A majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation
Year: 2018
Type: article
Abstract: Antiretroviral therapy (ART) suppresses viral replication in people living with HIV. Yet, infected cells persist for decades on ART and viremia returns if ART is stopped. Persistence has been attributed to viral replication in an ART sanctuary and long-lived and/or proliferating latently infected cells. Using ecological methods and existing data, we infer that >99% of infected cells are members of clonal populations after one year of ART. We reconcile our results with observations from the first months of ART, demonstrating mathematically how a fossil record of historic HIV replication permits observed viral evolution even while most new infected cells arise from proliferation. Together, our results imply cellular proliferation generates a majority of infected cells during ART. Therefore, reducing proliferation could decrease the size of the HIV reservoir and help achieve a functional cure.
Source: Nature Communications
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Washington Research Foundation, Delaney AIDS Research Enterprise, Australian Centre for HIV and Hepatitis Virology Research, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1150034057, G1153707119, G1437275154, G1729714301, Immunoprotective Properties of Tissue-resident Memory T Cells in Mice and Humans within Mucosal Sites, G2584361871, G2910143918, DARE: Delaney AIDS Research Enterprise to find a cure., G3462701734, University of Washington Sexually Transmitted Infections Cooperative Research Cen, G4925349168, Delaney AIDS Research Enterprise to Cure HIV, G5809992656, Cell and Gene Therapy for HIV Cure, G6329780409, G6627372601, Simulating persistence and elimination of the HIV reservoir, G9000028484, NRSA Training Core, SDMC: HIV Vaccine Trials Network, University of Washington/Fred Hutch Center for AIDS Research, Host Defense Training in Allergy and Infectious Diseases, Institutional Career Development Core
OpenAlex ID: W2900567433