Discordance between HIV-1 Population in Plasma at Rebound after Structured Treatment Interruption and Archived Provirus Population in Peripheral Blood Mononuclear Cells

Hendricks, Chynna M.; Cash, Melanie N.; Tagliamonte, Massimiliano S.; Riva, Alberto; Berthou, Christian; Llano, Anuska; Salemi, Marco; Stevenson, Mario; Mavian, Carla

doi:10.1128/spectrum.01353-22

Cited by 3 publications

(3 citation statements)

References 105 publications

(132 reference statements)

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“…Multiple studies have investigated the associations between HIV reservoirs and RV, LLV, or rebound viruses after treatment interruption ( Kearney et al, 2015 ; Lu et al, 2018 ; Aamer et al, 2020 ; Liu et al, 2020 ; Cole et al, 2022 ; Hendricks et al, 2022 ). Relatively few identical sequences were detected between RV, LLV, or rebound virus and replication-competent viruses from quantitative viral outgrowth assay (QVOA) ( Bailey et al, 2006 ; Brennan et al, 2009 ; Anderson et al, 2011 ; Aamer et al, 2020 ), and in most subjects, rebound viruses and reservoir provirus did not show sequence linkages ( Bailey et al, 2006 ; Lu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy

Sun,

Zhang,

Kong

et al. 2024

Front. Microbiol.

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Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy

Sun,

Zhang,

Kong

et al. 2024

Front. Microbiol.

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show abstract

Section: Introductionmentioning

confidence: 99%

“…While the main HIV reservoir is known to be in resting memory CD4+ T-cells, several studies have shown that a fraction of viral variants, detected either in residual viremia during therapy or at rebound after therapy interruption, is genetically distinct from virus present in T-cell subsets. [3][4][5] Myeloid cells, particularly monocytes and macrophages, have been described as active reservoirs driving persistent low-level HIV expression and contributing to viral replication during rebound. [6][7][8][9][10] Monocytes are chronically activated during HIV infection, and are major mediators for the development of comorbidities related to inflammageing, and specifically cardiovascular diseases, neurocognitive disorder, and aging of the innate immune system.…”

Section: Introductionmentioning

confidence: 99%

Oral CBD treatment is associated with an anti-inflammatory gene expression signature in myeloid cells of people living with HIV

Marini

Huber

Cash

et al. 2023

Preprint

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HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least one month of CBD treatment. We collected PBMCs from three HIV-positive subjects at baseline and after CBD treatment (at least 27 days) and measured gene expression via single-cell RNA sequencing. We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells. Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment.

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Oral Cannabidiol Treatment Is Associated with an Anti-Inflammatory Gene Expression Signature in Myeloid Cells of People Living with HIV

Marini,

Huber,

Cash

et al. 2024

Cannabis and Cannabinoid Research

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Discordance between HIV-1 Population in Plasma at Rebound after Structured Treatment Interruption and Archived Provirus Population in Peripheral Blood Mononuclear Cells

Abstract: Even with effective ART, HIV-1 persists at undetectable levels and rebounds in individuals who stop treatment. Cellular and anatomical reservoirs ignite viral rebound upon treatment interruption, remaining one of the key obstacles for HIV-1 cure.

Cited by 3 publications

References 105 publications

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy

Low-level viremia episodes appear to affect the provirus composition of the circulating cellular HIV reservoir during antiretroviral therapy

Oral CBD treatment is associated with an anti-inflammatory gene expression signature in myeloid cells of people living with HIV

Oral Cannabidiol Treatment Is Associated with an Anti-Inflammatory Gene Expression Signature in Myeloid Cells of People Living with HIV

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