ArticleAIDS (London, England)2019
Genetic complexity in the replication-competent latent HIV reservoir increases with untreated infection duration in infected youth.
Article in AIDS (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Advancements in single-cell techniques for examining the HIV reservoir: pathways to a cure.mBio · 2025Review
- A Canadian Survey of Research on HIV-1 Latency-Where Are We Now and Where Are We Heading?Viruses · 2024Review
- Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains.PLoS pathogens · 2022Article
- Review
- HIV proviral genetic diversity, compartmentalization and inferred dynamics in lung and blood during long-term suppressive antiretroviral therapy.PLoS pathogens · 2022Article
- Genotypic and Phenotypic Diversity of the Replication-Competent HIV Reservoir in Treated Patients.Microbiology spectrum · 2022Article
- Article
- Naive infection predicts reservoir diversity and is a formidable hurdle to HIV eradication.JCI insight · 2021Article
- Characterizing the Relationship Between Neutralization Sensitivity andFrontiers in immunology · 2021Article
- HIV Diversity and Genetic Compartmentalization in Blood and Testes during Suppressive Antiretroviral Therapy.Journal of virology · 2019Article
- Clinical and evolutionary consequences of HIV adaptation to HLA: implications for vaccine and cure.Current opinion in HIV and AIDS · 2019Review
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveTimely initiation of combination antiretroviral therapy (ART) limits latent HIV reservoir size and should also limit reservoir genetic complexity. However, the relationship between these two factors remains unclear, particularly among HIV-infected youth.
designRetrospective analysis of replication-competent latent HIV clones serially isolated by limiting-dilution culture from resting CD4 T-cell reservoirs from ART-suppressed, young adult participants of a historic phase I therapeutic vaccine trial (PACTG/IMPAACT-P1059).
methodsReplication-competent latent HIV clones isolated from resting CD4 T cells of four perinatally and 10 nonperinatally infected young adults (average 22 versus 6 years uncontrolled infection, respectively) were sequenced in Pol and Nef. Within-host HIV sequence datasets were characterized with respect to their genetic diversity and inferred immune escape mutation burden.
resultsAlthough participants were comparable in terms of sociodemographic and HIV sampling characteristics (e.g. on average, a mean 17 Pol sequences were recovered at five timepoints over up to 70 weeks) and the length of ART suppression at study entry (average 3 years), replication-competent HIV reservoir size, genetic diversity, immune escape mutation burden and variant complexity were significantly higher among the perinatally infected participants who experienced longer durations of uncontrolled viremia. Nevertheless, viral sequences inferred to retain susceptibility to host cellular immune responses were detected in all participants, irrespective of uncontrolled viremia duration.
conclusionHIV elimination in late-suppressed youth may be doubly challenged by larger and more genetically complex reservoirs. Strategies that integrate host and viral genetic complexity to achieve HIV remission or cure may merit consideration in such cases.
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