Figure 1. For the first six months of ART, the persistent latent reservoir makes up a minority of sampled sequences.

Yellow dots show longitudinal measurements of inducible, replication-competent HIV-1 in resting CD4⁺ T cells from one patient¹⁰. Infection frequency was measured by qVOA and is reported as infectious units per million cells (IUPM). Intact, unintegrated HIV-1 DNA in recently infected cells can be detected in this assay because cellular activation stimulates completion of the viral life cycle^1,8,10. The solid-coloured regions show estimated sizes of the underlying populations that combine to yield the observed triphasic decay of IUPM. A latent reservoir (green, proportion shown at three and six months) is established before treatment and persists despite ART. This reservoir decays at a very slow rate^5,6 that can be approximated as constant over the one-year period represented here. Initially, there is a large, rapidly decaying viral population (red) that is likely to include unintegrated viral genomes. A smaller population of infected cells decays at a moderate rate (blue). Consequently, at therapy initiation, less than 0.01% of resting CD4⁺ T cells with replication-competent virus belong to the stable reservoir, while 98% belong to the large, fast-decaying population. Only after a year of therapy would the stable reservoir exceed 95%. All patients in the study showed similar decay, in which the proportion of infected cells belonging to the latent reservoir did not stabilize within the first six months of therapy¹⁰. Note that cells with infectious provirus are generally outnumbered by orders of magnitude by cells containing defective provirus. The percentages given here therefore overestimate the proportion of all sampled HIV-1 DNA that represents the persistent latent reservoir of replication-competent virus.