Evidence map›Paper›PMID 40682396›Full record

ReviewCurrent opinion in HIV and AIDS2025

A daisy chain of inferences: the role of single-cell and single-genome proviral sequencing in characterizing HIV-1 reservoirs.

Guinevere Q Lee

Abstract readReview
In one paragraph

Review in Current opinion in HIV and AIDS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

1 author.

Guinevere Q LeeWeill Cornell Medicine, Department of Medicine, Division of Infectious Diseases, New York City, USA.

Funding

REACH: Research Enterprise to Advance a Cure for HIVUM1AI164565 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI Marina Caskey, R. Brad Jones · 2021 to 2026
$32.9M
Characterization of Non-subtype B HIV-1 Reservoirs and its Association with Longitudinal Clinical OutcomesR01AI162221 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, GUINEVERE · 2021 to 2025
$2.1M
Insights into the dynamics of clonal expansion of genome-intact proviruses by examining longitudinal evolution of HIV proviral DNA compositionsR21AI150398 · NIAID · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, GUINEVERE · 2020 to 2021
$466k
NIAID NIH HHS R01 AI162221NIAID NIH HHS R21 AI150398NIAID NIH HHS UM1 AI164565
6 · The paper itself

Abstract

purpose of reviewUnderstanding and targeting the HIV reservoir requires navigating a hierarchy of inferential assays. Quantitative viral outgrowth assays, FLIP-seq, and intact proviral DNA assays (IPDA) - though methodologically distinct - are all fundamentally single-cell technologies. Each relies on limiting dilution to isolate and interrogate individual proviral genomes derived from single infected cells, offering high-resolution proxies for the outcome of greatest interest: replication competence and the risk of viral rebound. Rather than providing direct measurements, these assays infer one another in a nested framework. This review highlights the importance of critically interpreting assay outputs within this chain of inference to guide cure-directed strategies and reservoir quantification. RECENT

findingsRecent studies emphasize the complexity and limitations of current assays measuring HIV-1 reservoirs. Key themes include reliance on bioinformatics definitions of genome-intactness to infer replication competence, alongside significant limitations due to viral diversity, PCR amplification length biases, and definitional inconsistencies. Modified assays like subtype-specific IPDA aim to address these issues. SUMMARY: Standardized, subtype-specific single-cell methodologies are crucial for accurate HIV reservoir characterization. Future research should integrate large-scale sequencing with replication competence validation, and should refine bioinformatics approaches to enhance predictive accuracy. Enhanced assay precision is essential to inform effective HIV cure strategies.

Indexed as

Genome, ViralHIV-1HIV InfectionsProvirusesSingle-Cell AnalysisHumansVirus ReplicationbioinformaticsHIV reservoirproviral genome-intactnessreplication competencesingle-cell proviral sequencing

Identifiers

PMID40682396
PMCPMC12313248

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.