Molecular Mechanisms of HIV-1 Prophylaxis Failure Revealed by Single Genome Sequencing

Trials of HIV-1 preand 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. at M uoch U niersity on D ecem er 1, 2013 http://jidrdjournals.org/ D ow nladed from