First report of abacavir associated with hypoglycemia

Abstract

The nucleoside reverse transcriptase inhibitor abacavir has not previously been associated with hypoglycemia but there are reports in the literature with hyperglycemia [1]. We describe a 41-year-old woman diagnosed with HIV infection in 2000. She was started on Combivir (zidovudine/lamivudine) and nelfinavir in 2001 when her CD4 cell count was 197 cells/mm3. She responded to this treatment with undetectable viral loads and an appropriate rise in CD4 cell counts. She was diagnosed with diabetes mellitus in February 2007 when her random blood glucose was 27.3 mmol/l requiring insulin treatment. In November 2007, it was felt zidovudine was contributing to her chronic anemia (hemoglobin 112 g/l). Her HLA-B*5701 test was negative and the decision was made to change to Kivexa (abacavir/lamivudine) and continue on nelfinavir. No other medication changes were made and she denied any herbal medication use. Ten days following the change, she reported symptomatic and documented hypoglycemic episodes (glucose nadir:1.8 mmol/l) for 2 days despite frequent snacks every 2–4 h. Her exogenous insulin was discontinued but she continued to experience hypoglycemia. Investigations revealed a normal serum insulin level, C-peptide, thyroid-stimulating hormone, serum and urine cortisol, adrenocorticotropic hormone stimulation test, growth hormone levels, and cyclic citrullinated peptide antibody (Table 1). Her insulin autoantibody level was elevated (12 μU/ml). MRI of the abdomen revealed no evidence of insulinomas or other abnormalities. Although lamivudine has been associated with grade III or IV hypoglycemia [2], we felt that this was unlikely to be the cause given the long-term treatment with lamivudine. We were concerned about the newly initiated abacavir. In March 2008, her abacavir was discontinued and replaced with tenofovir, whereas she remained on lamivudine and nelfinavir. Her hypoglycemic episodes resolved 4 days after discontinuing abacavir. She continues to remain euglycemic despite lack of insulin or oral hypoglycemic medications. At her last follow-up visit, her viral load remained undetectable and her CD4 cell count was 920 cells/mm3 (34%).Table 1: Laboratory values near the time of treatment with abacavir.Abacavir has been in clinical use for the treatment of HIV since the late 1990s [3]. It has been proven to have a low adverse event profile in individuals who are HLA-B*5701 negative [4]. This is the only case of abacavir-associated hypoglycemia in our clinic and, to our knowledge, the first reported case in the literature. Given the temporal relationship of hypoglycemic episodes with the addition of abacavir and resolution following its discontinuation, it is difficult to implicate another cause. As we cannot postulate a biological mechanism for this reaction, we realize the need to be vigilant of other patients who may experience similar symptoms. Acknowledgements Contributed to patient care are O.E.L., K.K., and M.L.B. O.E.L., K.K., and M.L.B analyzed the data. O.E.L. wrote the paper. O.E.L., K.K., and M.L.B edited the manuscript. All authors read and approved the final manuscript. There are no conflicts of interest. No financial support was received for this work.