title: HIV-1 DNA predicts disease progression and post-treatment virological control.
abstract: In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials.
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Williams
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hurst
authors.affiliation: Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Robinson
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Brown
authors.affiliation: Department of Sexual Health and HIV, Brighton and Sussex University Hospitals, Brighton, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Division of Infection and Immunity, School for Life Sciences, University College London, London, United Kingdom.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kinloch
authors.affiliation: The Kirby Institute of New South Wales, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Cooper
authors.affiliation: Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.affiliation: Department of Infectious Diseases, Ospedale San Raffaele, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tambussi
authors.affiliation: Division of Medicine, Wright Fleming Institute, Imperial College, London, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.affiliation: Medical Research Council Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, United Kingdom.
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.affiliation: Division of Medicine, Wright Fleming Institute, Imperial College, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.affiliation: The Kirby Institute of New South Wales, Sydney, Australia.
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.affiliation: The Kirby Institute of New South Wales, Sydney, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Phillips
authors.affiliation: Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Frater
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D003710:Demography; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D019562:Viral Load; D028761:Withholding Treatment
chemical_list: D015415:Biomarkers; D012367:RNA, Viral
keywords: HIV-1; antiretroviral therapy; cure; human; human biology; infectious disease; medicine; microbiology; primary infection; reservoir