ArticlePLoS pathogens2021
Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 50 citations in OpenAlex.
- Interleukin 6 Blockade With Tocilizumab Diminishes Indices of Inflammation That Are Linked to Mortality in Treated Human Immunodeficiency Virus Infection.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- The immunophenotype and proviral landscape of HIV-infected CD4 T cells during antiretroviral therapy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Clonal dynamics of HIV-infected and uninfected T cells.EBioMedicine · 2026Article
- Single-cell profiling reveals immunometabolic remodeling with T-cell dysfunction in HIV-1 infected people.Infectious diseases & immunity · 2026Article
- HIV-seq reveals gene expression differences between HIV-transcribing cells from viremic and suppressed people with HIV.Nature communications · 2026Article
- RhCMV expands CCR5+ memory T cells and promotes SIV reservoir seeding in the gut mucosa.JCI insight · 2026Article
- Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort.Viruses · 2025Article
- The impact of acute stress on the HIV reservoir: a prospective interventional trial.Journal of virus eradication · 2025Article
- Changes in HIV-1 Reservoir Dynamics After Mpox Infection.Journal of medical virology · 2025Article
- Mild HIV-specific selective forces overlaying natural CD4+ T cell dynamics explain the clonality and decay dynamics of HIV reservoir cells.Cell systems · 2025Article
- Novel insights into immune checkpoints in HIV/SHIV infection: from SHIVJournal of virology · 2025Article
- Applications and limitations of the passenger hypothesis for HIV reservoir persistence and cure.Journal of virology · 2025Review
- Selective decline of intact HIV reservoirs during the first decade of ART followed by stabilization in memory T cell subsets.AIDS (London, England) · 2025Article
- Divergent populations of HIV-infected naive and memory CD4+ T cell clones in children on antiretroviral therapy.The Journal of clinical investigation · 2025Article
- Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?Biomolecules · 2025Review
- Blood and tissue HIV-1 reservoirs display plasticity and lack of compartmentalization in virally suppressed people.Nature communications · 2025Article
- Establishment and evaluation of a predictive model for immune reconstitution in people living with HIV after antiretroviral therapy.BMC infectious diseases · 2025Article
- Phenotyping Viral Reservoirs to Reveal HIV-1 Hiding Places.Current HIV/AIDS reports · 2025Review
- Double, double toil and trouble: transforming growth factor beta (TGF-β) in HIV infection.Frontiers in immunology · 2025Review
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 2 countries.
Funding
Abstract
The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.
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