RBV therapy
"Risk Factors for Symptomatic Mitochondrial Toxicity in HIV/Hepatitis C Virus-Coinfected Patients During Interferon Plus Ribavirin-Based Therapy"
JAIDS Journal of Acquired Immune Deficiency Syndromes: Volume 40(1) 1 September 2005
Bani-Sadr, Firouze MD*; et al, The ANRS Hc02-Ribavic Study Team From the *Groupe Hospitalier Universitaire Est, Universite Paris 6, INSERM U444, Paris, France.
.... coadministration of ribavirin and ddI should be avoided; if unavoidable, patients should be monitored closely for signs of mitochondrial toxicity.....
".....We found that concomitant ddI therapy in patients receiving both IFN (standard or pegylated) and ribavirin was associated with an adjusted 46-fold increase in the risk of symptomatic mitochondrial toxicity compared with patients receiving antiretroviral regimens that did not contain ddI..... In our study the incidence of symptomatic mitochondrial toxicity was not significantly different between patients who were taking both ddI and d4T and those taking ddI alone or combined with NRTIs other than d4T. No cases were observed among patients treated with d4T without ddI, or with a triple-NRTI combination without ddI.... In our patients, the clinical manifestations usually consisted of weight loss, weakness, nausea, and abdominal pain and were therefore indistinguishable from common adverse effects of IFN-ribavirin combination therapy.1,2 Serum lactate and lipase should therefore be assayed in patients presenting with these manifestations or with more acute symptoms. Attention must also be paid to gradually increasing GGT levels, as this is not a common effect of HCV infection. As in previously reported cases of symptomatic mitochondrial dysfunction, we noted a gradual significant increase in GGT levels (mean 14.35, range 6-30 upper limit of normal (ULN) in 6 of our patients... (see below for further details & analysis regarding toxicity & NRTIs in this study).
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