title: Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs.
abstract: Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure.
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Malatinkova
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Ward
authors.identifier: http://orcid.org/0000-0003-2097-8439
authors.initials: W
authors.lastname: De Spiegelaere
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Pawel
authors.initials: P
authors.lastname: Bonczkowski
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Maja
authors.initials: M
authors.lastname: Kiselinova
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vervisch
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Trypsteen
authors.affiliation: Division of Infection and Immunity, Royal Free Hospital, London, United Kingdom.
authors.forename: Margaret
authors.initials: M
authors.lastname: Johnson
authors.affiliation: AIDS Reference Laboratory, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Verhofstede
authors.affiliation: Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Danny
authors.initials: D
authors.lastname: de Looze
authors.affiliation: Department of Gastroenterology, Royal Free Hospital, London, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Murray
authors.affiliation: Division of Infection and Immunity, Royal Free Hospital, London, United Kingdom.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kinloch-de Loes
authors.affiliation: HIV Translational Research Unit, Department of Internal Medicine, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Linos
authors.identifier: http://orcid.org/0000-0002-8600-1631
authors.initials: L
authors.lastname: Vandekerckhove
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001769:Blood / Q000821:virology; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification; D012007:Rectum / Q000821:virology; D055502:Secondary Prevention; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents
keywords: HIV-1 reservoir; early long-term ART; human; infectious disease; long-term non-progressors; microbiology; seroconversion; viruses