Autoimmune diabetes in HIV-infected patients on highly active antiretroviral therapy.

Abstract

Various autoimmune diseases, especially autoimmune thyroid disease, are known to occur in HIV-infected patients on highly active antiretroviral therapy (HAART). However, no reports have described the development of autoimmune diabetes during HAART. Our objective was to investigate the clinical course of the development of autoantibodies and diabetes during HAART. Based on their high antiislet autoantibody titers and requirement for insulin therapy, we diagnosed three HIV-infected patients with autoimmune diabetes. To clarify the relationship between the development of an autoimmune reaction against pancreatic beta-cells and recovery of CD4+ T lymphocyte (CD4) counts, we retrospectively assayed stored samples of the patients' plasma for antiglutamic acid decarboxylase antibody (GAD-Ab). No GAD-Ab was detected in the plasma samples of any of the three patients prior to HAART, and their CD4 counts were below 20 cells/microl at their nadir. The GAD-Ab tests became positive from 6 to 38 months after the start of HAART, and their conversion to positive followed a dramatic increase in the patients' CD4 count. Two patients developed diabetes after testing positive for GAD-Ab. Although one patient had mild diabetes prior to testing positive for GAD-Ab, the rapid worsening of glycemic control and introduction of insulin therapy almost coincided with the detection of GAD-Ab. The high magnitude of the CD4 increase during HAART and the timing of the detection of autoantibody were similar to the magnitude and timing reported in HAART-associated autoimmune thyroid disease. Autoimmune diabetes develops in some HIV-infected patients after immune restoration during HAART.