Evidence map›Paper›PMID 39160510›Full record

Observational studyJournal of biomedical science2024

Low-level HIV-1 viremia affects T-cell activation and senescence in long-term treated adults in the INSTI era.

Violeta Lara-Aguilar, Manuel Llamas-Adán, Óscar Brochado-Kith, Celia Crespo-Bermejo, Sergio Grande-García, Sonia Arca-Lafuente, Ignacio de Los Santos, Carmen Prado, Mario Alía, Coral Sainz-Pinós and 4 more

Abstract readObservational Study
In one paragraph

Observational study in Journal of biomedical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Violeta Lara-AguilarNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain. violeta.lara.aguilar@hotmail.com.ORCID http://orcid.org/0000-0003-0015-5961
Manuel Llamas-AdánNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Óscar Brochado-KithNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Celia Crespo-BermejoNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Sergio Grande-GarcíaNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Sonia Arca-LafuenteNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Ignacio de Los SantosCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain.
Carmen PradoFlow Cytometry Unit, Institute of Health Carlos III, Madrid, Spain.
Mario AlíaFlow Cytometry Unit, Institute of Health Carlos III, Madrid, Spain.
Coral Sainz-PinósNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Amanda Fernández-RodríguezNational Center of Microbiology, Institute of Health Carlos III, Madrid, Spain.
Luz Martín-CarboneroCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Institute of Health Carlos III, Madrid, Spain.
Ricardo Madrid *Complutense University, Madrid, Spain.
Verónica Briz *National Center of Microbiology, Institute of Health Carlos III, Madrid, Spain. veronica.briz@isciii.es.ORCID http://orcid.org/0000-0003-2297-5098

Funding

BioAssays S.L. MVP 32519Centro de Investigación Biomédica en Red (CIBER) en Enfermedades Infecciosas CB21/13/00044Instituto de Salud Carlos III PI18CIII/00020
6 · The paper itself

Abstract

backgroundAround 10% of people with HIV (PWH) exhibit a low-level viremia (LLV) under antiretroviral therapy (ART). However, its origin and clinical significance are largely unknown, particularly at viremias between 50 and 200 copies/mL and under modern ART based on integrase strand transfer inhibitors (INSTIs). Our aim was to characterize their poor immune response against HIV in comparison to individuals with suppressed viremia (SV) and non-HIV controls (NHC).

methodsTransversal observational study in 81 matched participants: 27 PWH with LLV, 27 PWH with SV, and 27 NHC. Activation (CD25, HLA-DR, and CD38) and senescence [CD57, PD1, and HAVCR2 (TIM3)] were characterized in peripheral T-cell subsets by spectral flow cytometry. 45 soluble biomarkers of systemic inflammation were evaluated by immunoassays. Differences in cell frequencies and plasma biomarkers among groups were evaluated by a generalized additive model for location, scale, and shape (GAMLSS) and generalized linear model (GLM) respectively, adjusted by age, sex at birth, and ART regimen.

resultsThe median age was 53 years and 77.8% were male. Compared to NHC, PWH showed a lower CD4+/CD8+ ratio and increased activation, senescence, and inflammation, highlighting IL-13 in LLV. In addition, LLV showed a downtrend in the frequency of CD8+ naive and effector memory (EM) type 1 compared to SV, along with higher activation and senescence in CD4+ and CD8+ EM and terminally differentiated effector memory RA+ (TEMRA) subpopulations. No significant differences in systemic inflammation were observed between PWH groups.

conclusionLLV between 50 and 200 copies/mL leads to reduced cytotoxic activity and T-cell dysfunction that could affect cytokine production, being unable to control and eliminate infected cells. The increase in senescence markers suggests a progressive loss of immunological memory and a reduction in the proliferative capacity of immune cells. This accelerated immune aging could lead to an increased risk of developing future comorbidities. These findings strongly advocate for heightened surveillance of these PWH to promptly identify potential future complications.

Indexed as

Cellular SenescenceHIV-1HIV InfectionsLymphocyte ActivationViremiaAdultAgedFemaleHumansMaleMiddle AgedT-LymphocytesActivationHIV-1InflammationLLVSenescence

Identifiers

PMID39160510
PMCPMC11334306

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.