Chronic in vitro abacavir exposure elicits an immunological response in abacavir naive HIV positive individuals
Almeida, C., Martin, A., Nolan, D., Cameron, P., James, I., Mifsud, N., Purcell, A., McCluskey, J. and Mallal, S. (2005) Chronic in vitro abacavir exposure elicits an immunological response in abacavir naive HIV positive individuals. In: 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, 24 - 27 July 2005, Rio de Janeiro, Brazil.
INTRODUCTION: Genetic factors that lie within the Class I and Class III regions of the MHC have strong positive predictive associations with the abacavir hypersensitivity reaction in the West Australian HIV cohort. We investigated if chronic exposure to abacavir is needed to elicit an immunological response in abacavir naïve patients carrying markers of the 57.1AH.
METHODS: PBMCs from abacavir hypersensitive (n=10) and naïve (n=8) patients were cultured in the presence of the drug for 48 hours. INFγ levels were quantified by ELISAs. To elicit a priming response, PBMCs from a subset of these HIV infected abacavir naïve patients (n=4) were continuously cultured with the drug for 15 days. In addition, PBMCs from two individuals both carrying the entire 57.1AH, one from the abacavir hypersensitive group and the second an HIV-negative healthy control were also exposed to the drug for the same period.
RESULTS: INFγ levels in potentially susceptible individuals with no previous exposure to abacavir were significantly lower after a 48 hour culture in comparison to patients who had the hypersensitivity reaction (Students T-test: p=0.025). However, after chronic exposure to abacavir, 100% of HLA-B*5701-positive abacavir naïve individuals (n=3/3) had abacavir specific INFγ as did the individual who had the hypersensitivity reaction. Extracellular levels of this cytokine could not be detected in the HIV infected naïve patient who lacked HLA-B*5701 (but expressed the Class II haplospecific markers HLA-DRB1*0701 and HLA-DQ3), nor in the genetically susceptible HIV-negative individual.
CONCLUSIONS: Prior exposure to the drug is needed for the development of the hypersensitivity reaction. Chronic exposure of PBMCs from naïve patients carrying HLA-B*5701 is sufficient to mount an immune response characterised by elevated INFγ production. Our current investigations have extended to a larger patient cohort with different haplotypes since this in vitro assay may assist in the further identification of potential susceptibility factors and genetically susceptible patients.
|Publication Type:||Conference Item|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
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