Evidence map›Paper›PMID 41331331›Full record

ArticleCommunications medicine2025

Ultra-low level HIV p24 drives immune activation in antiretroviral therapy-treated people living with HIV.

Enrico Richter, Julia König, Antonia Büning, Theresa Bechtel, Andrea Casado, Jernej Pušnik, Trevor A Crowell, Heiko Jessen, Jürgen K Rockstroh, Christoph Boesecke and 3 more

Abstract read
In one paragraph

Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
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

13 authors.

Enrico RichterInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany. enrico.richter@ukbonn.de.ORCID http://orcid.org/0009-0008-7736-8053
Julia KönigInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Antonia BüningInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Theresa BechtelInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Andrea CasadoInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.
Jernej PušnikInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-5987-8606
Trevor A CrowellU.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0001-5947-265X
Heiko JessenInfectiology Berlin MVZ (Praxis Jessen² + Colleagues), Berlin, Germany.
Jürgen K RockstrohGerman Center for Infection Research (DZIF), partner site Bonn-Cologne, Braunschweig, Germany.ORCID http://orcid.org/0000-0003-2858-3888
Christoph BoeseckeGerman Center for Infection Research (DZIF), partner site Bonn-Cologne, Braunschweig, Germany.
Stefan EsserHPSTD HIV Outpatient Clinic, Department of Dermatology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Christoph StephanDepartment of Internal Medicine 2, Infectious Diseases Unit, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.ORCID http://orcid.org/0000-0003-3777-9006
Hendrik StreeckInstitute of Virology, University Hospital Bonn, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0002-0335-6390

Funding

Henry M. Jackson Foundation (Henry M. Jackson Foundation for the Advancement of Military Medicine) #HT94252430004
6 · The paper itself

Abstract

backgroundDespite effective antiretroviral therapy (ART), people living with HIV (PLWH) often exhibit persistent immune activation, the mechanisms of which remain unclear. Increasing evidence suggests that residual low-level viremia and ongoing viral protein expression may persist even under long-term suppressive ART, underscoring the need for a better understanding of residual HIV persistence.

methodsWe therefore optimized a digital single-molecule array (Simoa®) technology to detect ultra-low levels of HIV p24 antigen in plasma, achieving femtogram sensitivity. In addition, we used flow cytometry to analyze HIV-specific T cell responses.

resultsHere we show that in a cohort of 108 participants with chronic HIV on long-term ART with HIV-1 RNA < 30 copies/mL for >4 years, p24 is detectable (17 - 370 fg/mL) in 42. Dual protease inhibitor therapy is associated with significantly lower p24 levels (p  <  0.05), while age, ART duration or CD4/CD8 ratio show no effect. Monitoring 41 individuals who initiated ART during acute HIV, p24 remains detectable in 20% after two years. Although p24 correlates with viral RNA early in ART (r = 0.83, p < 0.0001), this association is lost after two months (r = 0.20, p = 0.21). Importantly, p24+ individuals show significantly higher frequencies of PD-1 + , CD38 + , and CD38 + HLA-DR + CD8 T cells (p  <  0.01; p  <  0.05), alongside enhanced TNF-α and CD107a responses to HIV Gag (p  <  0.01; p  <  0.05).

conclusionsTo best of our knowledge, our findings provide the first large-cohort evidence of low-level p24 persistence during suppressive ART and suggest that ongoing p24 production may contribute to residual immune activation in treated PLWH.

Identifiers

PMID41331331
PMCPMC12672821

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.