The following is a summary of “IMPACT OF HIV RESERVOIR IN THE LOSS OF NATURAL ELITE CONTROL OF HIV-1 INFECTION”, presented by Carmen Gasca-Capote, Xiaodong Lian, Ce Gao, Isabelle C. Roseto, Maria de los Reyes Jimenez-Leon, Gregory Gladkov, Alberto Perez-Gomez, Nuria Espinosa, Francesc Vidal, Antonio Rivero, Luis Fernando Lopez-Cortes, Xu G. Yu, Mathias Lichterfeld, Ezequiel Ruiz-Mateos.

As much as 25% of elite controllers (EC) experience a loss of virological control. This has led to the classification of EC into 2 categories: “transient elite controllers” (TC), who eventually lose viremia control, and “persistent controllers” (PC), who maintain viremia control forever over time. In order to advance new pathways in HIV curative techniques, it is crucial to determine the causes of HIV disease progression. Differentiating between PC and TC requires a thorough characterization of the quality of HIV reservoirs, despite the fact that numerous studies have revealed that PC and TC offer distinct immunological, proteomic, metabolomic, and miRNA profiles.

The peripheral blood mononuclear cells (PBMCs) of 41 individuals who had been on antiretroviral therapy for a median of 9 years (2-19 years) were used to isolate genomic DNA from 18 PC (viremia control for more than 23 years), 10 TC (sustained viral load above the detection limit, more than 40 HIV RNA copies/mL, during more than 1 year of follow-up) before losing the control (0.3-2 years), and 0 individuals. Next-generation sequencing methods, including full-length individual proviral sequencing (FLIPseq) and matching integration site and proviral sequencing, were then applied to characterize the HIV-1 reservoir (MIP-seq). Total, intact, and faulty provirus levels were considerably lower in PC and TC patients than in those receiving ART. Total provirus numbers did not change significantly between PC and TC, although a tendency toward a greater proportion of faulty proviruses was seen in TC (P=0.072).

Intact provirus fraction was substantially higher in TC than in PC (P=0.005). Moreover, a greater variety of viruses, as demonstrated by the discovery of intact proviruses in TC that had not been clonally grown, was observed in TC as compared to PC. By contrast, in PC, the entire proviruses were found in centromeric satellite DNA or zinc-finger genes, both of which are associated with heterochromatin characteristics. Proviral reservoir topography in peripheral blood mononuclear cells varied between people with PC, TC, and those receiving ART. In contrast to the persistent controllers, whose undamaged proviruses were preferentially integrated in non-genic or pseudogenic areas, those of TC and ART-treated individuals were situated in genic regions.