Complex decay dynamics of HIV virions, intact and defective proviruses, and 2LTR circles following initiation of antiretroviral therapy

In persons living with HIV-1 (PLWH) who start antiretroviral therapy (ART), plasma virus decays in a biphasic fashion to below the detection limit. The first phase reflects the short half-life (<1 d) of cells that produce most of the plasma virus. The second phase represents the slower turnover (t(1/2) = 14 d) of another infected cell population, whose identity is unclear. Using the intact proviral DNA assay (IPDA) to distinguish intact and defective proviruses, we analyzed viral decay in 17 PLWH initiating ART. Circulating CD4(+) T cells with intact proviruses include few of the rapidly decaying first-phase cells. Instead, this population initially decays more slowly (t(1/2) = 12.9 d) in a process that largely represents death or exit from the circulation rather than transition to latency. This more protracted decay potentially allows for immune selection. After similar to 3 mo, the decay slope changes, and CD4(+) T cells with intact proviruses decay with a half-life of 19 mo, which is still shorter than that of the latently infected cells that persist on long-term ART. Two-long-terminal repeat (2LTR) circles decay with fast and slow phases paralleling intact proviruses, a finding that precludes their use as a simple marker of ongoing viral replication. Proviruses with defects at the 50 or 30 end of the genome show equivalent monophasic decay at rates that vary among individuals. Understanding these complex early decay processes is important for correct use of reservoir assays and may provide insights into properties of surviving cells that can constitute the stable latent reservoir.

Automated summary

This study analyzed the viral decay process in HIV-infected individuals receiving ART and distinguished intact and defective proviruses using IPDA. The findings showed that CD4(+) T cells with intact proviruses decayed slower initially and then accelerated after a few months. 2LTR circles could not be used as a simple marker for ongoing viral replication. The rate of decay varied among individuals with different defect positions in the genome. Understanding these decay processes is crucial for accurate assessment of the viral reservoir and provides insights into the characteristics of surviving cells.