Abstract
Mechanisms underlying durable control of HIV after antiretroviral therapy interruption remain poorly understood. Here we provide a comprehensive longitudinal analysis in a non-human primate model of post-treatment control using SIVmac251-infected male cynomolgus macaques (pVISCONTI study). Controllers exhibit lower levels of SIV DNA, intact proviruses, transcriptional activity, and viral evolution compared to non-controllers in blood and tissues long after therapy interruption. Before interruption, controllers already have fewer intact proviruses in lymph nodes, and this difference persists in blood shortly after interruption, prior to viral rebound. Intact provirus levels in lymph nodes before interruption negatively correlate with CD8⁺ T-cell capacity to suppress SIV and reflect rebound magnitude. The study demonstrates that markers of post-treatment control are detectable in lymph nodes before therapy interruption and in blood shortly after, and suggests that host immune responses may shape intact provirus profiles during treatment.
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Data availability
Sequencing data generated in this study (proviral DNA sequences from tissue samples collected at euthanasia and plasma viral RNA sequences from longitudinal timepoints) have been deposited in the Sequence Read Archive (SRA) under BioProject accession code PRJNA1256680 [http://www.ncbi.nlm.nih.gov/bioproject/1256680]. Basecalled FASTQ files are provided for all runs. Metadata for each macaque, tissue type and timepoints are included in the associated BioSamples. Additionnaly, the data that support the findings of this study are presented in the main figures and Supplementary Information/Source Data files. Source data are provided with this paper. Further information and requests for resources and reagents should be directed to the lead contact. Request for biological resources will be fulfilled based on availability and upon the establishment of an MTA. Source data are provided with this paper.
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Acknowledgements
This study was funded by MSDAvenir though a research grant to the ANRS-RHIVIERA consortium, and the ANRS | Emerging infectious diseases French agency. A.M., E.G., and M.F. were supported by ANRS. IDMIT was supported by ANR French agency under references ANR-11-INBS-0008 and ANR-10-EQPX-02-01. We thank animal care workers, in particular Sebastien Langlois, Benoit Delache, Clare-Maelle Fovet, Maxime Pottier, Jean-Marie Robert as well as Julie Morin, Laetitia Bossevot, Brice Targat, Wesley Gros, Marco Leonec for expert technical assistance and Isabelle Mangeot-Méderlé for helpful project management at IDMIT. FTC, DTG, and TDF were obtained from Gilead and ViiV Healthcare through the “IAS Towards an HIV Cure” common Material Transfer Agreement. The SIV1C cell line was kindly provided by François Villinger.
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C.R., R.L.G., and A.S.C. designed the pVISCONTI program with the contribution of D.D., O.L., M.M.T., N.D.B., and V.A.F. C.R. and V.A.F. designed the virological study of this program. C.R., R.L.G, A.S.C., and V.A.F. obtained funding. C.C., A.M, A.Mi., and V.A.F. designed the experiments. C.C., A.M., E.G., D.D., C.P., A.Mi., M.F., N.D., V.M., and N.D.B. carried out the experiments. C.C., A.M., A.C., E.G., D.D., C.P., A.Mi, M.F., N.D., V.M., N.D.B., R.L.G., A.S.C., and V.A.F. analyzed the data. C.C., A.M., A.C., M.M.T., C.R., R.L.G., A.S.C., and V.A.F. interpreted the results. V.A.F. supervised the study. C.C. and V.A.F. wrote the manuscript with assistance from A.M. All authors critically reviewed the manuscript and contributed to the final version.
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C.C. honoraria and travel grants from MSD, ViiV Healthcare and Gilead Sciences for participation in educational programs and conferences. A.S.C. has received speaker fees from MSD, ViiV Healthcare, Gilead, Janssen. V.A.F. has received grants (to her institution) from ViiV Healthcare and honoraria and travel grants from ViiV Healthcare and Gilead Sciences for participation in educational programs and conferences. The other authors declare no competing interests.
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Charre, C., Melard, A., Chaillon, A. et al. Post-treatment SIV control is associated with specific features of viral persistence before and after treatment interruption. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69720-6
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DOI: https://doi.org/10.1038/s41467-026-69720-6
