ArticleProceedings of the National Academy of Sciences of the United States of America2024
HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- HIV DNA and transcription before and after ART in natural controllers compared to noncontrollers.Journal of virology · 2026Article
- Virus infections and cancers: from mechanisms to therapeutics.Molecular biomedicine · 2026Review
- The elite controller phenotype.Current opinion in HIV and AIDS · 2026Review
- The TLR7 agonist vesatolimod does not measurably induce SIV expression in macaques receiving combination antiretroviral therapy initiated during chronic infection.Antimicrobial agents and chemotherapy · 2025Article
- In vivo detection of antisense HIV-1 transcripts in untreated and ART-treated individuals.Life science alliance · 2025Article
- HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Abstract
In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies toward achieving HIV remission without ART.
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