Use of ddI/d4T with hepatitis C treatment raises risk of mitochondrial toxicity

Using ddI/d4T alongside ribavirin in HIV/HCV co-infected patients can lead to substantial weight loss, probably due to mitochondrial toxicity, according to a report in today’s edition of the New England Journal of Medicine.

47 patients coinfected with HCV and HIV who had received interferon alpha and ribavirin at the same time as antiretroviral therapy were analysed. Individuals lost an average of 3.7kg in the first three months of therapy, and this weight loss persisted to the end of the six month treatment period. Weight loss was accompanied by an upward trend in lactate and amylase levels. Since elevations in both lactate and amylase may be consequences of mitochondrial toxicity caused by nucleoside analogues, and a trend towards higher lactate and amylase levels and greater weight loss was seen in patients treated with ddI and/or d4T, the authors suggest that weight loss is a consequence of an interaction between ribavirin and one of these drugs, and is another sign of mitochondrial toxicity.

“We have not, in our clinical experience, observed comparable weight loss in patients taking interferon plus ribavirin alone or in those taking antiretroviral drugs” said Dr Teresa Garcia-Benayas of the Instituto de Salud Carlos III in Madrid.

A similar pattern was reported in the RIBAVIC study, a French trial of interferon alpha or pegylated interferon with ribavirin in co-infected individuals. Reported at last month’s 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy in San Diego, the analysis of 265 individuals showed that 22% of patients (9/41) receiving ddI and d4T and ribavirin developed hyperlactatemia or pancreatitis, both recognised symptoms of mitochondrial toxicity. This translated into a 24-fold higher risk of mitochondrial toxicity compared to patients who did not receive ddI/d4T (p