Lack of concordance between residual viremia and viral variants driving de novo infection of CD4(+) T cells on ART

Lack of concordance between residual viremia and viral variants driving de novo infection of CD4(+) T cells on ART

Fecha de publicación online: 02/08/2016 Revista: Retrovirology

Abstract:

Background

In most patients, current antiretroviral therapy (ART) regimens can rapidly reduce plasma viral load. However, even after years of effective treatment, a significant proportion of patients show residual plasma viremia below the clinical detection limit. Although residual viremia might be associated with increased chronic immune activation and morbidity, its origin and its potential role in the replenishment of the viral reservoir during suppressive ART is not completely understood. We performed an in-depth genetic analysis of the total and episomal cell-associated viral DNA (vDNA) repertoire in purified CD4+ T cell subsets of three HIV-infected individuals, and used phylogenetic analysis to explore its relationship with plasma viruses.

Results

The predominant proviral reservoir was established in naïve or memory (central and transitional) CD4+ T cell subsets in patients harboring X4- or R5-tropic viruses, respectively. Regardless of the viral tropism, most plasma viruses detected under suppressive ART resembled the proviral reservoir identified in effector and transitional memory CD4+ T-cell subsets in blood, suggesting that residual viremia originates from these cells in either blood or lymphoid tissue. Most importantly, sequences in episomal vDNA in CD4+ T-cells were not well represented in residual viremia.

Conclusions

Viral tropism determines the differential distribution of viral reservoir among CD4+ T-cell subsets. In spite of viral tropism, the effector and transitional memory CD4+ T-cells subsets are the main source of residual viremia during suppressive ART, even though their contribution to the total proviral pool is small. However, the lack of concordance between residual viremia and viral variants driving de novo infection of CD4+ T cells on ART may reflect the predominance of defective plasma HIV RNA genomes. These findings highlight the need for monitoring the multiple viral RNA/DNA persistence markers, based on their differential contribution to viral persistence.

Keywords

HIV-1 Viral reservoir Residual viremia Persistence CD4+ T cell subsets

Autores: Puertas MC, Noguera-Julian M, Massanella M, Pou C, Buzon MJ, Clotet B, Stevenson M, Paredes R, Blanco J, Martinez-Picado J.

Suscríbete a la newsletter

Back to Top
Irsi Caixa

Impulsado por:

Fundación 'La Caixa' Generalitat de Catalunya - Departament de Salut

 

HR Excellence in Research

Miembro de:

Cerca

Con la colaboración de: