Ribavirin, an antiviral drug used in combination with alpha interferon to treat hepatitis C infection, appears to increase the risk of mitochondrial toxicity in HIV/hepatitis C co-infected individuals who are also receiving nucleoside analogue treatment for HIV, according to a report published today in The Lancet. In both cases, ddI and d4T were associated with serious toxicity when combined with ribavirin treatment.
Dr Alain Lafeuillade of Hospital Chalucet, Toulon, in France reported on two cases of serious mitochondrial toxicity in two patients who commenced treatment with ribavirin plus interferon alpha after a long period of stable nucleoside analogue treatment for HIV.
One patient had been taking AZT,ddI and saquinavir for three years when he commenced HCV treatment. One month later AZT was replaced with d4T due to the development of anemia; three months later liver enzyme, amylase and lactate elevations were noted, and over the next three months pancreatitis and diabetes developed and the patient lost 5kg in weight. Steatosis also progressed from 10% of hepatocytes to 50% of hepatocytes during this period. After the discontinuation of d4T and ddI and their replacement with AZT and 3TC, amylase and lipase levels returned to normal, as did the lactate/pyruvate ratio. The symptoms did not return when alpha interferon treatment was reintroduced.
In the second case, an individual with no problems tolerating ddI/d4T/3TC developed lactic acidemia, glucose intolerance and an increased level of hepatic steatosis during the six months following the introduction of alpha interferon/ribavirin treatment. The patient also lost 6kg in weight. After ribavirin treatment was stopped, lactate concentrations fell from 9.3mmol/L to 3.2mmol/L within two weeks (baseline level 2.8mmol/L).
A review of lactate and pyruvate changes in 15 HIV-infected and 10 non-HIV infected individuals after starting HCV treatment found that HIV-positive individuals were significantly more likely to experience increases in lactate (p=0.004) and pyruvate (p=0.003), and the researchers warn that clinicians should be alert for multiorgan mitochondrial toxicity in any co-infected patients receiving simultaneous treatment with nucleoside analogues and ribavirin.
Reference
Lafeuillade A et al. Increased mitochondrial toxicity with ribavirin in HIV/HCV coinfection. The Lancet 357: 280-281, 2001.