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


OBJECTIVE
Our objective was to investigate the clinical course of the development of autoantibodies and diabetes during HAART.


METHODS
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).


RESULTS
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.


CONCLUSIONS
Autoimmune diabetes develops in some HIV-infected patients after immune restoration during HAART.
Takarabe
Daisuke
D
Department of Diabetes and Metabolic Medicine, AIDS Clinical Center, National Center for Global Health and Medicine, Toyama 1-21-1, Shinjuku-ku, Tokyo 162-8655, Japan.
Rokukawa
Yuka
Y
Takahashi
Yoshihiko
Y
Goto
Atsushi
A
Takaichi
Maki
M
Okamoto
Masahide
M
Tsujimoto
Tetsuro
T
Noto
Hiroshi
H
Kishimoto
Miyako
M
Kaburagi
Yasushi
Y
Yasuda
Kazuki
K
Yamamoto-Honda
Ritsuko
R
Tsukada
Kunihisa
K
Honda
Miwako
M
Teruya
Katsuji
K
Kajio
Hiroshi
H
Kikuchi
Yoshimi
Y
Oka
Shinichi
S
Noda
Mitsuhiko
M
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D001323:Autoantibodies / Q000276:immunology; D018791:CD4 Lymphocyte Count; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male
D019380:Anti-HIV Agents; D001323:Autoantibodies