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New-Onset Diabetes Mellitus Associated with Use of Protease Inhibitor
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TO THE EDITOR:
The use of protease inhibitors has revolutionized the treatment of HIV infection through the ability of these drugs to decrease viral load [1]. Although these agents are fairly well tolerated, previously unrecognized adverse reactions will become more evident as the availability of the drugs improves and use becomes more widespread. New-onset diabetes mellitus has been described with several agents commonly used to manage HIV disease [2-4]. We noted a strong temporal relation between the onset of hyperglycemia and the initiation or change in protease inhibitor therapy in five HIV-infected patients.
The Table 1 shows the characteristics of these patients. All were known to have had HIV infection for more than 5 years, and all experienced disease progression despite extensive use of nucleoside analogues. Before protease inhibitor therapy began, the mean CD4+ count was 87 cells/mm3, and viral loads ranged from 7000 to 355 000 copies/mL. None of the patients had risk factors for diabetes, although one had had elevated random blood glucose levels before treatment. None of the patients had received pentamidine or megestrol. At the time of hyperglycemia onset, the mean CD4+ count had increased to 224 cells/mm3 and the mean decrease in viral load was 128 000 copies/mL.
Hyperglycemia was controlled without difficulty through either oral hypoglycemic agents or diet modification and did not necessitate discontinuation of therapy with the protease inhibitor. None of the patients developed diabetic ketoacidosis, and only one patient required hospitalization for glycemic control. In one case, withdrawal of protease inhibitor therapy resulted in correction of hyperglycemia; subsequent rechallenge caused recurrence.
The mechanism by which hyperglycemia occurs in association with protease inhibitor use is unclear. Discontinuation of therapy with the drug, which may promote viral resistance [5], is not necessary for glycemic control. Until more data are available, clinicians who treat HIV-infected patients must be aware that protease inhibitors can cause hyperglycemia in patients with or without a history of glucose intolerance.
John A. Eastone, MD
Catherine F. Decker, MD
National Naval Medical Center; Bethesda, MD 20889
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
