Analysis of within-host HIV population evolution in patients undergoing long-term anti-retroviral therapy

Abstract

HIV remains a global public health issue because antiretroviral therapy (ART) is unable to eradicate this virus. A ’latent viral reservoir’ is responsible for a rebound in viral load if ART is interrupted. There is ongoing debate whether the viral reservoir, despite long-term antiretroviral therapy (ART), is maintained by viral replication or by clonal expansion of cells infected prior to ART. In this study, we analyzed HIV population evolution in patients undergoing long-term ART. We performed a reference-guided haplotype inference on longitudinal next generation sequencing data to reconstruct the viral population structure. The resulting haplotypes were analyzed inphylogenetic trees, and further investigated with a root-to-tip analysis. We observe signals of both viral replication and clonal expansion. However, these signals were inconsistent, which we suspectis due to reference bias