didanosine and Liver-Failure

The combination of tenofovir and didanosine results in an increase in the didanosine plasma exposure and might augment the risk for didanosine toxicity. Although pharmacokinetic studies support a didanosine dose reduction to 250 mg when used concurrently with tenofovir in patients weighing at least 60 kg, no data are available in lower-weight patients. We describe a case of lactic acidosis and acute liver failure in a low-weight patient receiving tenofovir and a reduced dose of didanosine (200 mg/day). To our knowledge, this is the first case of severe toxicity associated with a reduced dose schedule of didanosine. Previous cases of severe toxicity associated with the combination of tenofovir and didanosine are reviewed.

Topics: Acidosis, Lactic; Acute Disease; Adenine; Anti-HIV Agents; Didanosine; Drug Therapy, Combination; Female; HIV Infections; HIV-1; Humans; Liver Failure; Male; Middle Aged; Organophosphonates; Reverse Transcriptase Inhibitors; Tenofovir

Severe hepatotoxicity is a rare but potentially life-threatening side effect of antiretroviral therapy. In this case report we describe an HIV-positive patient who was admitted to our clinic with evidence of severe acute pancreatitis 18 months after the introduction of antiretroviral treatment, which included stavudine and didanosine. Shortly afterwards, she developed lactate acidosis and acute hepatic failure associated with renal failure. Renal support (hemofiltration) was required for three days. The patient subsequently developed grade III encephalopathy, as well as a large pleural effusion and ascites. Although the reported outcome of patients with liver failure due to antiretroviral treatment is poor, with a high mortality rate, our patient fully recovered after intensive supportive care and cessation of the antiretroviral agents. Liver biopsy revealed microvesicular steatosis and giant mitochondria, which are the typical hallmarks of mitochondrial damage, the presumed mechanism of antiretroviral drug toxicity. More than three years later the patient has an excellent clinical status with a stable HIV infection and no need for antiretroviral treatment. This case report indicates the need for increased awareness of the potential hepatotoxicity of an antiretroviral therapy, as severe side effects may occur more frequently with increasing use of such treatment.

Topics: Acidosis, Lactic; Acute Disease; Adult; Anti-HIV Agents; Biopsy; Critical Care; Didanosine; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Infections; Humans; Liver; Liver Failure; Pancreatitis; Reverse Transcriptase Inhibitors; Stavudine; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography; Zidovudine

As the prevalence of human immunodeficiency virus (HIV) infection continues to rise the clinician is encountered with a diagnostic challenge. Nonsurgical diseases such as acute colitis or enteritis can appear similar to such true surgical emergencies as abscess, perforation, or mesenteric ischemia. We report a case of fulminant hepatic failure associated with didanosine and masquerading as a surgical abdomen and compare the clinical, biologic, histologic, and ultrastructural findings with reports described previously. This entity should be kept in mind when evaluating the acute abdomen in the HIV-positive patient.

Topics: Abdomen, Acute; Acidosis, Lactic; Adult; Anti-HIV Agents; Diagnosis, Differential; Didanosine; Fatty Liver; Female; HIV Infections; Humans; Liver; Liver Failure

Topics: Anti-HIV Agents; Didanosine; Fatal Outcome; HIV Infections; HIV-1; Humans; Liver Failure; Male; Middle Aged; Stavudine