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Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

By Panagiota Zacharopoulou, Emanuele Marchi, Ane Ogbe, Nicola Robinson, Helen Brown, Mathew Jones, Lucia Parolini, Matthew Pace, Nicholas Grayson, Pontiano Kaleebu, Helen Rees, Sarah Fidler, Philip Goulder, Paul Klenerman, John Frater

Posted 24 Nov 2020
bioRxiv DOI: 10.1101/2020.11.24.395574

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without evidence of viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Twelve individuals who had received 12 months of ART from primary HIV infection and then undertook a TI were sampled at the time of stopping therapy. Using RNA-Seq we explored gene expression in CD4 T cells to look for evidence of a mechanism that might underpin virological rebound and lead to discovery of an associated biomarker. Using independent analysis tools, genes associated with the type I interferon response were strongly associated with a delayed time to viral rebound following TI. These are the first data we are aware of that link transcriptomic signatures associated with innate immunity with control following TI. While these results need to be confirmed in larger trials, they could help define a strategy for new therapies and identify new biomarkers for remission.

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