Metabolic Acidosis and Hepatic Steatosis in Two HIV-Infected Patients on Stavudine (d4T) Treatment

• Published in: Archives of medical research 2003, Vol.34 (1), p.64-69
• Main Authors: Cornejo-Juárez, Patricia, Sierra-Madero, Juan, Volkow-Fernández, Patricia
• Format: Article
• Language: English
• Subjects: Acidosis, Lactic - chemically induced; Adult; Aged; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Fatal Outcome; Fatty Liver - chemically induced; Female; HIV; HIV Infections - drug therapy; Humans; Lactic acidosis; Liver steatosis; Male; Middle Aged; Nucleoside reverse transcriptase inhibitors; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - therapeutic use; Stavudine; Stavudine - adverse effects; Stavudine - therapeutic use
• ISSN: 0188-4409; 1873-5487
• DOI: 10.1016/S0188-4409(02)00454-X

Nucleoside analog reverse transcriptase inhibitors (NRTI) have been used to treat HIV-infected patients for >10 years. Some severe adverse events have been attributed to mitochondrial dysfunction. Since 1991, cases of severe lactic acidosis have been reported in association with nucleoside therapy. Our objective was to report two cases of metabolic acidosis and hepatic steatosis in patients receiving stavudine (d4T) and to review the literature. A male and a female, 47 and 45 years of age, respectively, presented with abdominal pain, nausea, vomiting, and weakness after 9 and 6 months, respectively, of treatment with stavudine. At presentation, both patients had severe metabolic acidosis and liver failure. Ultrasonography showed hepatic steatosis (confirmed by biopsy in one case). All antiretroviral drugs were withdrawn and patients were treated with bicarbonate. Both patients developed fulminant liver dysfunction and multiple organ failure. We reviewed the literature and found 75 cases of lactic acidosis and hepatic steatosis associated with use of NRTI; 57 of these patients received d4T (76%). Of all cases reported in association with nucleoside therapy, 63% were females and mortality was 47%. General weakness, hepatic enzyme elevation, and liver steatosis are data that should alert physicians to this serious adverse event and to respond with prompt interruption of antiretroviral drugs and measurement of lactic acid in plasma. It is important to report serious adverse events in commercially released drugs to know prevalence in an exposed population. Physicians should be aware of risk and early signs of this serious adverse event.