Reservoir and Phylogenetic Signatures Identify Distinct Subsets of HIV-1 Nonsuppressible Viremia

Abstract In nonsuppressible HIV viremia (NSV), individuals have persistently detectable viral load despite adherence to ≥2 fully active antiretroviral drugs. NSV represents an area of clinical uncertainty and an opportunity to understand the mechanisms of HIV persistence. We performed in-depth virologic characterization to identify distinct NSV phenotypes. We categorized participants into those who had persistent viremia after antiretroviral therapy (ART) initiation (primary NSV) and those who had NSV after a period of virologic suppression (secondary NSV). Despite the prolonged viremia, there was no significant evidence of active viral evolution in either the primary or secondary NSV groups. Primary NSV participants had >10-fold higher levels of intact proviral DNA by the intact proviral DNA assay ( P