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Genomic landscape of HIV-1 proviruses in ART-treated immunological non-responders
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DOI：10.3389/fimmu.2026.1804632.png)
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Abstract
En 中文
BackgroundImmunological non-responders (INRs) and immunological responders (IRs) exhibit distinct patterns of immune reconstitution despite suppressive antiretroviral therapy (ART); however; the genetic characteristics of the HIV-1 reservoir in these groups remain poorly understood. This study investigates the landscape of HIV-1 proviruses in INRs and IRs; and its potential association with immune reconstitution.MethodsPeripheral blood mononuclear cells (PBMCs) from 10 ART-treated INRs and 10 IRs were analyzed using near-full-length HIV-1 DNA amplification and PacBio third-generation sequencing to characterize genetically intact and defective proviral genomes. Intact open reading frames (ORFs) were further inferred using the CFEIntact tool.ResultsCompared with IRs; INRs had a higher total proviral genome per 106 PBMCs; although the difference did not reach statistically significance. INRs also displayed a significantly higher level of intact proviral genomes per 106 PBMCs and a trend toward a higher proportion of intact sequences. Defective proviruses remained the predominant component of the reservoir in both groups and were broadly comparable in number and composition. In both cohorts; proviral defects were more frequently observed in the 3′ half of the genome.DiscussionOur study reveals a distinct proviral landscape in ART-treated INRs; characterized by elevated levels of intact proviral genomes. These observations suggest that the intact component of the reservoir may represent a clinically relevant feature of incomplete immune reconstitution; and provide a rationale for further studies of reservoir-directed interventions in this population.
Keywords:
immunological non-responders
HIV reservoir
intact and defective provirus
near full-length sequencing
proviral integrity
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