Background: Abacavir is an antiretroviral agent used in the treatment of HIV infection. Approximately 4% of patients receiving abacavir develop a hypersensitivity reaction, the aetiology and pathogenesis of which remain unclear. We report preliminary data on the cellular immunological profile of patients experiencing a hypersensitivity reaction to abacavir, specifically lymphocyte production of the index cytokines interferon-gamma (IFNg) and interleukin-4 (IL4) which are associated with type 1 and type 2 immune responses, respectively.
Methods: Four colour flow cytometry was used to determine frequencies of IFNg- and IL4-producing CD4 and CD8 T lymphocytes in the following HIV infected groups: (i) prior to initiation of abacavir as part of combination antiretroviral therapy (ii) six months after stable abacavir treatment and (iii) experiencing symptoms of an abacavir hypersensitivity reaction (blood samples were taken up to 48 hours following the reaction). Subjects experiencing active opportunistic infections or the use of concomitant immunomodulating agents were excluded from the study.
Results: Within the CD4 T cell compartment, increased frequencies of IL4 single positive (Th2) and IFNg+IL4+ (Th0) cells (P= 0.031 and 0.027, respectively) were observed in HSR patients, compared to those initiating abacavir without experiencing HSR. In addition, a significant reduction in IFNg single positive cells (Th1) was observed (P= 0.036). In the CD8 compartment, the frequency of both IL4 single positive (Tc2) and IFNg+IL4+ (Tc0) cells was noted (P= 0.042 and 0.018, respectively).
Conclusion: The increases in IL4-producing T cells in both the CD4 and CD8 compartments observed in patients who experienced a hypersensitivity reaction indicates a slight shift in the balance of cytokines IFNg (type 1) and IL4 (type 2) which may encourage type 2 immune responses. However, it is unclear at this stage whether the increased IL4 production is a possible causative factor in hypersensitivity. Continuing investigation will help define the precise cellular mechanisms that underlie this adverse drug reaction.
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