Quantifying the clonality and dynamics of the within-host HIV-1 latent reservoir

Abstract Among people living with human immunodeficiency virus type 1 (HIV-1), the long-term persistence of a population cells carrying transcriptionally silent integrated viral DNA (provirus) remains primary barrier to developing an effective cure. Ongoing cell division via proliferation is generally considered be driving force behind this latent HIV-1 reservoir. The contribution mechanism (clonal expansion) supported by observation that proviral sequences sampled from reservoir are often identical. This outcome quantified as ‘clonality’ sample population, e.g. fraction provirus observed more than once. However, clonality quantitative measure inconsistently defined and its statistical properties not well understood. In Reflections article, we use mathematical phylogenetic frameworks formally examine inherent problems using characterize dynamics composition We describe how adequate for task due complexity infected ‘labeled’ sequences—the sampling process evolutionary history active replication before treatment—as variation in birth death rates among lineages over time. Lastly, outline potential directions research address these issues.