ArticleScientific reports2023
Application of ultrasensitive digital ELISA for p24 enables improved evaluation of HIV-1 reservoir diversity and growth kinetics in viral outgrowth assays.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Isolation of Brain Microglia to Study Persistence of Human Immunodeficiency Virus-1.Journal of visualized experiments : JoVE · 2026Article
- Development of a hypersensitive digital ELISA system for hepatitis B core antigen.Analytical and bioanalytical chemistry · 2026Article
- Article
- Emerging Vector-Borne Nipah Virus Infection: Unexplored Hazards, Diagnostic Challenges, and the Potential of Phytomedicine-Based Therapeutics.Current pharmaceutical design · 2026Review
- Production of virus-like particles with AsCas12a nuclease and CMV-driven crRNA for mammalian genome editing.Frontiers in genome editing · 2026Article
- Comparison of manual and automated ultrasensitive assays for residual HIV-1 in plasma from individuals on suppressive antiretroviral therapy.Journal of clinical microbiology · 2025Article
- Ultra-low level HIV p24 drives immune activation in antiretroviral therapy-treated people living with HIV.Communications medicine · 2025Article
- An Immunocytochemistry Method to Investigate the Translationally Active HIV Reservoir.International journal of molecular sciences · 2025Article
- Compact Digital Immunoassay Platform Integrating ELISA with a Lateral Flow Strip.Biomedicines · 2024Article
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
The advent of combined antiretroviral therapy (cART) has been instrumental in controlling HIV-1 replication and transmission and decreasing associated morbidity and mortality. However, cART alone is not able to cure HIV-1 due to the presence of long-lived, latently infected immune cells, which re-seed plasma viremia when cART is interrupted. Assessment of HIV-cure strategies using ex vivo culture methods for further understanding of the diversity of reactivated HIV, viral outgrowth, and replication dynamics are enhanced using ultrasensitive digital ELISA based on single-molecule array (Simoa) technology to increase the sensitivity of endpoint detection. In viral outgrowth assays (VOA), exponential HIV-1 outgrowth has been shown to be dependent upon initial virus burst size surpassing a critical growth threshold of 5100 HIV-1 RNA copies. Here, we show an association between ultrasensitive HIV-1 Gag p24 concentrations and HIV-1 RNA copy number that characterize viral dynamics below the exponential replication threshold. Single-genome sequencing (SGS) revealed the presence of multiple identical HIV-1 sequences, indicative of low-level replication occurring below the threshold of exponential outgrowth early during a VOA. However, SGS further revealed diverse related HIV variants detectable by ultrasensitive methods that failed to establish exponential outgrowth. Overall, our data suggest that viral outgrowth occurring below the threshold necessary for establishing exponential growth in culture does not preclude replication competence of reactivated HIV, and ultrasensitive detection of HIV-1 p24 may provide a method to detect previously unquantifiable variants. These data strongly support the use of the Simoa platform in a multi-prong approach to measuring latent viral burden and efficacy of therapeutic interventions aimed at an HIV-1 cure.
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