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HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions

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Abstract

HIV infection results in severe immune dysfunction with ensuing sequelae that includes characteristic opportunistic infections. Pneumocystis pneumonia (PCP) is one of the most common of these infections and is routinely treated with sulphamethaxazole (SMX). Although this drug is known to cause hypersensitivity adverse drug reactions (ADRs) in 0.1% of the general population, the incidence of these ADRs increases tenfold in the HIV-positive population. The HIV-1 trans-activator of transcription (HIV-1 Tat) together with the drug metabolite sulphamethaxazole-hydroxylamine (SMX-HA) have both been reported to be factors in these hypersensitivity ADRs. In this study, we use an inducible, Tat-expressing vector system to show that the level of Tat expression contributes to the cellular sensitivity of Jurkat T cells to SMX-HA. We further demonstrated that apoptosis is the likely mechanism by which this occurs. Thus, our data provide insight into the significant increase of SMX-related ADRs during the transition between HIV-1 infection and AIDS.

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Acknowledgments

This work was supported by grants from the Canadian Institutes for Health Research (CIHR) and the CIHR-GSK Chair in Paediatric Clinical Pharmacology (to M.J.R.) and a CHIR Canada Graduate Scholarships Doctoral Award (to K.A.).

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Authors and Affiliations

  1. Biotherapeutics Research Group, Robarts Research Institute, 100 Perth Drive, London, ON, Canada, N6A 5K8

    Kemi Adeyanju, Adriana Krizova, Philippe A. Gilbert, Gregory A. Dekaban & Michael Rieder

  2. Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada, N6A 5K8

    Kemi Adeyanju, Philippe A. Gilbert & Gregory A. Dekaban

  3. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada, N6A 5K8

    Adriana Krizova & Michael Rieder

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  1. Kemi Adeyanju
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  2. Adriana Krizova
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  3. Philippe A. Gilbert
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  4. Gregory A. Dekaban
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Correspondence to Gregory A. Dekaban or Michael Rieder.

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Kemi Adeyanju and Adriana Krizova contributed equally to this article.

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Adeyanju, K., Krizova, A., Gilbert, P.A. et al. HIV Tat potentiates cell toxicity in a T cell model for sulphamethoxazole-induced adverse drug reactions. Virus Genes 38, 372–382 (2009). https://doi.org/10.1007/s11262-009-0344-3

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