Ribavirin and Didanosine Therapy
Ribavirin and Didanosine Therapy
Pancreatitis and lactic acidosis are severe and life-threatening adverse events associated with nucleoside analogue antiretroviral therapy used to treat HIV infection. The drug from this class most commonly associated with these adverse events is stavudine, although zidovudine and didanosine have also been implicated. Ribavirin is a nucleoside analogue used in combination with interferon alfa to treat hepatitis C. Because of similar mechanisms of action, the combination of these 2 drugs could potentially increase such toxicity. A case of fatal lactic acidosis and pancreatitis is described in an HIV-infected patient coinfected with hepatitis C on a didanosine-containing antiretroviral regimen after treatment of hepatitis C was initiated with ribavirin and pegylated interferon alfa-2b. Extreme caution should be exercised when didanosine and ribavirin are used concomitantly because of the increased risk of mitochondrial toxicity and the syndrome of severe metabolic acidosis with elevated lactic acid levels.
Nucleoside analogues are an important backbone of HAART, the use of which has led to a significant decline in the mortality associated with HIV disease. While efficacious, drugs from this class are associated with significant and sometimes life-threatening adverse events. Stavudine, zidovudine, and didanosine have been associated with mitochondrial dysfunction and a syndrome of severe pancreatitis and lactic acidosis. The presumed mechanism of mitochondrial toxicity is via inhibition of DNA polymerase
, leading to a depletion of mitochondrial DNA.
Therapy for hepatitis C virus (HCV) infection with interferon alfa and ribavirin has also been associated with lactic acidosis. In some cases, the lactic acidosis and pancreatitis are associated with unexplained multiorgan failure and death. Since HCV coinfection is highly prevalent in HIV-infected patients and HIV-infected patients are living longer, more of these patients may be expected to be treated for hepatitis C.
Optimal treatment of hepatitis C requires a combination of interferon alfa and ribavirin, so it is inevitable that some patients with HIV-HCV coinfection would receive 1 or more nucleoside analogues and ribavirin concomitantly. Any potential toxicity of such a combination needs to be evaluated carefully, and if an additive or synergistic toxicity is found, the combination should be avoided.
Pancreatitis and lactic acidosis are severe and life-threatening adverse events associated with nucleoside analogue antiretroviral therapy used to treat HIV infection. The drug from this class most commonly associated with these adverse events is stavudine, although zidovudine and didanosine have also been implicated. Ribavirin is a nucleoside analogue used in combination with interferon alfa to treat hepatitis C. Because of similar mechanisms of action, the combination of these 2 drugs could potentially increase such toxicity. A case of fatal lactic acidosis and pancreatitis is described in an HIV-infected patient coinfected with hepatitis C on a didanosine-containing antiretroviral regimen after treatment of hepatitis C was initiated with ribavirin and pegylated interferon alfa-2b. Extreme caution should be exercised when didanosine and ribavirin are used concomitantly because of the increased risk of mitochondrial toxicity and the syndrome of severe metabolic acidosis with elevated lactic acid levels.
Nucleoside analogues are an important backbone of HAART, the use of which has led to a significant decline in the mortality associated with HIV disease. While efficacious, drugs from this class are associated with significant and sometimes life-threatening adverse events. Stavudine, zidovudine, and didanosine have been associated with mitochondrial dysfunction and a syndrome of severe pancreatitis and lactic acidosis. The presumed mechanism of mitochondrial toxicity is via inhibition of DNA polymerase
, leading to a depletion of mitochondrial DNA.
Therapy for hepatitis C virus (HCV) infection with interferon alfa and ribavirin has also been associated with lactic acidosis. In some cases, the lactic acidosis and pancreatitis are associated with unexplained multiorgan failure and death. Since HCV coinfection is highly prevalent in HIV-infected patients and HIV-infected patients are living longer, more of these patients may be expected to be treated for hepatitis C.
Optimal treatment of hepatitis C requires a combination of interferon alfa and ribavirin, so it is inevitable that some patients with HIV-HCV coinfection would receive 1 or more nucleoside analogues and ribavirin concomitantly. Any potential toxicity of such a combination needs to be evaluated carefully, and if an additive or synergistic toxicity is found, the combination should be avoided.