Hyperlactatemia due to Nevirapine

Background: Hyperlactatemia is a well-known adverse reaction in HIV-infected patients who are treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) (1). However, data on its association with the other 2 widely used classes of antiretroviral agents, nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors, are inconclusive. To our knowledge, no cases of hyperlactatemia secondary to nevirapine use have been reported to date. Objective: To describe a patient with nevirapine-induced hyperlactatemia who gradually recovered after cessation of treatment. Methods and Findings: A 36-year-old man received a diagnosis of HIV infection in November 2000 and began receiving azidothymidine-lamivudine-nevirapine in January 2001. He tolerated the treatment well for 20 months, achieving suppression of the viral load to undetectable levels and an increase in CD4 + cell count to 1.506 X 10 9 cells/L. He then began to report nausea, fatigue, dyspnea, and pain in the epigastrium. He did not take any other prescription or over-the-counter medication. On admission, he was slightly tachypneic (20 breaths/min), and physical examination was notable only for mild epigastric tenderness. Laboratory work-up showed mildly elevated aminotransferase levels (aspartate aminotransferase level, 44 U/L [normal range, 7 to 40 U/L]; alanine aminotransferase level, 64 U/L [normal range, 7 to 40 U/L]), elevated triglyceride level (3.03 mmol/L [268 mg/dL] [normal range, 0.57 to 1.69 mmol/L {50 to 150 mg/dL}]), elevated cholesterol level (8.21 mmol/L [317 mg/dL] [normal range, <4.92 mmol/L [<190 mg/dL}]), and a lactate level of 13.1 mmol/L (normal range, 0.6 to 2.4 mmol/L) with mild metabolic acidosis (pH level, 7.34; HCO 3 level, 18.3 mmol/L). Results of serologic tests for hepatitis B and C viruses were negative. An extensive investigation ruled out other pathologic conditions that could lead to hyperlactatemia. Empirical therapy consisted of withdrawal of the antiretrovirals and administration of L-carnitine and a multivitamin tablet containing thiamine and vitamin B 6 (2, 3). Three weeks later, the patient had marked clinical improvement and a gradual decrease in lactate level to 5 mmol/L. At this time, and because of an increase in viral load, nevirapine-saquinavir-ritonavir treatment was administered (eliminating the NRTIs azidothymidine and lamivudine) and the cofactors supplementation was continued. Six weeks later, symptoms recurred and were accompanied by an increase in lactate level to 12.1 mmol/L. Finally, the antiretroviral regimen was changed to saquinavir-lopinavir-ritonavir. The lactate level normalized (despite withdrawal of the vitamins), which persisted up to the last follow-up visit in December 2005. The Figure shows the progression of the lactate level over time and its association with the therapeutic interventions. Conclusions: We present what we believe is the first well-documented case of hyperlactatemia associated with the use of the NNRTI nevirapine. In fact, determination of Naranjo and colleagues' probability scale (4) reveals a score of 9, indicating a "highly probable" adverse event.