The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

Abstract

BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS.The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using nextgeneration sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS.PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/ defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.

The other pandemic: lessons from 40 years of HIV research

“…However, in a small number of PLWH, a strategy for a functional cure has been raised. A recent study of viral reservoirs in individuals that contain the virus for years in the absence of antiretrovirals provided insights into endogenous mechanisms of control that could impact functional cure strategies ( 26 ). Persistent controllers (PCs) over many years had lower ratios of intact to defective viral ratios compared with those that eventually lost control, termed transient controllers (TCs).…”

“…Persistent controllers (PCs) over many years had lower ratios of intact to defective viral ratios compared with those that eventually lost control, termed transient controllers (TCs). Clonally expanded intact provirus was only found in the PC group and the provirus in the PC group was uniquely located in centromeric satellite DNA or zinc finger genes ( 26 ).…”