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Molecular mechanisms of HIV Type 1 prophylaxis failure revealed by Single-genome sequencing

Li, H., Blair, L., Chen, Y., Learn, G., Pfafferott, K., John, M., Bhattacharya, T., Hahn, B.H., Mallal, S., Shaw, G.M. and Bar, K.J. (2013) Molecular mechanisms of HIV Type 1 prophylaxis failure revealed by Single-genome sequencing. Journal of Infectious Diseases, 208 (10). pp. 1598-1603.

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Trials of HIV-1 pre- and post-exposure prophylaxis show promise. Here, we describe a novel strategy for deciphering mechanisms of prophylaxis failure that could improve therapeutic outcomes. A healthcare worker began antiretroviral prophylaxis immediately after a high-risk needlestick injury but nonetheless became viremic 11 weeks later. Single genome sequencing of plasma viral RNA identified 15 drug-sensitive transmitted/founder HIV-1 genomes responsible for productive infection. Sequences emanating from these genomes exhibited extremely low diversity, suggesting virus sequestration as opposed to low-level replication as the cause of breakthrough infection. Identification of transmitted/founder viruses allows for genome-wide assessment of molecular mechanisms of prophylaxis failure.

Item Type: Journal Article
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Oxford University Press
Copyright: © The Author 2013
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