ArticleJournal of virology2016
Monitoring Integration over Time Supports a Role for Cytotoxic T Lymphocytes and Ongoing Replication as Determinants of Reservoir Size.
Article in Journal of virology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Paradoxically Greater Persistence of HIV RNA-Positive Cells in Lymphoid Tissue When ART Is Initiated in the Earliest Stage of Infection.The Journal of infectious diseases · 2022Trial
- Early intervention, lasting impact: benefits of early antiretroviral therapy and implications for posttreatment control.Current opinion in HIV and AIDS · 2026Review
- HIV Cure: How Far We Have Come?Indian journal of microbiology · 2025Review
- The build-up of stock of stable integrated proviruses overtime explains the difficulty in reducing HIV-1 DNA levels when treatment is initiated at the chronic stage of the infection.Journal of virus eradication · 2023Article
- Blood Center Testing Allows the Detection and Rapid Treatment of Acute and Recent HIV Infection.Viruses · 2022Article
- Persistent low-Level viremia in persons living with HIV undertreatment: An unresolved status.Virulence · 2021Review
- Naive infection predicts reservoir diversity and is a formidable hurdle to HIV eradication.JCI insight · 2021Article
- How elite controllers and posttreatment controllers inform our search for an HIV-1 cure.The Journal of clinical investigation · 2021Review
- Persistence of an intact HIV reservoir in phenotypically naive T cells.JCI insight · 2020Article
- Cells producing residual viremia during antiretroviral treatment appear to contribute to rebound viremia following interruption of treatment.PLoS pathogens · 2020Observational
- Infrequent HIV Infection of Circulating Monocytes during Antiretroviral Therapy.Journal of virology · 2019Article
- Increasing contribution of integrated forms to total HIV DNA in blood during HIV disease progression from primary infection.EBioMedicine · 2019Article
- Longitudinal HIV sequencing reveals reservoir expression leading to decay which is obscured by clonal expansion.Nature communications · 2019Article
- Monitoring HIV DNA and cellular activation markers in HIV-infected humanized mice under cART.Virology journal · 2018Article
- The role of integration and clonal expansion in HIV infection: live long and prosper.Retrovirology · 2018Review
- Measuring integrated HIV DNA ex vivo and in vitro provides insights about how reservoirs are formed and maintained.Retrovirology · 2018Review
- Beyond the replication-competent HIV reservoir: transcription and translation-competent reservoirs.Retrovirology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
The dynamics of HIV reservoir accumulation off antiretroviral therapy (ART) is underexplored. Levels of integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) were longitudinally monitored before and after antiviral therapy. HIV integration increased over time in both elite controllers (ECs; n = 8) and noncontrollers (NCs; n = 6) before ART, whereas integration remained stable in patients on ART (n = 4). The median annual fold change was higher in NCs than in ECs and negatively correlated with CD4/CD8 T-cell ratio. Cytotoxic T lymphocyte (CTL) function as assessed by infected CD4 T-cell elimination (ICE) and granzyme B activity did not significantly change over time in ECs, suggesting that the gradual increase in integrated HIV DNA observed in ECs was not a result of progressive loss of immune-mediated control. Also, acutely infected (n = 7) but not chronically infected (n = 6) patients exhibited a significant drop in integrated HIV DNA 12 months after ART initiation. In conclusion, in the absence of ART, integrated HIV accumulates over time both in NCs and in ECs, at variable individual rates. Starting ART early in infection leads to a greater drop in integrated HIV DNA than does initiating treatment after years of infection. The increase in integrated HIV DNA over time suggests that early treatment may be of benefit in limiting HIV reservoirs. IMPORTANCE: The establishment of a latent reservoir represents a barrier to cure among HIV-infected individuals. The dynamics of HIV reservoir accumulation over time in patients before antiviral therapy is underexplored, in large part because it is difficult to accurately and reproducibly measure the size of HIV reservoir in this setting. In our study, we compared the dynamics of integrated HIV DNA over time in ECs and NCs before and after ART was initiated. We found that integrated HIV DNA levels progressively increase over time in the absence of ART, but with a higher, albeit variable, rate in NCs compared to ECs. In addition, integrated HIV DNA declines more dramatically when ART is initiated in acute rather than chronic HIV infection, suggesting important differences between acute and chronic infection. Our study highlights the role of HIV replication and CTL control in reservoir accumulation in sanctuary sites and why ART appears to be more effective in acute infection.
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