A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation
A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation
Abstract Antiretroviral therapy (ART) suppresses viral replication in people living with HIV. Yet, infected cells persist for decades on ART. When ART is stopped, HIV replication resumes allowing progression to AIDS. HIV might persist by replicating in drug sanctuaries where ART concentrations are insufficient. Alternatively, latently infected T cells may proliferate. To infer the dominant mechanism, we characterized the relative abundance of unique sequences in ART suppressed individuals. We show that >99% of infected cells are clonal after 1 year of ART, implying cellular proliferation as the primary generator of infected cells. Using a mathematical model, we demonstrate that even if the largest plausible drug sanctuary is assumed, within 6 months of ART nearly all infected cells arise from proliferation rather than HIV replication. Targeting cellular proliferation could reduce the size of the HIV reservoir.
Duke Elizabeth R.、Wagner Thor A.、Schiffer Joshua T.、Spivak Adam M.、Reeves Daniel B.、Palmer Sarah E.
Fred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division||University of Washington, Department of MedicineUniversity of Washington, Department of Pediatrics||Seattle Children?ˉs Research InstituteFred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases Division||University of Washington, Department of Medicine||Fred Hutchinson Cancer Research Center, Clinical Research DivisionUniversity of Utah School of Medicine, Department of MedicineFred Hutchinson Cancer Research Center, Vaccine and Infectious Diseases DivisionUniversity of Sydney, The Westmead Institute for Medical Research
医药卫生理论医学研究方法基础医学
Duke Elizabeth R.,Wagner Thor A.,Schiffer Joshua T.,Spivak Adam M.,Reeves Daniel B.,Palmer Sarah E..A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/146977.点此复制
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