CD8+ cells and small viral reservoirs facilitate post-ART control of SIV in Mauritian cynomolgus macaques

Harwood, O. E.; Matschke, L. M.; Moriarty, R. V.; Balgeman, A. J.; Weaver, A. J.; Ellis-Connell, A. L.; Weiler, A. M.; Winchester, L. C.; Fletcher, C. V.; Friedrich, T.; Keele, B. F.; O'Connor, D. H.; Lang, J. D.; Reynolds, M. R.; O'Connor, S. L.

doi:10.1101/2023.03.01.530655

bioRxiv · 10.1101/2023.03.01.530655

CD8+ cells and small viral reservoirs facilitate post-ART control of SIV in Mauritian cynomolgus macaques

Harwood, O. E.·Matschke, L. M.·Moriarty, R. V.·Balgeman, A. J.·Weaver, A. J.·Ellis-Connell, A. L.·Weiler, A. M.·Winchester, L. C.·Fletcher, C. V.·Friedrich, T.·Keele, B. F.·O'Connor, D. H.·Lang, J. D.·Reynolds, M. R.·O'Connor, S. L.

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Abstract

Sustainable HIV remission after antiretroviral therapy (ART) withdrawal, or post-treatment control (PTC), remains a top priority for HIV treatment. We observed surprising PTC in an MHC-haplomatched cohort of MHC-M3+ SIVmac239+ Mauritian cynomolgus macaques (MCMs) initiated on ART at two weeks post-infection (wpi). For six months after ART withdrawal, we observed undetectable or transient viremia in seven of eight MCMs. In vivo depletion of CD8+ cells induced rebound in all animals, indicating the PTC was mediated, at least in part, by CD8+ cells. We found that MCMs had smaller acute viral reservoirs than a cohort of identically infected rhesus macaques, a population that rarely develops PTC. The mechanisms by which unusually small viral reservoirs and CD8+ cell-mediated virus suppression enable PTC can be investigated using this MHC-haplomatched MCM model. Further, defining the immunologic mechanisms that engender PTC in this model may identify therapeutic targets for inducing durable HIV remission in humans.

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Harwood, O. E., Matschke, L. M., Moriarty, R. V., Balgeman, A. J., Weaver, A. J., Ellis-Connell, A. L., Weiler, A. M., Winchester, L. C., Fletcher, C. V., Friedrich, T., Keele, B. F., O'Connor, D. H., Lang, J. D., Reynolds, M. R., O'Connor, S. L.. 2023-03-02. CD8+ cells and small viral reservoirs facilitate post-ART control of SIV in Mauritian cynomolgus macaques. https://doi.org/10.1101/2023.03.01.530655

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