Genomic landscape of HIV-1 proviruses in ART-treated immunological non-responders

ST Shengquan Tang †

doi:10.3389/fimmu.2026.1804632

Genomic landscape of HIV-1 proviruses in ART-treated immunological non-responders

2026-08-12

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OA

AI

S

ST Shengquan Tang †

Y

YW Yue Wang †

Y

YL Yanqiu Lu

Z

ZT Zhen Tong

J

JG Jiahui Guo

Y

YC Yizhi Cui

V

VH Vijay Harypursat

Y

YC Yemiao Chen

J

JO Jing Ouyang

H

HL Huan Li

T

TW Tong Wang *

Q

QZ Quanhua Zhou *

Y

YC Yaokai Chen *

DOI：10.3389/fimmu.2026.1804632

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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

Genomic landscape of HIV-1 proviruses in ART-treated immunological non-responders

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