Blockade of HERG channels by HIV protease inhibitors

Blake D. Anson, Joel G R Weaver, Michael John Ackerman, Omobosola Akinsete, Keith Henry, Craig T. January, Andrew David Badley

Research output: Contribution to journalArticle

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Abstract

The HIV protease inhibitor class of antiretroviral drug causes unpredicted adverse effects by changing elements of normal cellular metabolism. A case of QT prolongation in a patient receiving protease inhibitors made us question whether these drugs might be responsible. We identified 24 patients with QT prolongation or torsade de pointes, or both, associated with protease inhibitors, using the Food and Drug Administration's voluntary adverse event reporting system. Attending physicians thought that protease inhibitors were the most probable cause of these symptoms in 14 of the patients. Drug-induced QT prolongation is usually caused by block of human ether-a-go-go-related gene (HERG) potassium channels, and we showed that lopinavir, nelfinavir, ritonavir, and saquinavir caused dose-dependent block of HERG channels heterologously expressed in HEK293 cells in vitro. We also recorded block by lopinavir of repolarising potassium current (IKr) channels in neonatal mouse cardiac myocytes. Our data show that four protease inhibitors block HERG channels, suggesting that protease inhibitors could predispose individuals to QT prolongation and torsade de pointes.

Original languageEnglish (US)
Pages (from-to)682-686
Number of pages5
JournalLancet
Volume365
Issue number9460
DOIs
StatePublished - Feb 19 2005

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HIV Protease Inhibitors
Protease Inhibitors
Ether
Lopinavir
Torsades de Pointes
Genes
Nelfinavir
Pharmaceutical Preparations
Saquinavir
Ritonavir
HEK293 Cells
Potassium Channels
United States Food and Drug Administration
Cardiac Myocytes
Potassium
Physicians

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Anson, B. D., Weaver, J. G. R., Ackerman, M. J., Akinsete, O., Henry, K., January, C. T., & Badley, A. D. (2005). Blockade of HERG channels by HIV protease inhibitors. Lancet, 365(9460), 682-686. https://doi.org/10.1016/S0140-6736(05)17950-1

Blockade of HERG channels by HIV protease inhibitors. / Anson, Blake D.; Weaver, Joel G R; Ackerman, Michael John; Akinsete, Omobosola; Henry, Keith; January, Craig T.; Badley, Andrew David.

In: Lancet, Vol. 365, No. 9460, 19.02.2005, p. 682-686.

Research output: Contribution to journalArticle

Anson, BD, Weaver, JGR, Ackerman, MJ, Akinsete, O, Henry, K, January, CT & Badley, AD 2005, 'Blockade of HERG channels by HIV protease inhibitors', Lancet, vol. 365, no. 9460, pp. 682-686. https://doi.org/10.1016/S0140-6736(05)17950-1
Anson BD, Weaver JGR, Ackerman MJ, Akinsete O, Henry K, January CT et al. Blockade of HERG channels by HIV protease inhibitors. Lancet. 2005 Feb 19;365(9460):682-686. https://doi.org/10.1016/S0140-6736(05)17950-1
Anson, Blake D. ; Weaver, Joel G R ; Ackerman, Michael John ; Akinsete, Omobosola ; Henry, Keith ; January, Craig T. ; Badley, Andrew David. / Blockade of HERG channels by HIV protease inhibitors. In: Lancet. 2005 ; Vol. 365, No. 9460. pp. 682-686.
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