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Molecular identification of transmitted/founder viruses by single genome amplification following percutaneous occupational exposure to HIV-1

Li, H., Bar, K.J., Chen, Y., Hahn, B.H., Pfafferott, K., John, M., Mallal, S. and Shaw, G.M. (2010) Molecular identification of transmitted/founder viruses by single genome amplification following percutaneous occupational exposure to HIV-1. In: AIDS Vaccine Conference, 28 September – 1 October 2010, Altanta, USA..

Link to Published Version: https://doi.org/10.1089/aid.2010.9998
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Abstract

Background: Occupational exposure of health care workers (HCW) to HIV-1 is an uncommon but important route of virus transmission. Single genome amplification (SGA) and sequencing of plasma vRNA during acute infection (Keele PNAS 2008) makes possible, for the first time, a precise identification of transmitted/founder (T/F) viral genomes and a molecular analysis of mechanisms of treatment failure following post-exposure prophylaxis (PEP).
Methods: A 53 yo phlebotomist sustained a deep hollow-bore needle injury to the left forefinger with inadvertent blood inoculation from an advanced AIDS patient. PEP (AZT, 3TC, IND) was initiated within two hours and continued for 4 wks. 6 wks post-exposure, HIV-1 ELISA was negative. 12 wks post-exposure, HIV-1 ELISA and vRNA were positive and WB negative. SGA-direct amplicon sequencing was performed on plasma vRNA from the source patient (SP) and HCW.
Results: A total of 179 full-length pol, env gp41, and 3’ half-genome sequences were determined by SGA. Sequences from the SP revealed maximum diversity of ≤4.35% in gp41 and ≤2.19% in pol. HCW sequences revealed 12 discrete, low diversity lineages (each <0.27%) representing 12 distinct T/F viral genomes. 11 of 12 lineages showed no RT or protease drug resistance mutations. One minor lineage had 1 aa change indicative of IND resistance.
Conclusion: Transmission of ≥12 viruses following a high-risk needlestick is consistent with multivariant HIV-1 transmission observed in injection drug users (Bar J Virol 2010). Delayed viremia and Ab seroconversion, low viral sequence diversification, and absence of drug resistance mutations suggest evolutionary stasis and low or absent viral replication during PEP therapy. Mechanisms of PEP failure thus include virus sequestration and post-treatment virus reactivation.

Publication Type: Conference Item
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
URI: http://researchrepository.murdoch.edu.au/id/eprint/37488
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